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System architects are often impatient about the future, especially when they can see something good coming down the pike. And thus, we can expect a certain amount of healthy and excited frustration when it comes to the Compute Express Link, or CXL, interconnect created by Intel, which with the absorption of Gen-Z technology from Hewlett Packard Enterprise and now OpenCAPI technology from IBM will become the standard for memory fabrics across compute engines for the foreseeable future.
The CXL 2.0 specification, which brings memory pooling across the PCI-Express 5.0 peripheral interconnect, will soon available on CPU engines. Which is great. But all eyes are already turning to the just-released CXL 3.0 specification, which rides atop the PCI-Express 6.0 interconnect coming in 2023 with 2X the bandwidth, and people are already contemplating what another 2X of bandwidth might offer with CXL 4.0 atop PCI-Express 7.0 coming in 2025.
In a way, we expect for CXL to follow the path blazed by IBM’s “Bluelink” OpenCAPI interconnect. Big Blue used the Bluelink interconnect in the “Cumulus” and “Nimbus” Power9 processors to provide NUMA interconnects across multiple processors, to run the NVLink protocol from Nvidia to provide memory coherence across the Power9 CPU and the Nvidia “Volta” V100 GPU accelerators, and to provide more generic memory coherent links to other kinds of accelerators through OpenCAPI ports. But the path that OpenCAPI and CXL will not be exactly the same, obviously. OpenCAPI is kaput and CXL is the standard for memory coherence in the datacenter.
IBM put faster OpenCAPI ports on the “Cirrus” Power10 processors, and they are used to provide those NUMA links as with the Power9 chips as well as a new OpenCAPI Memory Interface that uses the Bluelink SerDes as a memory controller, which runs a bit slower than a DDR4 or DDR5 controller but which takes up a lot less chip real estate and burns less power – and has the virtue of being exactly like the other I/O in the chip. In theory, IBM could have supported the CXL and NVLink protocols running atop its OpenCAPI interconnect on Power10, but there are some sour grapes there with Nvidia that we don’t understand – it seems foolish not to offer memory coherence with Nvidia’s current “Ampere” A100 and impending “Hopper” H100 GPUs. There may be an impedance mismatch between IBM and Nvidia in regards to signaling rates and lane counts between OpenCAPI and NVLink. IBM has PCI-Express 5.0 controllers on its Power10 chips – these are unique controllers and are not the Bluelink SerDes – and therefore could have supported the CXL coherence protocol, but as far as we know, Big Blue has chosen not to do that, either.
Given that we think CXL is the way a lot of GPU accelerators and their memories will link to CPUs in the future, this strategy by IBM seems odd. We are therefore nudging IBM to do a Power10+ processor with support for CXL 2.0 and NVLink 3.0 coherent links as well as with higher core counts and maybe higher clock speeds, perhaps in a year or a year and a half from now. There is no reason IBM cannot get some of the AI and HPC budget given the substantial advantages of its OpenCAPI memory, which is driving 818 GB/sec of memory bandwidth out of a dual chip module with 24 cores. We also expect for future datacenter GPU compute engines from Nvidia will support CXL in some fashion, but exactly how it will sit side-by-side with or merge with NVLink is unclear.
It is also unclear how the Gen-Z intellectual property donated to the CXL Consortium by HPE back in November 2021 and the OpenCAPI intellectual property donated to the organization steering CXL by IBM last week will be used to forge a CXL 4.0 standard, but these two system vendors are offering up what they have to help the CXL effort along. For which they should be commended. That said, we think both Gen-Z and OpenCAPI were way ahead of CXL and could have easily been tapped as in-node and inter-node memory and accelerator fabrics in their own right. HPE had a very elegant set of memory fabric switches and optical transceivers already designed, and IBM is the only CPU provider that offered CPU-GPU coherence across Nvidia GPUs and the ability to hook memory inside the box or across boxes over its OpenCAPI Memory Interface riding atop the Bluelink SerDes. (AMD is offering CPU-GPU coherence across its custom “Trento” Epyc 7003 series processors and its “Aldebaran” Instinct MI250X GPU accelerators in the “Frontier” exascale supercomputer at Oak Ridge National Laboratories.)
We are convinced that the Gen-Z and OpenCAPI technology will help make CXL better, and Boost the kinds and varieties of coherence that are offered. CXL initially offered a kind of asymmetrical coherence, where CPUs can read and write to remote memories in accelerators as if they are local but using the PCI-Express bus instead of a proprietary NUMA interconnect – that is a vast oversimplification – rather than having full cache coherence across the CPUs and accelerators, which has a lot of overhead and which would have an impedance mismatch of its own because PCI-Express was, in days gone by, slower than a NUMA interconnect.
But as we have pointed out before, with PCI-Express doubling its speed every two years or so and latencies holding steady as that bandwidth jumps, we think there is a good chance that CXL will emerge as a kind of universal NUMA interconnect and memory controller, much as IBM has done with OpenCAPI, and Intel has suggested this for both CXL memory and CXL NUMA and Marvell certainly thinks that way about CXL memory as well. And that is why with CXL 3.0, the protocol is offering what is called “enhanced coherency,” which is another way of saying that it is precisely the kind of full coherency between devices that, for example, Nvidia offers across clusters of GPUs on an NVSwitch network or IBM offered between Power9 CPUs and Nvidia Volta GPUs. The kind of full coherency that Intel did not want to do in the beginning. What this means is that devices supporting the CXL.memory sub-protocol can access each other’s memory directly, not asymmetrically, across a CXL switch or a direct point-to-point network.
There is no reason why CXL cannot be the foundation of a memory area network as IBM has created with its “memory inception” implementation of OpenCAPI memory on the Power10 chip, either. As Intel and Marvell have shown in their conceptual presentations, the palette of chippery and interconnects is wide open with a standard like CXL, and improving it across many vectors is important. The industry let Intel win this one, and we will be better off in the long run because of it. Intel has largely let go of CXL and now all kinds of outside innovation can be brought to bear.
Ditto for the Universal Chiplet Interconnect Express being promoted by Intel as a standard for linking chiplets inside of compute engine sockets. Basically, we will live in a world where PCI-Express running UCI-Express connects chiplets inside of a socket, PCI-Express running CXL connects sockets and chips within a node (which is becoming increasingly ephemeral), and PCI-Express switch fabrics spanning a few racks or maybe even a row someday use CXL to link CPUs, accelerators, memory, and flash all together into disaggregated and composable virtual hardware servers.
For now, what is on the immediate horizon is CXL 3.0 running atop the PCI-Express 6.0 transport, and here is how CXL 3.0 is stacking up against the prior CXL 1.0/1.1 release and the current CXL 2.0 release on top of PCI-Express 5.0 transports:
When the CXL protocol is running in I/O mode – what is called CXL.io – it is essentially just the same as the PCI-Express peripheral protocol for I/O devices. The CXL.cache and CXL.memory protocols add caching and memory addressing atop the PCI-Express transport, and run at about half the latency of the PCI-Express protocol. To put some numbers on this, as we did back in September 2021 when talking to Intel, the CXL protocol specification requires that a snoop response on a snoop command when a cache line is missed has to be under 50 nanoseconds, pin to pin, and for memory reads, pin to pin, latency has to be under 80 nanoseconds. By contrast, a local DDR4 memory access one a CPU socket is around 80 nanoseconds, and a NUMA access to far memory in an adjacent CPU socket is around 135 nanoseconds in a typical X86 server.
With the CXL 3.0 protocol running atop the PCI-Express 6.0 transport, the bandwidth is being doubled on all three types of drivers without any increase in latency. That bandwidth increase, to 256 GB/sec across x16 lanes (including both directions) is thanks to the 256 byte flow control unit, or flit, fixed packet size (which is larger than the 64 byte packet used in the PCI-Express 5.0 transport) and the PAM-4 pulsed amplitude modulation encoding that doubles up the bits per signal on the PCI-Express transport. The PCI-Express protocol uses a combination of cyclic redundancy check (CRC) and three-way forward error correction (FEC) algorithms to protect the data being transported across the wire, which is a better method than was employed with prior PCI-Express protocols and hence why PCI-Express 6.0 and therefore CXL 3.0 will have much better performance for memory devices.
The CXL 3.0 protocol does have a low latency CRC algorithm that breaks the 256 B flits into 128 B half flits and does its CRC check and transmissions on these subflits, which can reduce latencies in transmissions by somewhere between 2 nanosecond and 5 nanoseconds.
The neat new thing coming with CXL 3.0 is memory sharing, and this is distinct from the memory pooling that was available with CXL 2.0. Here is what memory pooling looks like:
With memory pooling, you put a glorified PCI-Express switch that speaks CXL between hosts with CPUs and enclosures with accelerators with their own memories or just blocks of raw memory – with or without a fabric manager – and you allocate the accelerators (and their memory) or the memory capacity to the hosts as needed. As the diagram above shows on the right, you can do a point to point interconnect between all hosts and all accelerators or memory devices without a switch, too, if you want to hard code a PCI-Express topology for them to link on.
With CXL 3.0 memory sharing, memory out on a device can be literally shared simultaneously with multiple hosts at the same time. This chart below shows the combination of device shared memory and coherent copies of shared regions enabled by CXL 3.0:
System and cluster designers will be able to mix and match memory pooling and memory sharing techniques with CXL 3.0. CXL 3.0 will allow for multiple layers of switches, too, which was not possible with CXL 2.0, and therefore you can imagine PCI-Express networks with various topologies and layers being able to lash together all kinds of devices and memories into switch fabrics. Spine/leaf networks common among hyperscalers and cloud builders are possible, including devices that just share their cache, devices that just share their memory, and devices that share their cache and memory. (That is Type 1, Type 3, and Type 2 in the CXL device nomenclature.)
The CXL fabric is what will be truly useful and what is enabled in the 3.0 specification. With a fabric, a you get a software-defined, dynamic network of CXL-enabled devices instead of a static network set up with a specific topology linking specific CXL devices. Here is a simple example of a non-tree topology implemented in a fabric that was not possible with CXL 2.0:
And here is the neat bit. The CXL 3.0 fabric can stretch to 4,096 CXL devices. Now, ask yourself this: How many of the big iron NUMA systems and HPC or AI supercomputers in the world have more than 4,096 devices? Not as many as you think. And so, as we have been saying for years now, for a certain class of clustered systems, whether the nodes are loosely or tightly coupled at their memories, a PCI-Express fabric running CXL is just about all they are going to need for networking. Ethernet or InfiniBand will just be used to talk to the outside world. We would expect to see flash devices front-ended by DRAM as a fast cache as the hardware under storage clusters, too. (Optane 3D XPoint persistent memory is no longer an option. But there is always hope for some form of PCM memory or another form of ReRAM. Don’t hold your breath, though.)
As we sit here mulling all of this over, we can’t help thinking about how memory sharing might simplify the programming of HPC and AI applications, especially if there is enough compute in the shared memory to do some collective operations on data as it is processed. There are all kinds of interesting possibilities. . . .
Anyway, making CXL fabrics is going to be interesting, and it will be the heart of many system architectures. The trick will be sharing the memory to drive down the effective cost of DRAM – research by Microsoft Azure showed that on its cloud, memory capacity utilization was only an average of about 40 percent, and half of the VMs running never touched more than half of the memory allocated to their hypervisors from the underlying hardware – to pay for the flexibility that comes through CXL switching and composability for devices with memory and devices as memory.
What we want, and what we have always wanted, was a memory-centric systems architecture that allows all kinds of compute engines to share data in memory as it is being manipulated and to move that data as little as possible. This is the road to higher energy efficiency in systems, at least in theory. Within a few years, we will get to test this all out in practice, and it is legitimately exciting. All we need now is PCI-Express 7.0 two years earlier and we can have some real fun.
The best editor is the person who can take a modest story and make it big, broad, and powerful. Image: Shutterstock
We can only wonder what Mark Twain would have said about ‘editorial responsibility for a brand,’ but irrespective, he would have to concede it’s an idea which has fully arrived. The designations commonly used may not fully cue this, but brands and businesses are publishers and they need editors.
Brands as stories
When marketing storytelling is done well, it establishes what your brand is all about—its purpose, core values, and mission. It offers the consumer more than just a product or service, but rather an idea and a connection. Marketing has remained the same, but the tools and approaches have transformed. Building an editorial mindset is the first step to inclusive authenticity.A well-defined story strategy proves to be an invaluable tool. Brands built on clearly expressed core values have, in a sense, declared the truth they plan to live. The process involves inviting the agents of authenticity to be your allies. Open your doors and let them say to your face what they'll be tweeting and blogging about anyway.
Embody each of your core brand values in their purest form. If you have built a story strategy around uniqueness—the expression of personal gifts, creativity, and nonconformity—you may identify someone who is unwavering in commitment to uniqueness and is extremely articulate about belief in that value.
We can no longer treat our audiences as passive consumers of marketing messages. They must be our partners. And we cannot create those partnerships by simply intruding into their lives and manipulating their actions. Superficially dressing up old tactics in terms of engagement rarely delivers any result from a bored audience.
People who believe and tell the same stories hold the same values. This is what constitutes a worldview. This is what builds a society. In fact, a social norm is just a collection of stories about the who, what, and why of things as they are. Therefore, stories serve as fundamental ingredients in allowing people to create a shared sense of being. Shared stories lead to shared values, which lead to a shared worldview. This calls for attention to the goings on in the world as an Editor would provide it.
The editorial craft
But before we get to brand managers as Editors let us first note what the great Editors do. What is the essence of their craft?Editors create fine stories. They have judgement, instinct, and assertion. Like film is a director’s medium, a good editor sees a larger picture, its scope and impact. The best editor is the person who can take a modest story and make it big, broad, and powerful. Most of us, for a variety of reasons, take big stories and shrink them. A great brand editor will be like a great river in the plains, not a rushing mountain stream.Also read: Simply Speaking: Brand charisma is experienced but not understood
Brand stories activate emotions and communicate values. Your brand story is a complete picture of various elements from website copy to social media to traditional ads. It is the way your brand presents itself to the world and the way the public perceives you. Even when you don’t communicate, you actually do.
We need narratives to inspire others to join our cause, for our sales team to convince people to buy, and for our customer support centres to convey a positive experience.
Brand narratives evolve, changing to suit the product, the market, culture, and the audience. A brand’s story must be true, and it must help sell whatever it is you’re selling. You can’t control a brand’s narrative and your audience may take it places you’d never expect it to go, but you can shape it.
