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Novell eDirectory Design and Implementation : eDirectory 8.8
Novell Implementation approach
Killexams : Novell Implementation approach - BingNews https://killexams.com/pass4sure/exam-detail/050-895 Search results Killexams : Novell Implementation approach - BingNews https://killexams.com/pass4sure/exam-detail/050-895 https://killexams.com/exam_list/Novell Killexams : Novel Open RAN implementation guidance released
New guidelines on adopting an Open Radio Access Network architecture have been released by the Cybersecurity and Infrastructure Security Agency and the National Security Agency, SecurityWeek reports. Aside from facilitating increased interoperability, virtualization, artificial intelligence-enabled intelligence, cloudification, and innovation, Open RAN also presents new security issues for mobile network operators, according to the general-purpose document. "By nature, an open ecosystem that involves a disaggregated multi-vendor environment requires specific focus on changes to the threat surface area at the interfaces between technologies integrated via the architecture," said CISA and the NSA. MNOs have also been urged by the federal agencies to deal with security issues stemming from vendor components and open source software utilization. The document has also recommended addressing distributed denial-of-service attacks and other cloud infrastructure concerns pertaining to Open RAN. "As standards are developed and adopted by equipment manufacturers, software developers, integrators, and mobile network operators, these security considerations may be mitigated through the adoption of standards and industry best practices," said the document.
Mon, 19 Sep 2022 18:34:00 -0500 en text/html https://www.scmagazine.com/brief/vulnerability-management/novel-open-ran-implementation-guidance-released
Killexams : ANS professor featured in Center for Implementation’s monthly bulletin

Recently, a publication written by Dr. Julie Rutledge, Professor of Human Development and Family Science and Director of the ENRICH Center, was featured in the September issue of Implementation in Action, the Center for Implementation’s monthly bulletin. 

Rutledge, along with co-authors from the University of Arkansas for Medical Sciences, discussed how partner groups can sustain research programs in a peer review article titled, “Implementation attitudes, fidelity, and adaptations: A novel approach to classifying implementer behavior.” 

This peer review focused on a small-scale implementation trial was conducted in 38 early care and education classrooms that were part of the Together, We Inspire Smart Eating (WISE) program. This program focuses on four evidence-based practices that are implemented by teachers to promote nutrition, such as repeated hands-on exposure to target foods. 

Throughout the trial, objective measures such as classroom observations and subjective measures like self-report on attitude were used to determine how closely teachers implemented the program in the classroom compared to how they were trained, attitudes toward the program, and influence in their early care and education centers. The group called this a Fidelity, Attitude, and Influence Typology (FAIT).

Rutledge said determining their typology (FAIT) allows the research team to individualize the kind of support that is provided to meet the people who are implementing where they are and provide the help that may be needed to be successful doing the program and continue implementing it long-term. 

Applying this implementation typology can help to identify the barriers that may discourage the sustainability of a project which can bridge the gap between the real world and researchers. 

“The mission of this project, for us, is to understand how we can help teachers implement programs based on their response,” Rutledge said. “If there are barriers found within these categories then we can work to provide a different approach or new perspective to the implementation of the program. And, this typology system can be applied to numerous projects to help intervention researchers work collaboratively with community partners to increase the success of their programs.”

Thu, 13 Oct 2022 06:05:00 -0500 en-US text/html https://www.latech.edu/2022/10/13/ans-professor-featured-in-center-for-implementations-monthly-bulletin/
Killexams : Beyond traditional remedies: A novel anti-inflationary approach

When I was a student of economics, Keynesian economics was the coin of the realm. I saw it as somewhat of the holy grail largely because it offered a logical framework with which to view the world, enabling one to devise straight-forward solutions to profoundly significant problems. The Keynesian remedy to address inflation, for example, is simple: contractionary economic policies — both fiscal and monetary. These policies are designed to curb spending and thereby lessen the pressure for pushing prices higher. Viola! Problem solved.