The most important rule of brand storytelling and the one most difficult to put into editorial gear is that Your brand is not the hero, the consumer is. To resonate with your audience, content should put the consumer first.
Editors who run brands as fountains of content must set their ambitions to create compelling narratives. When done successfully, a great brand story should create change. If not a huge change, at least an improvement of some kind. Also read: Should brands dissociate with influencers who promote toxic content?
The editor must run the content engine such that it can routinely land an emotional impact or advantage. The story involves the people you are selling to, so drop the spin and tell the truth. The best brand stories are real. But we live in a mutation era where even the internet is going from 2D to 3D, and with the imminent full bloom of the Metaverse, even more people will engage brands beyond reality.
Nearly a hundred million people a day log on to Roblox, Minecraft, and Fortnite Creative, platforms that operate tens of millions of interconnected worlds, which support a consistent virtual identity, virtual goods, and communications suites, and can be accessed from most devices. Most time on these platforms is spent on leisure-playing games and attending concerts—but we are starting to see people go further. No brand or business can neglect its representation given such a massive shift to new media.
The editorial role beyond advertising
Many will argue that such editorship has always been a part of great brand building. Indeed, that is true. But the scale, scope and implications have transformed. In the earlier era, advertising was the exclusive language of a brand.Steve Jobs famously said, “it’s better to be a pirate than to join the navy” and that attitude drove a lot of Apple’s most significant product launch campaigns. 1984, an iconic ad, created by TBWA\Chiat\Day and directed by Ridley Scott put Apple on the map at the Super Bowl.
Based on George Orwell’s dystopian novel, the ad cost $650,000 to make and featured a British discus thrower as the woman who stops crowds of men from mindlessly following the words of a dictator on the screen. The ad made a deep statement, on American politics as well as its rivals IBM, in the middle of a very challenging political climate. It proclaimed that ‘Apple was revolutionary.’Also read: Storytelling: Not just a good old practice
But it almost did not air. Test groups found it to be one of the least effective commercials made. Steve Jobs—one of the greats if ever Brand Editors had a hall of Fame—saw to it.
Taking a risk is the hallmark of a great Editor as is a spine of tempered steel.
It was only in 1997 that Think Different was launched, but this advert seeded the spirit much ahead in time.
Not only brands but also the business entity can tell a story—at each stage of its evolution. It has a huge bearing on how it evolves and has value. Ever wondered how a company that has never turned a profit has a multibillion-dollar valuation? Why do some startups attract large investments while others do not? The power of the story very substantially drives corporate value. In business, some storytellers spin compelling narratives essential to success. Tesla, RedBull, Nike, Disney, Apple, and Amazon are all examples of how a company's editorial track can enrich and constrain its narrative.
There are brilliant examples of brand editing everywhere. Some of the most exciting content initiatives are going beyond blogs and articles, to podcasts, video series, and even experiential, real-life encounters. Brand editors take authentic content and find new platforms and avenues on which it can continue to expand ideally in ways that are profitable for their brand.
Editorial stance
A key part of the editorial discipline is to decode the brand DNA in terms of voice, tone, style, and rhythm. Deciding who you are not, is a lot more difficult than deciding who you are. That’s also the essence of strategy. This editorial stance matters to consumers at a conscious and subliminal level. Like you choose a newspaper aligning to its editorial outlook and treatment of issues, likewise, consumers respond to brand narratives whilst making choices. Also read: Ten ways to establish your personal brandIf the brand is a developing story, it can have many editors, each responsible for a different aspect. Put together, the editors create the community glue for the brands’ audiences—arguably the most significant and influential element of modern marketing.A difficult road
Brand editors will not find the road smooth. They will be pushed around wrt their roles and remits. Many well-minded stakeholders may still think there is an encroachment on their turf. Many will resist arguing it's much ado about nothing.Keep in mind that you’re a communicator you have to create the conviction internally as much, if not more, than with consumers. The realisation needs to grow that everyone communicates even if that’s not their job.
Everything you write has a purpose, and your audience must understand your content before they can act on it. In other words, clarity leads to engagement. Engagement leads to conversations. Conversation, when done right, ends in conversions. Whenever you write a product description, a social media post, or a story for your website, you’re using the power of your words to inspire your readers to act. And whenever you write, you are obliged to edit. Good editing will embrace your identity and help you craft memorable, effective content to keep you top of mind for your audience. Also read: How to fix the brand crisis of consumer internet companies
As I conclude, let me again emphasise that Consumer is Queen—audiences are savvy enough now to know the difference between editorial writing and sales writing, and it’s editorial they prefer. Brands not only need to find people who excel at creating content rather than selling it but let them have the freedom necessary to create this kind of quality editorial.
A few years ago, Seth Godin said that content marketing is the only marketing left. Why would Gillette not run the most important online magazine for men? Why didn’t Encyclopaedia Britannia start a search engine to organise the world’s information? They could have been Google if they took a bigger view of their role as a brand and institution.
I think part of the challenge is that we must redefine what business we’re in and shift to a different way of thinking and empower some really smart people with the resources and creative freedom to go out and make great content. It’s about mattering.
The rise of brand journalism signals an exciting time in media, and it shows no signs of slowing down. More and more brands are growing their editorial teams and branching into new forms of quality content.
Happy Editing.
“You can say the right thing about a product and nobody will listen. You’ve got to say it in such a way that people will feel it in their gut. Because if they don’t feel it, nothing will happen.” - William Bernbach
References:
The Power of Myth – Campbell and Moyers
Inside Apple – Adam Lashinsky
Winning The Story Wars – Jonah Sachs
The Mirror Makers: A History of American Advertising and its Creators – Stephen R Fox
Shubhranshu Singh is vice president, marketing - domestic & IB, CVBU, Tata Motors. He writes Simply Speaking, a weekly column on Storyboard18. Views expressed are personal.
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Staffordshire Police
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London, England
£400.00 - £450.00 per day
Hays
Learning & Performance BP, 400 a day, 6 months, Tech Firm, London, Partially Remote
Homeworking
GBP70000 - GBP95000 per annum + Benefits inc. Bonus
Bramwith Consulting
Procurement Managing Consultant / Best-in-Class Consultancy / Home Based Contract / Birmingham / £70,000 - £95,000 + Benefits inc. Bonus
London
£65000.00 - £75000.00 per annum + plus bonus and benefits
DNA Recruit
Account Director - Brand Partnerships and Activation Agency - London - £75K
Riyadh
GBP50000 - GBP60000 per annum +
Bramwith Consulting
Global Procurement Consultancy seeking a Procurement Officer specialising in Directs and Raw Materials - Joining a world renowned construction project
City of London, England
£60000.00 - £90000.00 per annum
Hays
Senior Talent Acquisitions Partner within Technology in a Leading Fortune 500 Tech Solutions Firm
London, City of London
Negotiable
DNA Recruit
Are you are Strategist with passion for shopper and retail?Would you like to be part of an inspiring team and work with some of the best brands in the
London
£70000 - £80000 per annum
Major Players
Creative Director We are working with a alternative, independent creative agency who are looking for a Creative and art direction lead for global spor
London (Central), London (Greater)
circa £75k
Corporate Communications Recruitment
Leading Communications agency are looking to hire a Sustainability communications lead/director. London based vacancy!
Macclesfield, Cheshire
Up to £75,000 + package
Langley Search & Interim
Is finding strategic value in Marketing & Martech spend a passion of yours? Then bring your experience with you to a leading Financial Firm! My Cli...
London (Central), London (Greater)
circa £100k
Corporate Communications Recruitment
Our client is an international specialist comms. consultancy. They are looking to hire a Media Coach with a financial journalism background.
London (Central), London (Greater)
circa £100k
Corporate Communications Recruitment
Our client is a Consulting and Communications agency. They are looking to hire an IR Consultant with experience of capital markets and investor days.
London (Central), London (Greater)
up to £100k
Corporate Communications Recruitment
An award winning global integrated agency with a strong corporate branding offer are looking to hire a head of brand strategy. Great opportunity!
London, England
£50000.00 - £56000.00 per annum
Hays
Resource Manager, International Consulting Firm, 50K - 55K, London, Permanent, Hybrid.
Flexible (Role based from one of this charity's 4 National offices, remote/hybrid working available)
£47,692 - £53,111 per annum plus excellent benefits
CHM
Could you lead a team of project, production and technical managers, and oversee the management of all this charity's Digital Projects & Programmes?
London
£50,000 - £60,000 Per Annum
NFP People
We are looking for an exceptional Public Realm Manager with drive, and ambition to contribute to making the area more sustainable and welcoming.
Dover – hybrid working (3x days in office)
Circa £100,000
VMA Group
Fantastic opportunity for a Head of Communications to join a well known business in the transportation and logistics sector.
Leeds
£60,000 - £65,000
Michael Page Client Branded
Head of Supply Chain for BookTrust, the UK's largest children's practicing charity Exciting period of transformation as part of their 5 year strate...
London
£60000.00 - £70000.00 per annum + bonus & benefits
DNA Recruit
PR & Communications Director to join independent digital agency salary: £70K get in touch
Homeworking
GBP90000 - GBP95000 per annum + Package
Bramwith Consulting
Role: IT/BPO Procurement Outsourcing Consultant Firm: FTSE 250 Professional Services Firm Salary: £90,000 - £95,000 + Package Location: London Contact
London
GBP50000.00 - GBP70000.00 per annum + Excellent Bonus, Rapid Progression
Bramwith Consulting
Senior Procurement Consultant - MULTIPLE POSITIONS - Specialist Procurement Consultancy - London + Flexible Working - £50,000 + £70,000 + BONUS
London
GBP55000 - GBP65000 per annum + Package, Rapid Progression
Bramwith Consulting
Direct Procurement Senior Consultant - Leading Boutique Procurement Consultancy - London / South-East - £55,000- £65,000 Leading Boutique Procurement Consultancy is looking for a direct procurement senior consultant to bolster their rapidly growing
Oxfordshire, England
£50000.00 - £55000.00 per annum
Hays
Talent Acquisition Manager - Central Oxford - Hybrid - Up to £55,000
New York
£70000 - £85000 per annum
Major Players
Copywriter A leading global company is looking for an experienced Copywriter to join their team in New York working in the Marketing Consumer departme
London (Central), London (Greater)
95000 - 110000
f1 Recruitment
A long-standing, forward thinking client of ours is looking for a Director / Board Director ideally with Financial Services experience or from anot...
London (Central), London (Greater)
to £70k + good bonuses/benefits
Fill Recruitment
Experience design consultancy seeks an Account Director or Senior Account Director for London / Bristol or remote working
London
GBP60000 - GBP65000 per annum + Bonus
Bramwith Consulting
Role: IT Procurement Manager- World Renowned Fashion Retailer - London - £65K + Bonus + Benefits Global Leading Fashion Retailer presents a uniquely exciting opportunity for an ambitious IT Procurement Manager to autonomously manage a spend of £200m
Homeworking
GBP45000 - GBP65000 per annum + Bonus
Bramwith Consulting
Indirect Marketing Procurement Manager / FMCG / Globally Loved Brand / London / £45,000 - £65,000 + Benefits inc. Bonus
London, England
£75000.00 - £80000.00 per annum
Hays
Senior HR Business Partner 12 Month FTC London City 2 days in the office £75,000 - £80,000
City of London, England
£55000 - £60000 per annum
Morgan Law
My client is looking for a Head of HR to join their unique not for profit organisation on a 12 month contract. Based in the West End this small but prestigious charity offers the opportunity to work at strategic level reporting into the CEO.
London, City of London
Up to £350 per day
Major Players
Freelance Digital Marketing Manager - 6-month contract - Flexible Hybrid - £350 per day [Inside IR35] Major Players are working with an industry leadi
New York
Negotiable
Major Players
This pioneering blockchain engineering company created a well known and succesful crypto currency. They are also currently working on a number of exci
London (Central), London (Greater)
To £80k plus benefits
Agencyland Limited
Are you an experienced Account Director who feels ready for their first Business Director role?
Homeworking
GBP65000 - GBP75000 per annum + + Benefits
Bramwith Consulting
This household name is seeking a bright & commercially aware indirect procurement candidate to join their growing function.
London
GBP60000 - GBP65000 per annum + + Package
Bramwith Consulting
This expansive and global organisation are currently undergoing an exciting transformative period internally, and are now seeking a Procurement Business Partner specialising within commercial entertainment and production to join their highly specialised p
London
GBP60000 - GBP65000 per annum + + Package
Bramwith Consulting
This expansive and global organisation are currently undergoing an exciting transformative period internally, and are now seeking a Procurement Business Partner specialising within commercial entertainment and production to join their highly specialised p
CHILTERNS MS CENTRE, Near Wendover, Aylesbury, HP22 5LX
Hours approx. 30 to 37.5 hours per week. FTE Salary £60,000 to £65,000
Chilterns MS Centre Ltd
This is an exciting time for a dynamic CEO to lead the Chilterns MS Centre into its next chapter - a period of growth and expansion into new services.
London
£350 - £370 per day
mustard md
Are you a Freelance Designer/ Artworker skilled in PPT & Keynote? I have the pleasure of working with one of the globes leading entertainment brands...
London
£300 - £350 per day
mustard md
Freelance Motion Graphic Designer with availability from Mid August? I have the pleasure of working one the globes leading entertainment brands who are looking for...
Nationwide
£60,000
Music for Youth
We are seeking an exceptional Development Director with excellent knowledge of fundraising and philanthropy to lead and develop Music for Youth’s f...
Blended between office and home (England and Wales)
£45,822 (Including £2610 market premia)+ £3520 London Allowance if applicable
Citizens Advice
Do you want to work for an organisation that makes a difference, every single day, to people from all walks of life?
Homeworking
GBP55000 - GBP65000 per annum + + Car & Benefits
Bramwith Consulting
Iconic FMCG brand seeks a high-achieving procurement expert to join the ranks and drive a crucial spend category towards best-in-class.
London, England
£70000.00 - £90000.00 per annum + Bonus, hybrid, negotiable
Hays
Reporting to the Director, Global Compensation, the Global Investments Compensation Manager will be responsible for providing advisory services to senior business leaders and HR business partners within our investment teams, in alignment with OMERS compen
London, England
£50000 - £60000 per annum
Hays
HR Advisor/Junior HRBP, 55K, 16 Month FTC, Investment Management Firm, Flexible Hybrid Working, London
Homeworking
GBP75000 - GBP80000 per annum + Benefits
Bramwith Consulting
Iconic brand seeks a high-achieving procurement expert to join the ranks and drive a crucial spend category towards best-in-class.
City of London
GBP65000 - GBP75000 per annum + + Package + Flexi Working
Bramwith Consulting
Indirect Senior Procurement Manager - Global Pharmaceutical - North West London - 65-75K + package + flexible working
London
GBP35000 - GBP70000 per annum + Bonus
Bramwith Consulting
Indirect Procurement Consultant / Multiple Levels / Management Consultancy / Rapid Career Progression / London / Flexible Working / £35,000 - £70,000 + Benefits inc. Bonus
London
£75000 - £80000 per annum
Major Players
ROLE: Associate Creative Director (Copywriter) Rare opportunity to work with an international integrated communications agency! Key Responsibilities
Chelmsford
GBP75000 - GBP80000 per annum + + Benefits
Bramwith Consulting
Rapidly growing professional services firm seeks an experienced indirect procurement leader to join their procurement function during a period of exciting transformation and growth.
South West England
to c£60k + bens and flexible working
Langley Search & Interim
My client, a logistics and supply chain transformation specialist, are looking to recruit a Subcontract Manager to work within a team managing high...
London (Central), London (Greater)
Salary DOE plus bonus
createselect
Global Business Director ideally with drinks experience needed for a stunning agency in the emerging tech space.
London
£56k per year
Harris Hill
Working for a health membership organisation, to best promote, market and communicate the continual professional development benefits of membership.
London (Central)
up to c.£85k + bonus and benefits
Premier Resourcing UK
Brand new in-house Group Internal Communications and Change Management Lead position with global organisation.
Leicester, Leicestershire
Competitive salary plus benefits
PA Housing
We’re looking for a proven HR & OD leader, who can draw on accomplished people and programme management skills to bring about organisational change.
Andover, England
£50000.00 - £60000.00 per annum
Hays
A Senior HRBP role in Andover paying up to £60,000 pa doe for a multinational consumer goods organisation.
London
£50k per year
Harris Hill
Make your mark in a dynamic business-facing non-profit organisation, working to get messages across to key audiences and Capital Markets stakeholders
Homeworking
GBP70000 - GBP75000 per annum + Benefits
Bramwith Consulting
This innovative flexible real estate services firm is searching for a strong Sourcing Manager to join their young, growing procurement team.
Royal Docks, E16
£81,537 per annum
Greater London Authority
This is a really exciting opportunity for a highly skilled comms professional to play a leading role in shaping the work of the London Assembly. Th...
Homeworking
GBP75000 - GBP90000 per annum + Bonus
Bramwith Consulting
Indirect Procurement Managing Consultant / Best-in-Class Boutique Management Consultancy / London / Flexible Working / £75,000 - £90,000 + Benefits inc. Bonus
Soho
£80/95K
Barker Graves
This is a first-class opportunity to work at one of London'sbest integrated creative agencies for an experienced Senior Account Director looking to...
Newark
USD90000.00 - USD110000 per annum + Bonus + Private Health
Bramwith Consulting
Global Procurement Manager - HR & Professional Services Fortune 100 FMCG Newark, New Jersey $110,000 + Bonus + Private Healthcare Global FMCG seeks an ambitious procurement specialist to join their team in a newly created role to support the d
Boston
USD130000.00 - USD140000.00 per annum + Excellent Bonus
Bramwith Consulting
Senior Procurement Manager - GNFR - Global Retailer - Boston, MA - $130,000 - $140,000 + Package This global fashion retailer is looking to build out their Greenfield Procurement function across the North America region and is seeking an experienc
City of London, England
£65000.00 - £70000.00 per annum
Hays
Learning and Development Manager, Permanent, Oxfordshire / Berkshire
London, City of London
£50 - £70 per hour
Major Players
Freelance Paid Search / PPC Specialist - Hybrid - £50 - £70 per hour Major Players are working with a well-known beauty subscription brand, selling hi
Kings Norton, Birmingham
£90,000 - £100,000 per annum
Harris Hill
We are a charity working across the West Midlands to provide quality services for autistic people and their families. We are looking for a strategi...
City of London, London
£300 - £350 per day
Major Players
Freelance Display Planning Manager - Flexible Hybrid - £350 per day [Outside IR35] Major Players are working with a globally recognised agency, workin
London
GBP55800 - GBP69000 per annum (dependent on experience)
Notting Hill Genesis
Summary Can you help us to deliver outstanding residential-led developments through successful partnerships with our contractors and professional con
Oxford, England
Up to £80000.00 per annum
Hays
A great new role to support the global HR transformation within a charity.
Betsi, North Wales
Pay Band 9
Betsi Cadwaladr University Health Board
This is a new role for us at Betsi, and we are seeking an exceptional people leader with passion, energy and insight, and the experience to support...
London
GBP40000 - GBP70000 per annum + + Package
Bramwith Consulting
An exciting opportunity has arisen to join a leading, niche, UK Management Consultancy; this organisation are seeking a results orientated, innovative procurement specialist to join their expansive function.
London (Central)
Depending on experience
Premier Resourcing UK
Director of International PR GV5400 An integrated marketing communications consultancy have a fantastic opportunity to join a senior role as Di...
Lincolnshire
Negotiable
Major Players
Marketing Operations Manager - New York - Working with Sports, Fashion, Events and Media!Major Players are working with a global market leader in spor
London
Negotiable
Major Players
Design Director - New York - Working with Sports, Fashion, Events and Media!Major Players are working with a global market leader in sports, fashion,
St. Albans, England
£95000.00 - £110000.00 per annum
Hays
Permanent Head of HR / HR Director, Near to ST Albans, £95,000-£110,000 + Benefits
London
£45.5k - 53k per year
Harris Hill
Harris Hill are working with one of the UK's leading charities who is looking for a new Head of New Product Development and Innovation
London, England
Up to £70000.00 per annum
Hays
HR Business Partner London - Hyrbid £70000pa
Brighton, England
£50000.00 - £60000.00 per annum + benefits
Hays
Head of Employee Policy and Relations for the University of Sussex in Brighton
Homeworking
GBP70000 - GBP85000 per annum + Package
Bramwith Consulting
Role: Software Sourcing Manger Firm: UK Leading Banking Group Location: London - Hybrid Working Salary: £70,000 - £85,000 + Package Contact: Tabitha -
City of London
GBP80000 - GBP90000 per annum + bonus + flexi working
Bramwith Consulting
Head of Procurement Strategy - First-Class Procurement Function - £80-90k + Bonus + Package Location: Nationwide offices, including Manchester, Birmingham, and London (home working available)
Leeds
£60,000 - £65,000
BookTrust
Head of Supply Chain for BookTrust, the UK's largest children's practicing charity Exciting period of transformation as part of their 5 year strate...
Outside London
Competitive base + full benefit's package
PA Consulting
Commercial & Procurement Specialist We adopt a hybrid model at PA, but your office base will be in the location nearest to you: Bristol, Cheltenha...
Warwick
£50,000 - £55,000 Per Annum
NFP People
This organisation is seeking a talented, enthusiastic Head of Evaluation, Insights and Learning to join at this stage of the charity’s development.
Stratford, London
£54,873 – £60,366
East London Waste Authority (ELWA)
Procurement Programme Manager East London Waste Authority (ELWA) £54,873 – £60,366 Full time Location: Stratford, London About the role We have a...
Cambridge, Cambridgeshire
Circa £60 - £65k pa pro rata (pay review pending)
Arthur Rank Hospice Charity
The role provides strategic leadership & financial strategy for the Charity & is accountable for the provision of financial & performance information.
Homeworking
GBP60000 - GBP70000 per annum + + Benefits
Bramwith Consulting
Highly regarded Technology organisation seeks an experience technology procurement candidate to join a newly created role in their expanding procurement function.
London, England
£70000.00 - £90000.00 per annum + Bonus, hybrid, negotiable
Hays
Reporting to the Director, Global Compensation, the Global Investments Compensation Lead will be responsible for providing advisory services to senior business leaders and HR business partners within our investment teams, in alignment with OMERS compensat
London, England
Up to £65000.00 per annum + + bonus + benefits
Hays
Senior HR Business Partner London - Hybrid £65000 + Bonus + Benefits
London / flexible base, with regular meetings in London
£74k London / £70k regional
NCVO
This new role will see you work to deliver and embed the cultural change that provides the foundation for delivering our organisational strategy.
Loughborough / Hybrid Working
£45,000 - £50,000 per annum
Youth Sport Trust
We are looking for an inspirational and experienced Head of Policy & Public Affairs to join our senior leadership team.
London (Central), London (Greater)
to £80k + great benefits
Fill Recruitment
Ambitious central London customer engagement agency seeks a Business Director / equivalent with strong CRM experience
London (Central)
Depending on experience
Premier Resourcing UK
Associate Director / Senior Associate Director – Energy & Sustainability GV5409 Exciting London agency looking to recruit someone with publ...
London, England
£65000.00 - £90000.00 per annum + Bonus, hybrid, negotiable
Hays
Reporting to the Associate Director, Payroll and Global Mobility, the incumbent will lead the day-to-day activities of global mobility programs.
Peterborough, England
£55000.00 - £70000.00 per annum + car or car allowance, PMI
Hays
Strategic HR Business Partner for global organisation in Peterborough, up to £70k + car allowance, PMI, hybrid
Reading
GBP60000 - GBP65000 per annum + bonus + flexi working
Bramwith Consulting
IT Procurement Manager - FTSE 250 Global FMCG Location: practicing (Hybrid options available) Salary: £60,000 - 65,000 + excellent package
Homeworking
GBP50000 - GBP60000 per annum + + Package + Flexi Working
Bramwith Consulting
Packaging Strategic Procurement Manager - Global and Iconic FMCG brand Location: London/Remote Salary: £50-60k + package
London
£80000 - £100000 per annum + work from home, unlimited holiday
Stonor
Finance Director role for growing marketing agency...
Gloucestershire, England
£65000 - £75000 per annum
Morgan Law
Morgan Law are delighted to be recruiting for our public sector client based in Gloucestershire who are currently looking for an experienced Interim Associate Director of Resourcing.
London (Greater)
£57,471 - £67,902
BFI
Salary £57,471 - £67,902 per annum We support flexible working We are seeking a Head of Procurement to be responsible for the provision of professi...
St. Helens, England
Up to £65000.00 per annum
Hays
Permanent - National HR Manager - Full time - Hybrid Model - Exciting opportunity
London, England
£65000.00 - £70000.00 per annum
Hays
Interim Regional HR BP- 12 month FTC - Facilities Management - London - c£65,000 - £70,000 plus car allowance
London
Up to £350 per day
The Great & The Good
*Freelance Account Director* Advertising agency, London | 9m contract | TVC & ATL campaigns
London
£60000 - £70000 per annum
Major Players
Creative Lead, Augmented RealityLondon (Hybrid/must be UK based)Perm or freelance to permOur leading tech co specialising in Augmented Reality (AR) is
Temporarily Remote
£63,062 - £67,417 per annum (Plus £3,300 London Weighting if applicable)
NEA
National Energy Action is looking for a Director of Homes who will lead the charity's work to Boost the lives of people in fuel poverty.
London, England
£100000.00 - £120000.00 per annum
Hays
Head of Executive & Partnering Talent Acquisition and Candidate Experience
London (Greater)
£80,000 - £90,000
VMA Group
As Head of Corporate Communications for this FTSE 100 Energy business, you will be working closely with the Group Director of Corporate Affairs, CE...
London
£50,681 - £55,961 per annum
Imperial Health Charity
Deputy Head of Volunteering London, W2 About Us We’re Imperial Health Charity, an organisation that helps our hospitals do more through grants, art...
City of London, England
£75000.00 - £93000.00 per annum
Hays
Senior HR Business Partner / Financial Services / London City
Watford
GBP400 - GBP500 per day +
Bramwith Consulting
This global FMCG company are seeking an interim procurement professional with experience across indirect procurement and ideally an SME in marketing procurement.
London, England
£61000 - £70000 per annum
Morgan Law
My London based NHS client is looking for an experienced Interim HR Business Partner (Band 8b) to join their established team for a period of 6 months.
London, England
£54000 - £60000 per annum
Morgan Law
My London based NHS client is looking for an experienced Interim HR Business Partner (band 8a) to join their establish team for a period of 6 months.
London (Central), London (Greater)
£70k Basic + £30k OTE plus benefits
MODA Consult
This is such an exciting role, a Partnership Director working with tech platforms, at a leading digital / commerce agency. Something really different!
London (Central), London (Greater)
£70k - £75k + benefits / flexible working
MODA Consult
This beautiful brand is looking for an Art Director / Creative to work within their in-house team. Outstanding interior design / furniture brand.
City of London, England
£46727 - £54874 per annum + LGPS Pension Scheme
Morgan Law
Morgan Law are proud to be working with a popular London Based University in their search for an HR Business Partner. Reporting into the Head of Business Partnering you will work with your client group to support them across strategic and operational HR.
London (Central), London (Greater)
£60,000 to £65,000 p.a. depending on experience
Paul Mellon Centre
The PMC seeks an experienced Finance Manager who will be responsible for managing our day-to-day financial processing, systems and reporting.
Homeworking
GBP45000 - GBP60000 per annum + Package
Bramwith Consulting
Role: Indirect Procurement Category Manager Firm: FTSE100 Professional Services Firm Location: London / Remote Salary: £50,000 - £60,000 + Package Th
City of London, England
Negotiable
Hays
Interim Talent Acquisition Specialist - Global Engineering - Rolling Contract
London
£70000 - £80000 per annum
The Great & The Good
Amazing opportunity for a CX Group Account Director to join a fast-growing London agency.
Homeworking
GBP70000 - GBP90000 per annum + Package
Bramwith Consulting
Role: Procurement Software Sourcing Lead Firm: Global Professional Services / BPO Location: London / 90% Remote Salary: £70,000 - £85,000 + Package T
London, England
£50000.00 - £60000.00 per annum
Hays
TA Partner, 50K-60K, 5K travel allowance plus 15% bonus, hybrid model.
London, England
£60000.00 - £65000.00 per annum
Hays
Senior TA Partner, 60K - 65K, London, Permanent, Hybrid Working, American Real Estate and Investment Firm.