On the fiscal side, contractionary policy means reducing government spending, increasing taxes, or some combination of the two. Lower government spending directly dampens aggregate demand by the government sector, which represents roughly two-fifths of the US economy. Higher taxes reduce spending by consumers and businesses, indirectly, by lowering disposable income. Tight monetary policy slows the growth of the money supply thereby ratcheting up interest rates and again tamping down consumer and business spending particularly by those for whom purchases are conditional upon borrowing money.

My reservation about these Keynesian anti-inflationary remedies is that they supply little or no consideration to the demographic considerations as to who bears the brunt of these economic policies. The divide between those whose income barely covers living expenses and those who operate with a larger financial cushion is stark. Under an inflationary regime, those at the bottom of the economic ladder are forced to do without for at least some critical purchases necessary for maintaining basic health and well-being. With the kind of inflation we’re experiencing, those who are better off can more easily accommodate to higher prices, at least for a time, without seriously impacting their quality of life. Keynesian economics has nothing to say about this dichotomy.

I’ve struggled with the question of what can be done to fight inflation without imposing this disproportionate burden on the most vulnerable of our society. I’m pleased to be able to report, however, that I’ve just read a piece authored by Ezra Klein, a podcaster and frequent op-ed contributor to the NY Times, that may well untie this Gordian knot for me. Klein is suggesting that a tax on consumption may be the way to go. The idea isn’t without its problems; but conceptually, I think Klein’s suggestion is worthy of consideration.

Some definitional foundation is needed: Income is money that is earned over some span of time, and it gets divided between consumption and saving. Mathematically, Income = Consumption + Saving.

In this context, consumption includes any purchases of non-financial goods or services, including the purchases of real assets such as real estate, commodities, art, etc. Saving, on the other hand, is comprised of purchases of financial assets including additions to savings accounts and money market deposits — i.e., any income not spent on consumption.

The rationale for a consumption tax is straight forward. If we want to disincentivize spending on those items that impact inflation, we should do so by making consumption more expensive. Put another way, we shouldn’t tax saving. In his latest opinion piece in the Times, Klein points out that those in the top quintile by income are responsible for 40 percent of aggregate consumption expenditures, while the bottom quintile contributes only 10 percent of that total. Thus, if we want to impose the tax where it would have its greatest effect on consumption, we should concentrate the effort with higher income households.

To that end, Klein calls for a progressive tax to consumption (i.e., higher tax rates for higher levels of consumption), with a “hefty” standard deduction. I’m relying on Klein’s research here, but he credits Cornell Professor Robert Frank who had written about instituting a progressive consumption tax as early as 2005, for the genesis of this idea.

I’m especially impressed by Klein’s suggestion of using the consumption tax as an automatic stabilizer, whereby it would work as an adjunct to our current income tax structure. Consumption taxes could be phased in and out as inflation surpasses or recedes from some prescribed critical level. In this way, consumption taxes would play an incremental role in fighting inflation, as opposed to being the primary source of funding government expenditures. But, again, the tax on consumption is an anti-inflationary tactic that is sensitive to the idea of equity.

A number of practical considerations would have to be worked out, but none are all that different from those that had to be settled in connection with our current income tax regulations. First, the measure of consumption used as the basis for the consumption tax would likely be derived residually. That is, we would first determine income and then subtract from that value any new acquisitions of financial assets.

The determination of income, however, is itself problematic. Taxable income for income tax purposes excludes a host of exclusions and deductions. It’s not clear that those same deductions and exemptions should apply in the calculation of consumption relevant to the determination of a consumption tax; but whatever the formula enacted for calculating income and consumption for this purpose, we’d want to make one critical carveout. Assuming we include realized gains or losses from the sale of any financial asset in the calculation of income in the general case, because our intent is to tax consumption, per se, we’d want to exempt income from the sale of a financial asset when the proceeds of that sale are reinvested into a different financial asset. That is, capital gains or losses would affect this income measure if and when the proceeds from the sale were used to buy goods or services; but otherwise, if those proceeds were rolled over into a new financial asset position, the realized gains or losses would not be included in income, thereby leaving consumption unaffected by the substitution.