Berkshire
GBP75000 - GBP80000 per annum + car + bonus
Bramwith Consulting
Global Commodity Price Risk Manager (CPRM) - Global and Iconic FMCG brand Location: London/Remote Salary: £75-80k + car + package
London, England
£60000.00 - £65000.00 per annum
Hays
Fully Remote Senior Recruiter EMEA, Data Centre/Tech Firm, 60K-65K, Permanent.
Hertfordshire
£90,000 - £95,000 p.a.
Harris Hill
Harris Hill is delighted to be working with a hospice based in Letchworth Garden City to recruit a new Chief Executive. The hospice exists to provi...
Homeworking
GBP50000 - GBP60000 per annum + + Package + Flexi Working
Bramwith Consulting
Directs Strategic Procurement Manager - Global and Iconic FMCG brand Location: London/Remote Salary: £50-60k + package
London, England
Negotiable
Hays
Interim HR Talent Implementation Project Manager - London Hybrid - Immediate start - Inside scope. Manage design and implementation of the Talent Management related modules on Success Factors.
London, England
£90000.00 - £110000.00 per annum
Hays
Head of HR operations, Flexible on Location, Hybrid, Permanent
Lincoln, Lincolnshire
Up to £63,862 per annum + benefits
Castlefield Recruitment
United Lincolnshire Hospitals NHS Trust (ULHT) are looking to identify a Head of Category – Clinical to join our Procurement Department. The role s...
London (Central), London (Greater)
Competitive day rates
Fill Recruitment
Freelance SAMs, Account Directors, SADs, Group Account Directors and Business Directors required!
London (Central), London (Greater)
to £90k + good benefits
Fill Recruitment
Creative charity / fundraising agency seeks an experienced team leader to join them as their new Client Services Director
Watford
GBP400 - GBP500 per day +
Bramwith Consulting
This global FMCG company are seeking a passionate, up and coming procurement professional to join their renowned procurement function to join their wider Marketing Procurement Team.
Homeworking
GBP70000 - GBP90000 per annum + Package
Bramwith Consulting
Technology Sourcing Manager - UK&I Financial Services Firm - £70-90,000 - Board-Level Exposure - Excellent Progression Opportunities Due to the rapid
Homeworking
GBP70000 - GBP75000 per annum + Package
Bramwith Consulting
Role: Category Manager - Facilities Firm: UK Leading Real Estate Firm Location: London - Hybrid Working Salary: £70,000 - £75,000 + Package A unique
London, England
£47000 - £52000 per annum
Morgan Law
My client, a large NHS Trust based in London are looking for 2 x Band 7 ER Caseworkers/Investigators for an initial 6 months period. The client will also consider secondment or permanent as an option for the right candidate.
London, England
£375.00 - £400.00 per day
Hays
Interim Resourcing Advisor - remote - 6 months
London, England
£500.00 - £592.00 per day
Hays
Interim Compensation Analyst - Immediate start - London Hybrid up to £592 per day Interim Compensation Analyst job Interim Reward Analyst job
London, England
£52000 - £58000 per annum
Morgan Law
My public sector client is looking for an experienced Senior L&OD Manager
South West London, England
Up to £85000.00 per annum
Morgan Law
Ready for the next step in your HR career? We have a great opportunity for an HR Director to join the Executive Team at a private hospital in South London.
Northampton, England
£50000.00 - £60000.00 per annum
Hays
Permanent HR Manager, Northampton-Hybrid-£50,000-£60,000 + £7,000 car allowance.
London, England
£500.00 - £650.00 per day
Hays
Global Talent Acquisition Consultant - Technology brand - 6-9 months
Home based with flexible working
£50,000 - £60,000 Per Annum
NFP People
We are looking for a Business Development and Partnerships Manager who is ambitious and invested in conflict transformation.
London
60,000-65,000
Guy's and St Thomas' Foundation
Be part of a game changing health foundation An instrumental new role in the organisation About Our Client Guy's & St Thomas' Foundation is an i...
Chester, England
£50000.00 - £60000.00 per annum
Hays
Permanent - HR Business Partner - Chester - Full time - Monday - Friday - Competitive Salary - Hybrid Model
London
£55k - 70k per year
Harris Hill
A brilliant opportunity for a senior philanthropy fundraiser.
Remote (UK)
Up to £90k DOE plus benefits
air-recruitment
Are you the senior client services pro this really warm and friendly creative agency need?
London
GBP60000 - GBP70000 per annum + Bonus
Bramwith Consulting
Indirect Procurement Category Lead / Best-in-Class Fashion Organisation / Career Progression / London / £60,000 - £70,000 + Benefits inc. Bonus
London
GBP65000 - GBP80000 per annum +
Bramwith Consulting
Procurement Consulting opportunities - Market Leading Procurement Boutique Consultancy - Private Equity Backed - London + Travel - £65-80k + Package
Flexible Location
£45,000 - £50,000 per annum
One Small Thing
Head of Training and Business Development Flexible Location The Organisation One Small Thing is striving for positive change across the justice sys...
Woking, Surrey, GU21 4LL/Hybrid working
£50,000 - £60,000
WWF
Join the WWF-UK Science team as Chief Advisor for climate issues and play your part in saving our planet.
Milton Keynes, England
£50000.00 - £69000.00 per annum + 27 days holiday & bank holidays
Hays
Senior HR Consultant-Change, 9 Month FTC, £50,000-£69,000, Milton Keynes, Hybrid
Homeworking
GBP50000 - GBP60000 per annum +
Bramwith Consulting
Procurement Category Specialist - Software & Data - Global Leading Law-Firm - London based + home working - £50-60k + packageThis leading global law f
City of London, London
£350 - £450 per day
Major Players
Business Director Performance Content - Hybrid - £450 per day, 6 month contract Major Players are working with a globally recognised agency with unriv
Homeworking
GBP55000 - GBP65000 per annum + + Package + Flexi Working
Bramwith Consulting
IT Procurement Manager - Public Sector - Global Professional Services Firm Salary: £55-65,000 + package Location: Remote (option to base yourself in office)
Reading
GBP60000 - GBP65000 per annum + + bonus + flexi working
Bramwith Consulting
IT Procurement Manager - Global FMCG Location: practicing (hybrid options available) Salary: £60-65,000 + excellent package
Wakefield, West Yorkshire
£58,524 - £63,780 per annum
West Yorkshire Police
People Directorate, Diversity, Equality and Inclusion Department Location: Wakefield Salary: £58,524 - £63,780 per annum 1 permanent post - 37 hour...
Homeworking
GBP80000 - GBP90000 per annum +
Bramwith Consulting
Global Technology Sourcing Manager - Magic-Circle Law Firm - London + flexi-working - £80-90k + package This magic circle law firm, globally renowned
London, England
Up to £60000.00 per annum + + bonus + benefits
Hays
HR Business Partner London - 1 day from office 4 days WFH £60000 + bonus + Benefits
Amsterdam
EUR60000 - EUR80000 per annum + package
Bramwith Consulting
IT Procurement Team Lead - Global FTSE 100 Conglomerate - Amsterdam - €80,000 + Package
Dublin
EUR60000 - EUR80000 per annum + package
Bramwith Consulting
PROCUREMENT - GLOBAL HR/PROFESSIONAL SERVICES CATEGORY MANAGER - ICONIC FTSE 100 PROFESSIONAL SERVICES FIRM - DUBLIN+ FLEX WORKING - €85,000 + COMPREHENSIVE BENEFITS
Dublin
EUR60000 - EUR100000 per annum + strong package
Bramwith Consulting
IT Procurement Lead - Global Fortune 500 Financial Services Firm - Dublin - €60,000 - €100,000 + Package
Dublin
EUR60000 - EUR85000 per annum + strong package
Bramwith Consulting
IT Procurement Lead - Global Fortune 500 Financial Services Firm - Dublin - €60,000 - €85,000 + Package
City of London
GBP40000 - GBP60000 per annum + bonus + benefits
Bramwith Consulting
Strategic Sourcing Manager, IT & Technology - Global FTSE 100 FMCG Player - Home based contract - £40,000 - £60,000 + Bonus & Benefits
Dublin City Centre
EUR60000 - EUR90000 per annum + bonus + benefits
Bramwith Consulting
Strategic Sourcing Manager, IT & Technology - Global FTSE 100 FMCG Player - Dublin- £50,000 - €90,000 + Bonus & Benefits
London (Central), London (Greater), Currently hybrid working
c. £61,000-63,000 pa
Paul Hamlyn Foundation
An exciting opportunity for an exceptional individual to join Paul Hamlyn Foundation as Head of People & Culture.
Woking, Surrey GU21 4LL/Hybrid Working
£64,087 - £80,000
WWF
If you are expert in developing and implementing advocacy strategies this is a unique opportunity to use your skills to save the planet.
London, England
Negotiable
Hays
Interim Benefits Manager EMEA - Financial services - London Hybrid Competitive day rate - inside scope of IR35 Interim Benefits job Interim Benefits Specialist Interim Benefits Consultant
Telford, Old Park (Hybrid)
£54,744 per annum
Networx
Our client has an opportunity for a Governance Services Manager to join their team in Telford.
Islington, London (Greater)
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Revitalise
Head of Capital Appeal City Road, EC1V £59k Permanent / 37.5 hours per week View the full job description and person specification visit our Rev...
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£80,000 pro rata plus benefits
Harris Hill
We are looking for an inspirational and empowering CEO to join us at this exciting and transitional stage of our development. London, £80,000
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£51,000 to £55,000 plus benefits
Young Futures
Our modern, purpose-built, 9-bed therapeutic residential home where young women live in studios is looking for a Residential Team Manager.
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£75,000
Harris Hill
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£75000 - £80000 per annum
Major Players
ROLE: Creative Director (12months FTC) Fabulous opportunity to work with a global e-commerce wellbeing company. Ecommerce experience is a must for thi
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VMA Group
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Chelmsford
GBP75000 - GBP80000 per annum + + Benefits
Bramwith Consulting
Rapidly growing professional services firm seeks an experienced indirect procurement leader to join their procurement function during a period of exciting transformation and growth.
London, England
£50000.00 - £65000.00 per annum
Hays
Learning & Development Partner London - Hybrid £50000 - £65000
London, England
£50000.00 - £65000.00 per annum
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Leaning Manager - Technical Learning London £50000 - £65000
Andover, Hampshire
£70,000 - £85,000 p.a.
Harris Hill
Would you like to help shape our research strategy and help us become the funder we want to be? A leading charity focused on macular disease, the b...
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Langley Search & Interim
My Client is a leading organisation in their field. They are currently looking for a specialist Category Lead – Utilities/Energy with experience in...
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createselect
Looking for an SEO expert to join our fabulous client as Head of SEO.
London
£40k - 50k per year
Harris Hill
Sitting in the Operations team, you will understand the ins and outs of the Planning team, identify gaps and work with the full team to evolve these
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£55000.00 - £75000.00 per annum
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Regional HR Manager / HR Business Partner Chartered Accountants £55,000 - £75,000 DOE
City of London, London
£120000 - £900000 per annum
DNA Recruit
Are you are a Senior Planning Strategist or a Planning Director with experience in consumer and retail?Are you a natural leader who takes full respons
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GBP55000 - GBP65000 per annum + + Car & Benefits
Bramwith Consulting
Iconic FMCG brand seeks a high-achieving procurement expert to join the ranks and drive a crucial spend category towards best-in-class.
City of London
GBP80000 - GBP90000 per annum + + Package + Flexi Working
Bramwith Consulting
Global IT Vendor Lead - FTSE 50 Media Giant Salary: £60-70,000 plus package Location: London (flexible basis)
City of London
GBP55000 - GBP80000 per annum +
Bramwith Consulting
Indirect Procurement Generalist - Leading Consultancy - Flexible Working - Paid Travel Leading consultancy seeks an established procurement profession
England
GBP55000 - GBP65000 per annum + + Car + Flexi Working
Bramwith Consulting
Indirect Procurement Manager - Global prof Services Salary: £55-65,000 plus package + CIPS Sponsorship Location: Hertfordshire
London
GBP65000 - GBP80000 per annum +
Bramwith Consulting
Procurement Consulting opportunities - Market Leading Procurement Boutique Consultancy - Private Equity Backed - London + Travel - £65-80k + Package
London
GBP700 - GBP800 per day +
Bramwith Consulting
INTERIM - Global senior Procurement Manager - Market Data and Vendor Management - London - Global Financial Services Firm - £700-800pd Leading Europea
City of London
GBP55000 - GBP80000 per annum +
Bramwith Consulting
Indirect Procurement Generalist - Leading Consultancy - Flexible Working - Paid Travel Leading consultancy seeks an established procurement profession
London
GBP50000 - GBP65000 per annum +
Bramwith Consulting
Global Financial Services Major - Procurement supplier Governance and 3rd party risk - London - £55-60k + competitive financial package Global financi
London (Central)
£90k-£110k + bonus and benefits.
Premier Resourcing UK
Senior Counsel position with leading international communications agency. £110k + bonus/benefits.
Coventry, England
Up to £55000.00 per annum + Bonus & Benefits
Wright Solutions
This is an exciting opportunity to join a major UK business as a modern day and strategically minded HR Business Partner.
High Wycombe, England
£60000 - £65000 per annum + hybrid working, car allowance, bonus
Henlee Resourcing
Reporting to the Head of HR Business Partnering, the purpose of the role is to build great relationships with your Senior Stakeholders / Client Group to enable them to deliver on the Company vision as well as to continue the great work around belonging, t
London, England
£340.00 - £460.00 per day
Hays
Interim Contingent Hire Business Manager - +6 months - partially remote
Northamptonshire, England
£65000.00 - £75000.00 per annum + Car allowance, Private Medical
Hays
HR Systems Implementation Lead (12 month Fixed term contract) £65,000-£75,000 Northamptonshire
London
Up to £75000.00 per annum + £50,000 commission
Tomorrow Recruitment
Director of Growth and New Business for design agency
City of London, England
Up to £70000 per annum
Morgan Law
We are recruiting for an Interim HR Systems Lead, for an initial 2 year fixed term contract.
Lancashire, England
£71963.00 - £77257.00 per annum
Hays
As the Head of Human Resources, you will have a passionate belief in the role of high-quality HR services that enable and empower leaders and staff to transform outcomes for children and young people.
Kent, England
£400 - £500 per day + Outside IR35
Morgan Law
My client, a multi-academy trust based in Kent is looking for an HR Project Manager/Consultant to join them as they look to Boost on their HR System & Payroll offering across the trust.
Brighton, Sussex
circa £90,000
Harris Hill
Our organisation is looking for an inspirational and dynamic leader who shares our commitment to our mission and values, and to providing people-fi...
London/WFH
£80,000-£100,000 +equity
YOU Search & Select
This is a strategic development role for serious players. It’s why bullsh*tters need not apply.
Remote/London
£70,000-£90,000 +package
YOU Search & Select
Q. What do you call an exec producer who’s great at leading teams? A. Invisible. Why? As that’s the way you like it.
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GBP75000 - GBP80000 per annum + Benefits
Bramwith Consulting
Iconic brand seeks a high-achieving procurement expert to join the ranks and drive a crucial spend category towards best-in-class.
City of London
GBP60000 - GBP90000 per annum + Package
Bramwith Consulting
IT Procurement Lead - Hardware, Software & Telecoms - Global Consultancy - FTSE100 Blue-Chip Clientele - Fast-Track Progression - £60-90k + PackageGlo
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GBP70000 - GBP100000 per annum + Car & Bonus
Bramwith Consulting
Procurement Business Partner / Industry-Leading FMCG Organization / Transformation / practicing / Flexible Working / £70,000 - £100,000 + Benefits inc. Bonus & Car
London, England
£55000.00 - £60000.00 per annum
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Senior HR Advisor London - Hyrbid £55000 - £60000pa
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GBP500 - GBP700 per day + Remote Working
Bramwith Consulting
Indirect IT Procurement Manager / Industry-Leading Pharmaceutical organization / Remote Working / £600pd - £700pd
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GBP500 - GBP700 per day + Flexible Working
Bramwith Consulting
Indirect IT Procurement Manager / Global Financial Services / London / Flexible Working / Interim Position / £600 - £700pd
City of London
GBP45000 - GBP80000 per annum +
Bramwith Consulting
Indirect Generalist - Central London - Flexible Working - £45,000-£80,000 Bright and dynamic individuals sought by Leading Management Consultancy, bas
City of London, England
£55000.00 - £65000.00 per annum
Hays
Established Stock Exchange Listed Global Investment Management Firm
London
£75000 - £95000 per annum
Stonor
One of the UK's longest established, and most well-respected media groups is looking for a Head of Partnerships.
Anywhere in the UK
£54,600 per annum
Wildfowl & Wetland Trust
Head of UK Programmes Anywhere in the UK 37.5 hours a week £54,600 per annum This position can be undertaken anywhere in the UK but is ideally base...
Loughborough, Leicestershire
circa £85,000
Harris Hill
The national charity and leading voice for disabled people in sport and activity is looking for a new Chief Executive Officer (CEO) who can lead th...
Shrewley
£45k - 50k per year
Harris Hill
You will work collaboratively across the charity to ensure all communications are on brand, deliver key messaging and engage target audiences.
London, England
£50000.00 - £60000.00 per annum
Hays
HR Operations Partner London up tp £55000 - £60000pa
London, England
£50000.00 - £70000.00 per annum + Bonus, hybrid, negotiable
Hays
A fully autonomous Senior HRIS Specialist role, where you will have full ownership to design, implement, and bring to life an established but under utilised HRIS system.
Multiple UK Locations Available
Competitive
The HR Dept
Want to run your own HR business and be your own boss? The HR Dept's trusted brand and network supports you at every stage from setup to success.
London (Greater)
Up to £150'000 + benefits
Brook Street
Director (Financial PR - Tech, Natural Resources, Financial Services ). Leading Corporate & Financial PR Agency. Competitive Salary.
Homeworking
GBP50000 - GBP60000 per annum +
Bramwith Consulting
Procurement Category Specialist - Software & Data - Global Leading Law-Firm - London based + home working - £50-60k + packageThis leading global law f
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GBP55000 - GBP65000 per annum + + Package + Flexi Working
Bramwith Consulting
IT Procurement Manager - Public Sector - Global Professional Services Firm Salary: £55-65,000 + package Location: Remote (option to base yourself in office)
London (Central), London (Greater)
Circa £65,000 - £75,000
VMA Group
The Global Cement and Concrete Association, GCCA, is growing its team and looking for a seasoned Head of Media, content and engagement.
Dublin City Centre
EUR60000 - EUR90000 per annum + bonus + benefits
Bramwith Consulting
Strategic Sourcing Manager, IT & Technology - Global FTSE 100 FMCG Player - Dublin- £50,000 - €90,000 + Bonus & Benefits
Amsterdam
EUR60000 - EUR80000 per annum + package
Bramwith Consulting
IT Procurement Team Lead - Global FTSE 100 Conglomerate - Amsterdam - €80,000 + Package
Dublin City Centre
EUR55000 - EUR90000 per annum + bonus + benefits
Bramwith Consulting
Software Technology Procurement Manager - Strategic Growth Initiative - £25bn+ Professional Services Giant - DUBLIN
Dublin
EUR60000 - EUR80000 per annum + package
Bramwith Consulting
PROCUREMENT - GLOBAL HR/PROFESSIONAL SERVICES CATEGORY MANAGER - ICONIC FTSE 100 PROFESSIONAL SERVICES FIRM - DUBLIN+ FLEX WORKING - €85,000 + COMPREHENSIVE BENEFITS
London, England
£60000.00 - £70000.00 per annum
Hays
Interim HR Manager - Immediate start - 10 month FTC - London Hybrid - £60-70k pro rata
Nottingham, England
£40927.00 - £50296.00 per annum
Hays
HR Business Partner - Education - 6 month FTC - Flexible & hybrid working - up to £50296
London client, can be based 100% home based
up to £450 per day (inside IR35)
Langley Search & Interim
Interim FM Contract Manager opportunity, initially assignment likely to be until the end of the year, £450 per day (inside IR35), London based clie...
London
GBP75000 - GBP85000 per annum +
Bramwith Consulting
Logistics Category Manager - Global FMCG Major - £75-85,000 + Excellent Benefits Package -Home Working Following a transformation of their global com
London, England
£48997.00 - £68790 per annum + Civil Service Pension
Morgan Law
Fantastic opportunity for an experienced Leadership Development specialist to join the UK's largest Police Service.
London
£90000 - £110000 per annum
Major Players
I am working with a leading global creative and media agency, who specialise in social-first advertising, building brands up through digital platforms
Hybrid working with regular weekend and evening working
£108,000
Samaritans
We are looking for a strategic and collaborative leader who will lead the development and drive the People Strategy.
London
£80000 - £90000 per annum + + bens
Major Players
Leading UK agency are looking for an Experience Designer (XD) with world-class creativity & ability to bring real, relevant human insights into commu
London (Central), London (Greater)
up to £100k
Corporate Communications Recruitment
An award winning global integrated agency with a strong corporate branding offer are looking to hire a head of brand strategy. Great opportunity!
Homeworking
GBP55000 - GBP65000 per annum + + Car & Benefits
Bramwith Consulting
Iconic FMCG brand seeks a high-achieving procurement expert to join the ranks and drive a crucial spend category towards best-in-class.
Elizabeth
USD90000.00 - USD100000 per annum +
Bramwith Consulting
HR & Professional Services Procurement Specialist - Fortune 100 FMCG - Elizabeth - New Jersey - $100,000 + Package Global FMCG seeks an ambitious procurement specialist to join their team in a newly created role to support the development of thei
London
GBP75000 - GBP85000 per annum +
Bramwith Consulting
Procurement Category Manager - Logistics - Big4 Consultancy - London/WFH - £85,000 + £6,000 car 12% bonus and other benefits One of the world largest
London
GBP55000 - GBP70000 per annum +
Bramwith Consulting
Global Category Specialist (indirects) - Esteemed Professional Services Firm - £65k - Multiple Locations - Global Sourcing As one of the most recognis
London, East London
£75000 - £85000 per annum
Major Players
Job Title - Client Services Director The Role / Company Major Players are working with a retail design and production agency who provide retail activa
London, England
£300.00 - £450.00 per day
Hays
Interim Benefits Manager EMEA - Financial services - London Hybrid £300-450 per day inside scope of IR35
Wakefield, England
£44000 - £59000.00 per annum + no site parking , flexible working
Hays
An intersting mix of strategic & operational HR , you will lead a small HR team on a day-day basis.
London, SE22 8RB
£55,602 - £65,599
Charter Schools Educational trust
Are you an experienced, self-motivated, and ambitious Human Resources leader looking to make an impact in a growing and thriving Multi-Academy Trus...
Hybrid working: Home working / Marleigh, Cambridge
c £70,000
Anglian Learning
Anglian Learning Director of People Location: Hybrid working: Home working / Marleigh, Cambridge Salary: c £70,000 Closing date: Monday 5th Septemb...
City of London, England
£400.00 - £600.00 per day
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Interim D&I Manager EMEA - 6 months London hybrid, day rate inside scope of IR35 Option for remote working in the UK
City of London, England
£200.00 - £250.00 per day
Hays
Interim HR Advisor - Immediate start - Financial services - London Hybrid c£200-250 per day
Leeds, London or Sheffield
Up to £85,000
Department for Work and Pensions
Department for Work and Pensions Deputy Director, Head of Campaigns Salary: Up to £85,000 Location: This role can be based any of the following DWP...
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£195.00 - £210.00 per day
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3 month HR Policy interim, for a membership organisation in London, paying £195-210 per day, starting ASAP.
London, England
£300.00 - £350.00 per day
Hays
6 month Interim Compensation Advisor role, paying £300-350 per day, starting ASAP.
Blackburn, England
£71963.00 - £77257.00 per annum + excellent pension
Hays
We have an exciting opportunity for an experienced HR professional to join one of the country's highest performing and fastest growing multi academy trusts, currently operating over 30 primary and secondary schools nationally.
London, England
Up to £52485 per annum
Hays
Permanent L&D Consultant role with a trade union in London hybrid working 2 days per week paying up to £52,485.
London (Central), London (Greater)
up to £100k
Corporate Communications Recruitment
Communications agency are looking to hire a business relationship director to lead their team across their media coaching and comms offer! Urgent!
London (Central), London (Greater)
circa £70k
Corporate Communications Recruitment
Communications agency are looking to hire a Sustainability consultant. Ideally you will have agency/consultancy and communications experience.
London (Central), London (Greater)
up to £70k
Carter Ferris
A fantastic opportunity to effectively launch a new inhouse PR division within this high profile, high talent London based creative agency. You wil...
London (Central), London (Greater)
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Cake Distribution Limited
An exciting new opportunity has arisen with in CAKE a leading independent kids and family content distribution and TV production company.
City of London, England
£60000.00 - £90000.00 per annum
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Senior Talent Acquisitions Partner within Technology in a Leading Fortune 500 Tech Solutions Firm
Northampton, England
£50000.00 - £60000.00 per annum + Car allowance-£7,000
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Permanent HR Manager, Northampton-Hybrid-£50,000-£60,000 + £7,000 car allowance.
Winchester, England
£22.99 - £25.25 per hour
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HR Analyst / Workforce Analyst / HR Systems
Bournemouth, England
£17.00 - £25.00 per hour
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HR System Project Analyst to support a implementation project team on an interim basis
London (Central), London (Greater)
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ITN
This role is responsible for managing all aspects of publicity for award-winning news programme, Channel 4 News, and associated digital platforms. ...
London, England
£50000.00 - £70000.00 per annum
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Interim Reward/Compensation Analyst- £55-£65k - London - Hybrid - 9 Months FTC
London (Central), London (Greater)
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Barker Graves
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The Foundry - Original
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c£150,000 plus comprehensive benefits
The Foundry - Original
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£65,000-£75,000 + package
YOU Search & Select
I honestly thought these types of roles had disappeared. Lost to a time when customer care and trusted client partner actually meant something...
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£90000.00 - £110000.00 per annum
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Head of Human Resources - International Bank - £90,000 - £110,000 - Dependant on experience
City of London, England
£200.00 - £250.00 per day
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Interim HR Advisor - Immediate start - Financial services - London Hybrid c£200-250 per day
City of London, England
£450 - £500 per day
Morgan Law
We are seeking an interim EDI Consultant to work with a global marine conservation charity.
City of London, England
Up to £500 per day
Morgan Law
We are seeking an experienced Reward Consultant, to work for a global charity.
London (Central)
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Premier Resourcing UK
Associate Director – Consumer/FMCG GV5399 Based in central London, this multi-award winning agency who are growing quickly with a great team, are ...
Dorchester, England
£25.31 - £27.84 per hour
Hays
Interim Recruitment Advisor / Internal Recruiter
London (Central), London (Greater)
to £70k + great benefits
Fill Recruitment
Digitally led agency seeks Midweight or Senior Strategist for a rare role with unrivalled variety - to £70k
London (Central), London (Greater)
£60,000 - £80,000 + bens package
Ann Sharman Consulting
Are you Senior Strategist looking for the next step up? Iconic Global Strategy Consultancy seeks an Associate Directory of Strategy with a b2b focus.
Cancer of the uterine cervix has become a growing public health challenge with increasing mortality and morbidity among women in lower human development index countries.1 It is reported as the foremost and fourth most common cause of cancer deaths among women.2,3 Bray et al2 reported estimated global new cases of 569,847 (3.2%) and a mortality of 311,365 (3.3%) in 2018. Low- and middle-income countries account for one of the highest prevalence of cervical cancer, with an estimated 90% of global deaths occurring in this region. Cancer of the uterine cervix is the second leading female cancer among Nigerian women, after breast cancer,4 and accounts for more than 10,000 annual deaths.2,5
CONTEXT
-
Key Objective
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What are men and women's knowledge and screening practices of cervical cancer in urban slum community settings?
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Knowledge Generated
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The mean knowledge score of cervical cancer detection was 5.0 ± 2.6 on a 0- to 39-point scale. Cervical cancer prevention practices (screening and human papillomavirus vaccination) were very low.
-
Relevance
-
Low knowledge potentially translates to low practice, as shown in this study. These may result in late detection and presentation at health facilities with poor treatment outcomes. Prevention strategies, at primary and secondary levels, including educational interventions should be encouraged in clinical and other settings to prevent an overburdening of the health system.
The major cause of cervical cancer is the human papillomavirus (HPV), and the disease is sexually transmitted. Other risk factors include high parity, smoking, sexual initiation at an early age, multiple sexual partners, and prolonged use of oral contraceptives. The prevention rate for cervical cancer is high if detected and treated early.6 The WHO recommends regular screening every 3-5 years among women age 30-49 years, in addition to timely treatment of precancerous lesions.2 More recently, the World Health Assembly endorsed the WHO Global Strategy for elimination of cervical cancer. The global targets for 2030 emphasize primary prevention (90% coverage of HPV vaccination of girls by age 15 years) and secondary prevention (70% of women to be screened by age 35 and 45 years).7
Vaccination is reported as an important public health primary prevention approach to reduce the risk of HPV, whereas cervical cytology or Papanicolaou test (Pap smear) is documented as secondary form of prevention.8 In Nigeria, primary prevention through HPV vaccination is not yet part of the national routine immunization program; it is, however, accessible, at a high cost, through a limited number of private and public health care settings. Conventionally, secondary prevention through screening is carried out in Nigeria using Pap smear test.9 However, Pap smear test is not suitable as primary screening in low-resource settings although it has played a substantial role in reducing cervical cancer in developed countries over the past 70 years. Awareness and knowledge of cervical cancer are, however, necessary for improved involvement of women in prevention and screening practices. Several studies have been carried out among Nigerian women to assess the knowledge and screening practices for cervical cancer (including HPV vaccine and Pap smear test) and among HIV-infected women. Most studies have shown an appreciable high knowledge of cervical cancer in urban workplace settings, women attending health facilities, or health workers. Conversely, many studies have documented low knowledge and practice among women,1,10,11 especially at population levels. Incessant creation of awareness about cervical cancer has the potential to increase knowledge and utilization of cervical cancer screening practices.12 More research documenting both men's and women's knowledge of cervical cancer and screening practices among women in urban slum community settings is needed. Focus on men in addition to women on cervical cancer studies is very scanty in Nigeria. Thus, the inclusion of men, and not only women, is important because of the decision-making role of men in Nigerian families and in improving family health. This study therefore investigated the knowledge and screening practices for cervical cancer among male and female adults in urban poor settings in Ibadan, Nigeria. The findings from this study would inform baseline data for planning appropriate health promotion and education, prevention interventions, and policy formulation to prevent and control cervical cancer in poor community settings in Nigeria.
Study Design and Setting
This study used a cross-sectional design in two urban community-based settings in Ibadan, Oyo State, Nigeria. Data collection lasted for 3 weeks in both communities. Ibadan is the largest city in Africa situated in the western region of Nigeria. Ibadan has a population of 3 million and is a combination of both urban and semiurban community settings. Two underserved communities located in the urban slum areas of Ibadan North Local Government Areas (LGAs) were identified. The two communities selected for this study are at the heart of Ibadan city in an urban LGA but have a mixture of higher- and lower-educated people and subsequently a combination of high-, middle-, and low-income communities. The LGA has an estimated population of 308,119, and sanitary conditions in the slum areas are poor as the majority of houses do not have access to potable water and water-flushed toilets.
Study Population, Sampling, and trial Size
All consenting male and female adults in both communities age 18-65 years were eligible to participate in this study. Exclusion criteria included persons who did not provide consent to participate in the study and physically or mentally ill men and women, who were unable to provide adequate information. A previous community-based study by Nnodu et al13 informed the calculation of the trial size of 500, using the Leslie Kish formula. The prevalence of knowledge about HPV was 33%, with calculations on the basis of 95% confidence level, a margin of error of 5%, and a design effect of 1.5. The final trial size calculated was 334, but to cater for attrition and to cover a larger trial area, the trial size was increased to 500. Community members age 18-65 years were randomly selected from the total community population. Simple random sampling technique was used to select participating households, whereas one respondent was selected in each household by ballot to avoid selection bias. A total of 147 males and 353 females completed the electronic data.
Data Collection Methods and Instruments
The research team had earlier visited and interacted with the communities' stakeholders including the heads of the landlord association, executives of the association, and religious leaders. The two communities had committed to support the study and paved the way for easy connection to the community members. In the two communities, 552 people were approached and only 52 declined to participate, mostly because they had to engage with other commitments at the time of the interview. Most of those who consented to participate were self-employed so could create time for the interview.
Data collection instrument was developed and converted into an electronic data capture tool (ODK Collect). Data collection was interviewer administered using the translated instrument into the local language Yoruba and back-translated to English for content validity. Data tool contained both open- and closed-ended questions (Data Supplement). Interviewers were trained before data collection process to ensure increased quality of data set, and all followed a homogenous procedure. Data were pretested in similar community settings before real data collection was undertaken. The ODK tool included questions on sociodemographic characteristics of respondents and cervical cancer questions on awareness and knowledge of cervical cancer risk factors, symptoms, and detection. Questions were also asked about screening practices with Pap smear, visual inspection with acetic acid, reasons for nonscreening, and HPV vaccination. Respondents were asked to identify their responses to knowledge questions with yes or no as appropriate. Open-ended question responses were recorded on the ODK tool by interviewers. Knowledge questions were scored (on a scale of 0-39) for respondents' knowledge of cervical cancer detection, symptoms, and risk factors. Total scores were added together, and a mean knowledge score for respondents was calculated.
Quality Assurance
Throughout the data collection process, research assistants were monitored and gave daily feedback on the research process. The electronic data collected were uploaded daily and checked for completeness and errors. In those cases where there were errors, research assistants were asked to collect additional data and the data previously collected were discarded. Quality assurance meetings were held weekly to review the data collected, weekly targets, and any challenges that research assistants encountered. This enabled immediate response to facilitate ease of data collection procedure.
Data Analysis
Electronic data collected using the ODK tool were checked before they were transferred into the Statistical Package for Social Sciences (IBM SPSS) version 21. Both descriptive and inferential statistics analyses were used to meet the criteria of the study objectives. Categorical variables were presented using frequencies and percentages, whereas continuous variables reported means and standard deviations. Inferential statistics was obtained using chi-square statistics to estimate the degree of association between the variables in the study. Multivariate regression analysis was not carried out because there was no statistical significance from the chi-square statistics.
Ethical Consideration
The study protocol was approved and informed (by signing an informed consent form), and voluntary consents were sought and obtained from community leaders, stakeholders, and all study respondents, before the commencement of data collection (Data Supplement). There were no physical risks to the respondents; data were collected in privacy, and respondents were assured that they would not be penalized in any way if they chose to stop the data collection at any stage. Respondents were assured of confidentiality of responses, and only identification codes were assigned to ODK files. Study findings were disseminated to participating communities after the completion of the study.
The study protocol was approved by the University of Ibadan/University College Hospital Nigeria Ethical Review Committee, Nigeria, with the reference number UI/EC/17/0410.
Socioeconomic Characteristics of Respondents
A majority of respondents were females (70.6%), and the mean age was 35.36 ± 12.24 years. More than half (52.6%) of the respondents had completed secondary school education, with most numerous ethnic group among them being Yoruba (88.8%). A majority (64.0%) of respondents were married, and the most predominant religions were Christianity (51.0%) and Islam (49.0%). A majority of respondents (72.6%) were self-employed with small-scale business. Many (67.2%) had a monthly income of 20,000 naira ($51 US dollars) or less. More than half of the respondents (54.8%) had a household size of two to four people, whereas 37.0% had more than five members (Table 1).
Awareness of Cervical Cancer
A majority of respondents were not aware of cervical cancer screening (91.2%) and Pap smear test (93.6%). Few (10%) had ever heard of HPV vaccine for the prevention of cervical cancer.
Knowledge of Cervical Cancer (detection, symptoms, and risk factors)
The knowledge of the risk factors for cervical cancer showed that majority (92.4%; 0.92 ± 0.27) reported that old age, low socioeconomic status (88%; 0.88 ± 0.33), unhealthy diet (75.8%; 0.76 ± 0.43), and high rate of abortion (73%; 0.73 ± 0.44) were risk factors for cervical cancer (Table 2).
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A majority of respondents (91.60%; 0.92 ± 0.28) reported that the absence of menstruation or irregular menstruation, itching at the vagina (91.00%; 0.91 ± 0.29), and painful menstruation (95.40%; 0.95 ± 0.21) constitute symptoms of cervical cancer (Table 2).
The results of knowledge on detection of cervical cancer showed less than half (41.4%; 0.41 ± 0.49) of the respondents reported that cervical cancer can be terminal. However, a majority of respondents (88.6%; 0.89 ± 0.32) reported that it is sufficient to only do cervical cancer test once to eliminate its risk, and 83.4% (0.83 ± 0.37) reported that cervical cancer is a genetic disease, whereas 92.6% (0.93 ± 0.26) reported that postmenopausal women still have the risk of getting cervical cancer.
The mean knowledge score of cervical cancer detection was 5.0 ± 2.6 with a minimum knowledge score of two and a maximum of 13, the mean knowledge score of cervical cancer symptoms was 3.3 ± 0.8 with a minimum knowledge score of one and a maximum of eight, and the mean knowledge score of risk factors for cervical cancer was 6.7 ± 1.6 with a minimum knowledge score of three and a maximum of 13. The overall knowledge of participants was pooled and assessed on a (0-39) point scale. This was further categorized into ranges with 0-18 points as poor knowledge, 19-23 points as fair knowledge, and 24-39 points as good knowledge of cervical cancer. Respondents' overall mean knowledge score was 15.0 ± 4.1. Majority (77.2%) had low knowledge score for cervical cancer.
There was a statistically significant association between knowledge of cervical cancer and employment status of respondents (χ2 = 10.35; P < .05). There was no statistically significant difference between knowledge and sex (Table 3).
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Cervical Screening Practices
Only women (n = 353) reported about cervical cancer practices. Very few women had been screened for cervical cancer with the Papanicolaou test (4%), and one woman with visual inspection with acetic acid (0.3%). Four women had taken HPV vaccine before (1.1%) (Table 4).
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The overall results of this study indicated low knowledge of cervical cancer and screening practices. The study findings revealed a considerable proportion of the respondents to have had either secondary or tertiary education. Average to high level of education did not seem to translate to awareness or good knowledge of cervical cancer among the study respondents. This was in contrast to findings reported by Ezenwa et al10 among women in similar urban community settings in Nigeria. Importantly, findings highlighted low socioeconomic status on the basis of low income of respondents with majority living on 20,000 naira or less per month (equivalent of 51 dollars per month), and moreover, majority were self-employed with petting trading. This translates to less ability to afford the cost of screening or vaccination for the prevention of cervical cancer, coupled with lack of accessibility. This result was similar to the findings of Olanlesi-Aliu et al14 on the quality of services on cervical cancer being affected by inadequate resources. Subsequently, the employment status was a variable that could exert influence on knowledge of the respondents on cervical cancer.
Poor level of awareness was reported for cervical screening, Pap smear, and HPV vaccine from the results of this study. Previous research findings13,15 corroborated these outcomes. These findings consequently demonstrate a need for increased awareness on cervical cancer, HPV screening, and vaccination, as well as the need for health promotion and education strategies targeting cervical cancer screening and the benefits of vaccination among adults in poor urban community settings in Nigeria. Almost all the knowledge scores for questions on risk factors, symptoms, and detection for cervical cancer had responses below the average. This is suggestive of perceived low susceptibility to the disease, but strikingly, majority perceived postmenopausal women to still have the risk of getting cervical cancer, whereas mean score was high for testing is only needed once to eliminate the risk of cervical cancer. Knowledge gaps among study respondents highlight a crucial need for health education to increase knowledge about cervical cancer. Health education should include recommendations for screening, according to the ACOG. The ACOG highlighted that women age between 25 and 29 years are recommended for cervical cytology or Pap test only at 3-year intervals, whereas those who are 30 years to 65 years could have a combination or cotesting of Pap test and HPV test every 5 years. For women over 65 years, screening can be halted on the basis of acceptable previous negative screening within the past 5 years.16
This study highlights major gaps in prevention practices for cervical cancer and identifies an urgent need to upscale cervical cancer prevention and intervention strategies in urban poor community settings of Nigeria. Findings are similar to a accurate study carried out among women,1 where only two women had gone through cervical cancer screening test, but none of them had taken HPV vaccination. These findings are reflective of the inadequate health programs and services regarding cervical cancer prevention in Nigeria.14
In conclusion, the findings of this study have underscored a necessity for increased awareness creation through health promotion interventions and strategies to alleviate low knowledge of cervical cancer, prevention, and screening practices in poor community settings in Nigeria. The provision of prevention services, which must be accessible and affordable to the populace irrespective of the geographical location, is also needed.
PRIOR PRESENTATION
Presented at the 7th Annual Symposium on Global Cancer Research: Translating and Implementation for Impact in Global Cancer Research, Chicago, IL, March 7, 2019. This study abstract has been published in J Global Oncol 2019:3. © 2019 by American Society of Clinical Oncology following international conference/symposium presentation and can be found here: DOI: 10.1200/JGO.19.10000.
SUPPORT
Supported by a planning grant awarded by the US National Institutes of Health, Fogarty International Center, Addressing NCDs In Nigeria Through Enhanced International Partnership and Interdisciplinary Research Training, award number 1D71TW010876-01.
Conception and design: All authors
Administrative support: All authors
Provision of study materials or patients: All authors
Collection and assembly of data: All authors
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The following represents disclosure information provided by the authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
No potential conflicts of interest were reported.
We acknowledge all the respondents and research assistants for their contributions to the conduct of the study. We are grateful to the ethical committee who provided approval for this study.
| 1. | Olubodun T, Odukoya OO, Balogun MR: Knowledge, attitude and practice of cervical cancer prevention, among women residing in urban slum in Lagos, South West, Nigeria. Pan Afr Med J 32:130, 2019 Crossref, Medline, Google Scholar |
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The venerable ATX standard was developed in 1995 by Intel, as an attempt to standardize what had until then been a PC ecosystem formed around the IBM AT PC’s legacy. The preceding AT form factor was not so much a standard as it was the copying of the IBM AT’s approximate mainboard and with it all of its flaws.
With the ATX standard also came the ATX power supply (PSU), the standard for which defines the standard voltage rails and the function of each additional feature, such as soft power on (PS_ON). As with all electrical appliances and gadgets during the 1990s and beyond, the ATX PSUs became the subject of power efficiency regulations, which would also lead to the 80+ certification program in 2004.
Starting in 2019, Intel has been promoting the ATX12VO (12 V only) standard for new systems, but what is this new standard about, and will switching everything to 12 V really be worth any power savings?
What ATX12VO Is
As the name implies, the ATX12VO standard is essentially about removing the other voltage rails that currently exist in the ATX PSU standard. The idea is that by providing one single base voltage, any other voltages can be generated as needed using step-down (buck) converters. Since the Pentium 4 era this has already become standard practice for the processor and much of the circuitry on the mainboard anyway.
As the ATX PSU standard moved from the old 1.x revisions into the current 2.x revision range, the -5V rail was removed, and the -12V rail made optional. The ATX power connector with the mainboard was increased from 20 to 24 pins to allow for more 12 V capacity to be added. Along with the Pentium 4’s appetite for power came the new 4-pin mainboard connector, which is commonly called the “P4 connector”, but officially the “+12 V Power 4 Pin Connector” in the v2.53 standard. This adds another two 12 V lines.
In the ATX12VO standard, the -12 V, 5 V, 5 VSB (standby) and 3.3 V rails are deleted. The 24-pin connector is replaced with a 10-pin one that carries three 12 V lines (one more than ATX v2.x) in addition to the new 12 VSB standby voltage rail. The 4-pin 12 V connectors would still remain, and still require one to squeeze one or two of those through impossibly small gaps in the system’s case to get them to the top of the mainboard, near the CPU’s voltage regulator modules (VRMs).
While the PSU itself would be somewhat streamlined, the mainboard would gain these VRM sections for the 5 V and 3.3 V rails, as well as power outputs for SATA, Molex and similar. Essentially the mainboard would take over some of the PSU’s functions.
Why ATX12VO exists
The folk over at GamersNexus have covered their research and the industry’s thoughts on the course of ATX12VO in an article and video that were published last year. To make a long story short, OEM system builders and systems integrators are subject to pretty strong power efficiency regulations, especially in California. Starting in July of 2021, new Tier 2 regulations will come into force that add more strict requirements for OEM and SI computer equipment: see 1605.3(v)(5) (specifically table V-7) for details.
In order to meet these ever more stringent efficiency requirements, OEMs have been creating their own proprietary 12 V-only solutions, as detailed in GamersNexus’ recent video review on the Dell G5 5000 pre-built desktop system. Intel’s ATX12VO standard therefore would seem to be more targeted at unifying these proprietary standards rather than replacing ATX v2.x PSUs in DIY systems. For the latter group, who build their own systems out of standard ATX, mini-ITX and similar components, these stringent efficiency regulations do not apply.
The primary question thus becomes whether ATX12VO makes sense for DIY system builders. While the ability to (theoretically) increase power efficiency especially at low loads seems beneficial, it’s not impossible to accomplish the same with ATX v2.x PSUs. As stated by an anonymous PSU manufacturer in the GamersNexus article, SIs are likely to end up simply using high-efficiency ATX v2.x PSUs to meet California’s Tier 2 regulations.
Evolution vs Revolution
Ever since the original ATX PSU standard, the improvements have been gradual and never disruptive. Although some got caught out by the negative voltage rails being left out when trying to power old mainboards that relied on -5 V and -12 V rails being present, in general these changes were minor enough to incorporate these into the natural upgrade cycle of computer systems. Not so with ATX12VO, as it absolutely requires an ATX12VO PSU and mainboard to accomplish the increased efficiency goals.
While the possibility of using an ATX v2.x to ATX12VO adapter exists that passively adapts the 12 V rails to the new 10-pin connector and boosts the 5 VSB line to 12 VSB levels, this actually lowers efficiency instead of increasing it. Essentially, the only way for ATX12VO to make a lot of sense is for the industry to switch over immediately and everyone to upgrade to it as well without reusing non-ATX12VO compatible mainboards and PSUs.
Another crucial point here is that OEMs and SIs are not required to adopt ATX12VO. Much like Intel’s ill-fated BTX alternative to the ATX standard, ATX12VO is a suggested standard that manufacturers and OEMs are free to adopt or ignore at their leisure.
Important here are probably the obvious negatives that ATX12VO introduces:
- Adding another hot spot to the mainboard and taking up precious board space.
- Turning mainboard manufacturers into PSU manufacturers.
- Increasing the cost and complexity of mainboards.
- Routing peripheral power (including case fans) from the mainboard.
- Complicating troubleshooting of power issues.
Add to this potential alternatives like Seasonic’s CONNECT module. This does effectively the same as the ATX12VO standard, removing the 5 V and 3.3 V rails from the PSU and moving them to an external module, off of the mainboard. It can be fitted into the area behind the mainboard in many computer cases, making for very clean cable management. It also allows for increased efficiency.
As PSUs tend to survive at least a few system upgrades, it could be argued that from an environmental perspective, having the minor rails generated on the mainboard is undesirable. Perhaps the least desirable aspect of ATX12VO is that it reduces the modular nature of ATX-style computers, making them more like notebook-style systems. Instead, a more reasonable solution here might be that of a CONNECT-like solution which offers both an ATX 24-pin and ATX12VO-style 10-pin connectivity option.
Thinking larger
In the larger scheme of power efficiency it can be beneficial to take a few steps back from details like the innards of a computer system and look at e.g. the mains alternating current (AC) that powers these systems. A well-known property of switching mode power supplies (SMPS) like those used in any modern computer is that they’re more efficient at higher AC input voltages.
This can be seen clearly when looking for example at the rating levels for 80 Plus certification. Between 120 VAC and 230 VAC line voltage, the latter is significantly more efficient. To this one can also add the resistive losses from carrying double the amps over the house wiring for the same power draw at 120 V compared to 230 VAC. This is the reason why data centers in North America generally run on 208 VAC according to this APC white paper.
For crypto miners and similar, wiring up their computer room for 240 VAC (North American hot-neutral-hot) is also a popular topic, as it directly boosts their profits.
Future Outlook
Whether ATX12VO will become the next big thing or fizzle out like BTX and so many other proposed standards is hard to tell. One thing which the ATX12VO standard has against it is definitely that it requires a lot of big changes to happen in parallel, and the creation of a lot of electronic waste through forced upgrades within a short timespan. If we consider that many ATX and SFX-style PSUs are offered with 7-10 year warranties compared to the much shorter lifespan of mainboards, this poses a significant obstacle.
Based on the sounds from the industry, it seems highly likely that much will remain ‘business as usual’. There are many efficient ATX v2.x PSUs out there, including 80 Plus Platinum and Titanium rated ones, and Seasonic’s CONNECT and similar solutions would appeal heavily to those who are into neat cable management. For those who buy pre-built systems, the use of ATX12VO is also not relevant, so long as the hardware is compliant to all (efficiency) regulations. The ATX v2.x standard and 80 Plus certification are also changing to set strict 2-10% load efficiency targets, which is the main target with ATX12VO.
What would be the point for you to switch to ATX12VO, and would you pick it over a solution like Seasonic CONNECT if both offered the same efficiency levels?
(Heading image: Asrock Z490 Phantom Gaming 4SR with SATA power connected, credit: c’t)
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The framework to implement genomics-driven therapeutic oncology has been rapidly established in leading cancer centers worldwide. An exponential growth in characterized cancer genomes has ensued.1 The results of next-generation sequencing (NGS) assays are intricate and provide a multitude of somatic mutations in hundreds of genes. Mutation rates vary significantly between different cancers.2 Many somatic genetic variants are characterized as variants of unknown significance, and the implication of multiple mutations within a single tumor is poorly defined.3 Moreover, tumors possess intratumoral genetic heterogeneity, adding another layer of complexity to NGS results.4
CONTEXT
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Key Objective
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Algorithms to interpret the pathogenicity and clinical actionability of next-generation sequencing (NGS)–detected sequence variants have been implemented; however, little is known about their relative performance in clinical practice. The clinical interpretation of genomic alterations remains a major bottleneck for realizing precision medicine. We sought to examine the concordance for pathogenicity and clinical actionability of three annotation services available to the VA Precision Oncology Program (N-of-One, OncoKB, and Watson for Genomics).
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Knowledge Generated
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We demonstrate that NGS annotation services have wide-ranging agreements in pathogenicity (30%-76%). Moreover, there was moderate agreement (96.9%) in level 1 drug actionability.
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Relevance
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We anticipate these findings will encourage improvement in the precision of NGS multigene panel annotation. We provide detailed information regarding NGS panels, gene variant pathogenicity, annotation ontology, and level 1 drug actionability by annotation service. This study has significant implications for precision oncology clinical trials and molecular tumor boards.
At many institutions, including the Veterans Affairs (VA) healthcare system, molecular tumor boards (MTBs) have been instituted to interpret the results of NGS and develop treatment recommendations. In some instances the whole genome is sequenced, and in other cases selected subsets of genes are sequenced with smaller panels. Identified alterations that are of particular clinical interest include driver mutations or druggable mutations.1 For use in clinical decision making, identified gene variants must be annotated or interpreted in terms of the likelihood of their tumorigenicity and drug actionability.5 There are many resources to assist with data curation, including OncoKB (Memorial Sloan Kettering Cancer Center, New York, NY),6 My Cancer Genome (Vanderbilt-Ingram Cancer Center, Nashville, TN),7 Precision Medicine Knowledge Base (Weill Cornell Medicine Englander Institute for Precision Medicine, New York, NY),8 Personalized Cancer Therapy (MD Anderson Cancer Center, Houston, TX),9 CIViC (Washington University in St Louis School of Medicine, St Louis, MO),10 Jackson Laboratory Clinical Knowledgebase (Jackson Laboratory, Bar Harbor, ME),11 Cancer Genome Interpreter (Barcelona, Spain),5 Cancer Driver Log (omicX, Le-Petit-Quevilly, France),12 and N-of-One (NoO; Concord, MA).13 The identification of mutations that are pathogenic and actionable is generally performed by multidisciplinary teams who reference genomic databases, published literature, and clinical trials. The development of cognitive computing, such as Watson for Genomics (WfG), has also garnered interest in precision oncology. WfG14 is a cloud-based service that uses computerized models to simulate human thought to analyze large volumes of genome data and generate evidence-based guidelines.
The ultimate objective of gene sequencing is to Boost patient outcomes by matching patients to specific treatments that target mutations driving the growth of individual tumors. The landscape of genetic tests has evolved from single mutation to small hotspot mutation panels, large gene panels, and whole exome and whole genome platforms. The interpretation of the clinical significance of these genomic mutations has become a formidable task because of the number of genes tested and limited understanding of normal genetic variation as well as pathogenic gene-to-gene interaction. Although professional societies have recently published consensus guidelines15 for the use and interpretation of NGS, they have not been extensively used in practice. Moreover, traditional clinical trial design approaches of molecularly unselected tumor types may no longer be appropriate because of the molecular heterogeneity of tumors from each primary site (eg, breast). This has led to the development of basket and umbrella trial designs as well as precision genomic oncology trials at the point of care. An urgency exists to examine the various annotation services and clinical support tools available to ensure quality of NGS in oncology.
The VA National Precision Oncology Program (NPOP)16 initially used two commercial vendors for NGS testing, Personal Genome Diagnostics (PGDx, Baltimore, MD) and Personalis (Menlo Park, CA), that used the NoO commercial annotation service. In addition, WfG was available to the VA through a gift from IBM. Until NPOP accrues substantial outcomes data, treatment recommendations are largely based on biomarker panels, annotations, and relevant patient characteristics.17 NPOP also references open data sources, including OncoKB (an evidence source, not an annotation provider), when interpreting pathogenicity and actionability of gene variants. For some variants and cases, annotation is assisted by a molecular pathologist. The primary objective of this study was to assess the concordance for pathogenicity determination and clinical actionability for the annotation services available to NPOP.
Sequencing data from all patients who underwent NGS testing under NPOP since its genesis in 2015 through 2017 were analyzed. The work described here was conducted to assess the quality of annotation services available to the NPOP, a clinical operational program that is not research and does not require institutional review board review; permission to publish was obtained from the appropriate VA authority. Details of the NPOP have been published previously.16 The goal is to use NGS testing to facilitate patient access to US Food and Drug Administration (FDA)–approved targeted therapies and immune checkpoint inhibitors and increase participation in clinical trials (Data Supplement). Clinical trials have been the recommended option in > 50% of cases for which there was no FDA-approved therapy. NGS results were generated through two contracted vendors: PGDx18 (CancerSELECT 125, PlasmaSELECT 64, CancerSELECT 88, and CancerSELECT 203) and Personalis (ACE Cancer Plus 181)19 (Data Supplement).
We matched gene variants for the two contracted vendors, PGDx and Personalis, to compare vendor recommendations as well as commercial annotation services for the same unique gene variant. NGS-detected variants were annotated by the sequencing vendor using the commercial annotation service NoO. We examined NoO as implemented by the vendors. NPOP staff re-annotated DNA sequence results using WfG and OncoKB. IBM donated use of WfG to the VA; OncoKB is created and maintained by Memorial Sloan Kettering Cancer Center (MSKCC) and available online.6
After completion of sequencing, results were uploaded by an NPOP data scientist to WfG (including tumor type, a list of sequence variants as a variant call file, presence of gene fusions, and gene copy number variation). Results were routinely uploaded into WfG as part of routine test interpretation workflow. Batch analysis was performed approximately weekly using a custom-built informatics workflow and a packaging tool provided by IBM. WfG assigned a pathogenicity label to each variant or fusion. Drug matching for pathogenic variants is also part of the WfG analysis pipeline. Variants that are pathogenic or likely pathogenic are matched with FDA-approved drugs and actively recruiting clinical trials using levels of evidence (level 1, 2A, 2B, 3A, 3B, 4, or R1; Tables 1 and 2).3 For actionability, WfG uses a subset of National Cancer Institute (NCI) thesaurus terms for diagnosis coding.20 WfG was performed on all samples as part of NPOP workflow, and OncoKB analysis was performed on an ad hoc basis in response to NPOP consults and/or MTB cases.
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Using the same unique gene variants annotated by NoO and WfG, we queried all variants using the OncoKB curated database for the current study (Data Supplement). The public database21 includes information on the clinical actionability for each somatic gene variant organized by indication and four-tier levels of evidence (Tables 1 and 2) which are ultimately incorporated into cBioPortal22 for Cancer Genomics to aid physicians and cancer researchers.6 Many genes involved in tumorigenesis are not targetable with currently available drugs. More than 90% of alterations in OncoKB have biologic effects and are classified as oncogenic but not actionable. For actionability, tumor ontology is considered. OncoKB contains 43 tumor types with biomarker-drug associations and uses an open-source ontology, OncoTree,23 which was developed at MSKCC (699 tumor types). The Clinical Genomics Annotation Committee (CGAC) reviews the OncoKB alteration across 22 disease management teams. Curation reviews occur every 3 months, and CGAC recommendations and feedback are updated in real time.6
For this study, levels of evidence 2A and 2B were consolidated to level 2 and levels 3A and 3B to level 3 for both WfG and OncoKB. For actionability annotation comparisons, we mapped ontology from WfG to OncoKB to ensure that gene variants were properly annotated with their respective tumor type. In addition, for actionability annotation comparisons, we excluded microsatellite instability (MSI), as the MSI status was not entered into WfG and we do not have MSI information from WfG.
Among 1,227 NGS results, 1,388 unique variants were observed in 117 genes. The entire set of unique gene variants is shown in the Data Supplement. The genes with the largest number of variants included were: TP53 (270), STK11 (92), CDKN2A (81), ATM (67), PTEN (52), NF1 (46), and BRCA2 (45). The most common cancer was lung adenocarcinoma in 35.86% (440). Other cancer types included colon adenocarcinoma 9.21% (113) and lung squamous cell carcinoma 9.05% (111). The complete list of cancer types is shown in Figure 1.
Of the 1,388 unique gene variants, 1,082 were identified only by PGDx (a larger proportion of the samples were sequenced by PGDx), and 480 were identified only by Personalis, whereas 174 gene variants were generated by both vendors in different specimens. NoO classification should be similar for both vendors. The unique gene variants generated by each vendor are shown in the Data Supplement. The genes included in the gene panels are listed in the Data Supplement. We also list the well-characterized genes of each panel as well as the genes for which copy analysis is performed. For panel distribution by NGS samples, see the Data Supplement. All unique gene variants were annotated by NoO, WfG, and OncoKB. Out of the 1,388 unique gene variants, 337 (24.2%) were variants of unknown significance by OncoKB. Out of the 1,388 unique gene variants, 270 (19.4%) were variants of unknown significance by WfG.
For pathogenicity annotation, (ie, pathogenic and likely pathogenic variants v all other variants), there was fair agreement between WfG and OncoKB (76%; kappa, 0.22) and no agreement between WfG and NoO (30%; kappa, −0.26) as well as NoO and OncoKB (42%; kappa, −0.07; Table 3; Fig 2; Appendix Fig A1).
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There were 91 unique gene variant–diagnosis combinations identified as having level 1 drug actionability recommendations identified by WfG, OncoKB, or both (not available from NoO). As part of actionability annotation, we mapped diagnosis ontology from WfG to OncoKB for each observed diagnosis (Data Supplement).
There was moderate agreement between WfG and OncoKB (96.9%; kappa, 0.445), with 58 variants identified only by WfG as level 1 and 6 variants identified only by OncoKB as level 1 (Table 4). The complete set of level 1 drug recommendations for WfG and OncoKB are shown in the Data Supplement. When both annotation services had level 1 drug actionability, the recommended drugs were overwhelmingly identical. An example of a unique gene variant with drug actionability concordance is the exon 19 deletion in lung adenocarcinoma, EGFR-L747_S752del, with level 1 evidence for use of erlotinib, afatinib, or gefitinib using both WfG and OncoKB annotation services. Response rates of tumors with EGFR exon 19 deletions at L747 have been reported as high as 83.3%.24
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Among the 33 unique gene variant diagnoses identified as level 1 by OncoKB, WfG classification was level 1 in 27; for the 6 cases with discordant classification in WfG, 5 cases were lung adenocarcinoma EGFR mutations and a melanoma BRAF-V600R mutation. For the BRAF-V600R mutation in melanoma, WfG had no level 1 recommendations, whereas OncoKB had 5 drug or drug combinations as level 1. BRAF-V600R mutations constitute approximately 3%-7% of all BRAF mutations and were not included in the original BRAF/MEK inhibitors clinical trials.25 Although V600R is not listed on the BRAF/MEK FDA label, National Comprehensive Cancer Network panel guidelines from as early as 2016 consider single-agent BRAF inhibitor monotherapy and BRAF/MEK inhibitor combination therapy an appropriate treatment of all activating BRAF mutations, including V600R, V600D, and others.26 For EGFR mutations in lung adenocarcinoma (EGFR-A750P, EGFR-E746_T751delinsI, EFGR-G719C, EGFR-L861Q, and EGFR-S7681), WfG had no recommendations in 3 variants and had level 2A for EGFR-G719C and level 3B for both EGFR-A740P and EGFR L861Q for drugs afatinib, erlotinib, and gefitinib. For EGFR-L861Q, an uncommon EGFR mutation, the afatinib FDA label expanded to include EGFR-L861Q in January of 2018, which was after our annotation analysis. These approvals were based on findings from the phase 2 LUX-Lung 2 trial as well as the phase 3 LUX-Lung3 and LUX-Lung 6 trials that showed an objective response rate of 66% (95% CI, 47% to 81%).27
Among the 85 unique gene variant diagnoses identified as level 1 by WfG, OncoKB classification was level 1 in 27, and 58 had discordant classification. Most of the gene variant diagnoses (40/58 [68.9%]) with discordant recommendations were mismatch repair (MMR) genes, such as MLH1, MSH2, MSH6, and PMS2. The remaining gene variant diagnoses (18/58; 31.0%) with discordant recommendations included genes CDK4, EGFR, FGFR1, FLT4, KIT, PDGFRA, PIK3CA, POLE, PTEN, TSC1, TSC2, VEGFA, and VHL. For a lung adenocarcinoma case with MLH1-A42, which is part of DNA MMR genes and known to have increased MSI, WfG provide a level 1 recommendation for atezolizumab, nivolumab, and pembrolizumab. Although MMR status predicts the clinical benefit of immune checkpoint blockade in multiple tumor types,28,29 none of these drugs are FDA approved for MLH1 mutants. Similarly, for other MMR gene variants, WfG provided level 1 recommendations in the absence of an FDA on-label indication.
Precision medicine has promoted the development of biomarker-driven treatment strategies. There has been a surge in the genetic testing market, with a 10% annual increase in new genetic tests and a 20% annual increase in gene-based diagnostic tests.15,30 NGS generates massive amounts of data, and different biologic questions require the development of specific bioinformatics pipelines, which are frequently platform specific.30,31 The processing of raw sequence data has a profound effect on patient care and outcomes, and NGS test validation is necessary.32 Until recently, there were no established uniform technical standards for reporting tumor-derived NGS gene panel sequencing results.33 In this analysis, we examine a large number of clinically observed unique gene variants and compare annotations for pathogenicity and actionability through two commercial services, NoO and WfG, as well as an open database, OncoKB.
In efforts to establish guidelines for NGS gene panel interpretation of somatic variants, the Association of Molecular Pathology (AMP) and College of American Pathologists (CAP) issued a joint consensus of classification (Table 5).32,33 The four-tier system has different nomenclature and classification as compared with WfG and OncoKB (Tables 1 and 2). The WfG and OncoKB levels of evidence are similar and compatible, but not identical, to the AMP/CAP/ASCO evidence levels. The OncoKB evidence levels were mapped to the evidence levels for AMP/CAP/ASCO tier I and II variants (Table 5).34 We used the WfG and OncoKB classification systems to compare their levels to each other, and we found that variants classified as pathogenic had a wide range of concordance, from 30% to 76% (Fig 2; Table 3; Appendix Fig A1). In routine clinical practice, only gene variants that are pathogenic or likely pathogenic are considered for actionability, so misclassification in pathogenicity could readily affect provider prescribing. For drug actionability, there was moderate-strength agreement 96.9% (kappa, 0.445) for levels 1. In practice, levels of evidence 1 and 2A both frequently result in use of a targeted drug, so concordance in level 2A may be similar to level 1, and their combination may Boost concordance among annotation services for actionability. However, we expect greater discordance among levels of evidence 2B to 4.
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Although no direct comparisons between NoO, WfG, and OncoKB have been previously performed, WfG has been compared with MTBs.3 The utility of WfG was compared with MTBs by examining 1,018 cases analyzed by the University of North Carolina’s Human-MTB. WfG identified an additional 8 actionable genes (7 of which passed actionability criteria by Human-MTB). Mutations in these 8 genes were identified in 231 and 96 patients out of 703 and 315 patients with already identified actionable and no actionable mutations, respectively.3 Of the 7 actionable genes identified by WfG, 3 had no clinical trial available, and 4 were made potentially eligible for a biomarker-selected clinical trial. The reason for the added genes by WfG was believed to be the opening of several clinical trials within weeks of the WfG analysis. Most genes identified and reclassified as actionable, however, have yet to demonstrate their utility as predictive biomarkers of response to the recommended therapy. These actionable mutations identified by WfG were found retrospectively in 323 patients, of whom only 47 (4.6%) had active disease requiring further therapy. Moreover, none of the patients had treatment altered based on WfG’s recommendation. Cognitive computing may supplement MTBs, and multiple studies have shown concordance of > 90%.35,36 WfG may provide additional decision support in the current era of rapid generation of information from clinical trials.
Currently, existing evidence does not support population-based universal tumor sequencing.37 The SHIVA trial (ClinicalTrials.gov identifier: NCT01771458) examined patients with any metastatic solid tumor refractory to standard treatment and randomly assigned 195 to receive treatment on the basis of molecular profile (n = 99) versus standard treatment (n = 95). Median progression-free survival was 2.3 months (95% CI, 1.7 to 3.8 months) in the experimental group versus 2.0 months (95% CI, 1.8 to 2.1 months) in the control group (hazard ratio, 0.88; 95% CI, 0.65 to 1.19; P = .41). The study used a variety of tumor types and histologies with single molecular alterations as a predictor for efficacy of targeted agents in heavily pretreated patients, possibly reducing their effectiveness. Nevertheless, there were no differences in progression-free survival or overall survival, and off-label use of targeted agents was discouraged.38 The benefit of off-label use of molecularly targeted agents is largely debated in oncology; however, most agree that clinical trial enrollment should be encouraged to identify predictive druggable biomarkers.
Other prospective studies, including EXACT,39 MOSCATO-01 (ClinicalTrials.gov identifier: NCT01566019),40,41 and MD Anderson’s Phase I Clinic42,43 have shown promising results for targeted therapy on previously treated solid tumors. Additional studies examining the efficacy of off-label use of targeted therapy on the basis of NGS test results are underway: ASCO’s Targeted Agent and Profiling Utilization Registry (TAPUR) study (ClinicalTrials.gov identifier: NCT02693535),44 NCI-MATCH (Molecular Analysis for Therapy Choice) trial (ClinicalTrials.gov identifier: NCT02465060),45 and Pediatric MATCH (ClinicalTrials.gov identifier: NCT03155620). Results from NCI-MATCH for patients with PIK3CA mutations treated with taselisib show 0% objective response rate,46 whereas patients with FGFR pathway mutations treated with AZD4547 showed a 5% objective response rate.47 Currently, there are no randomized controlled trial results supporting a universal NGS-based treatment paradigm. Despite this, NGS testing continues to be incorporated into the clinic.48 In a accurate survey of 1,281 US oncologists, 75.6% reported using NGS tests to guide treatment decisions. Of these, 34% used them for patients with advanced refractory disease, and 17.5% used them for decisions on off-label use of FDA-approved drugs.49 More than 50% reported that NGS tests were difficult to interpret either often or sometimes, which is a separate but related challenge facing personalized medicine.49 The use of NGS will likely continue to grow, with providers facing uncertainty as to how to integrate its use into the clinic. Studies like ours are critical and further highlight the current shortcomings in precisely interpreting results of NGS gene panels for use in clinical management.
This work was conducted as a clinical operational analysis of the National Oncology Program Office, Office of Specialty Care Services, Department of Veterans Affairs. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. Presented at the ASCO Annual Meeting, Chicago, IL, June 1-5, 2018.
Supported by the Department of Veterans Affairs, Office of Specialty Care Services.
Conception and design: Evangelia Katsoulakis, Michael J. Kelley
Provision of study material or patients: Bradley Hintze
Collection and assembly of data: Evangelia Katsoulakis, Jill E. Duffy, Bradley Hintze
Data analysis and interpretation: Evangelia Katsoulakis, Bradley Hintze, Neil L. Spector, Michael J. Kelley
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Evangelia Katsoulakis
Stock and Other Ownership Interests: AbbVie, Alexion Pharmaceuticals, Biogen
Research Funding: Advantagene (Inst)
Neil L. Spector
Stock and Other Ownership Interests: Eydis Bio, Bessor Pharma
Research Funding: Immunolight
Patents, Royalties, Other Intellectual Property: I am on a patent related to my work with the company Immunolight; Patent through Eydis Bio
Michael J. Kelley
Consulting or Advisory Role: AstraZeneca, Eisai, IBM Japan
Research Funding: Bavarian Nordic, Novartis, AstraZeneca, Bristol-Myers Squibb
Other Relationship: IBM
No other potential conflicts of interest were reported.
Veterans Affairs National Precision Oncology Program.
National Precision Oncology Program (NPOP) services are available to all Veterans Affairs (VA) facilities and as of June 2018, over 72 different VA facilities submitted tumor samples. Following sequencing, a formal report of identified genomic aberrations is collated, annotated and included in patient records. The turnaround time is 14 days. NPOP provides a molecular oncology consultation service to assist VA clinicians with treatment decisions, and a case-based education-focused molecular tumor board. The users of NPOP are VA general oncologists and pathologists. Specialized oncologists and molecular pathologists oversee the program.
Panel information.
Panels were constructed to identify base/missense substitutions, insertions/deletions in protein-encoding regions, copy number variations, selected gene fusions/rearrangements and microsatellite instability (only on CancerSELECT 125 panel). There was overlap between the panels and a minimum of 500X DNA sequence coverage was required for all assays.
OncoKB pathogenicity and actionability.
Annotation of variant pathogenicity was executed using OncoKB support and through the API (http://oncokb.org/). Annotation of actionability as defined by the OncoKB Levels of Evidence was executed using OncoKB support and are available through the OncoKB annotator (https://github.com/). Data regarding all variants annotated as actionable per OncoKB at the time of the study are publicly available at https://github.com/.
Panel breakdown of the NGS samples.
The panel breakdown of the 1,227 NGS samples was: Personalis ACE CancerPlus (n = 404); Personal Genome Diagnostics (PGDx) CancerSELECT 125 (n = 286); PGDx CancerSELECT 203 (n = 75); PGDx CancerSELECT 88 (n = 176); PGDx CancerSELECT 64 (n = 1); PGDx unknown panel (n = 285).
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