I’m envisioning three basic criticisms about the implementation of the consumption tax: (1) The idea of taxing something that can’t be readily and directly measured may foster a lack of consistency in the way the consumption taxes would be calculated across taxpayers. (2) The timing of when these taxes would be paid matters. With annual payments, it’s not clear that taxpayers will plan ahead and respond as we might like to the intended spending disincentives. And (3) taxes are already too high. Our fiscal effort to combat inflation should rely exclusively on cutting government spending, and we shouldn’t increase taxes at all.

My response to each: (1) It’s hard to supply all that much credence to the concern that this particular calculation for consumption is too complicated or difficult for the public to understand. It’s certainly no more difficult that the rules and regulations that pertain to the current practice of collecting income taxes. (2) The concern about timing is legitimate. It would be ideal to have any consumption tax collected on a concurrent basis, but that would be next to impossible. Whether this deficiency should be overriding, however, is another issue. I would hope that with the aid of public service announcements, the support of the community of tax preparers, and perhaps some adjustability built into the way we assess payroll taxes and estimated income tax requirements, we may be able to mitigate some portion of this problem. (3) My expectation is that of the three concerns listed, the resistance to any higher taxes is probably the most significant impediment to the implementation of a consumption tax.

I find it ironic that, often, those with the shrillest voices demanding fiscal action to tame inflation are the same voices that argue most vociferously against raising taxes. Most disturbing to me is that theirs is an extreme position allowing for no compromise. Any tax increase is too big, irrespective of their purported concern about the level of inflation. That posture makes no sense to me. Perhaps even more disturbing than that, the insistence to resist any compromise or accommodation with “the other side” is emblematic of the worst of America today. I wish it weren’t so. Institution of some form of a consumption tax seems to me to be worth a try.

Mon, 03 Oct 2022 06:42:00 -0500 en text/html https://www.fxstreet.com/analysis/beyond-traditional-remedies-a-novel-anti-inflationary-approach-202210031842
Killexams : Novel Approach Developed for Ear Replacement Surgery

Credit: Pixabay

In a recent study published in Facial Plastic Surgery & Aesthetic Medicine, a team of researchers have developed a new method for ear replacement surgery, which is traditionally quite difficult using a patient’s rib cartilage. This study has the potential to produce simpler, faster, and more accurate ear replacement surgeries, and was conducted by researchers from the United States.

There are two types of congenital ear malformations that newborns exhibit: anotia (total absence of an ear) and microtia (just a cartilage stump of an ear), and it is estimated by the National Birth Defects Prevention Network that one in every 8,000 to 10,000 births are exhibit one of these two malformations.

As stated, this type of ear replacement surgery is traditionally difficult. Now, because of two novel tools developed by Dr. Angelo Leto Barone, who is a craniofacial and pediatric plastic surgeon at Nemours Children's Health in Orlando, Florida, and former resident of plastic and reconstructive surgery at the Johns Hopkins University School of Medicine, this type of surgery could soon be done simpler, faster, more accurate, and will be able to “custom fit” the new organ for every patient.

"Although ear reconstruction surgery for repairing microtia and anotia in both pediatric and adult cases has been practiced for a number of years, it still is a demanding procedure for both the patient and the surgeon," said Leto Barone. "What makes it really difficult is that to construct a suitable ear requires a bit of artistic skill."

For the study, Leto Barone and his colleague, Dr. Anirudh Arun, who is a Johns Hopkins interventional and diagnostic radiology surgery resident, 3D printed two assistive devices, therefore requiring less innate talent to perform the surgery. The first tool is an easy-to-use carving tool designed to precisely slice a patient’s rib cartilage to any desirable thickness while reducing waste. The second tool is described as a “cookie-cutter-like” press that uses steel blades that are shaped in designs fabricated from the patient’s normal ear and come together during surgery to form the new ear.

"The cartilage-slicing device basically doubles the amount of cartilage tissue available for surgery, meaning that less has to be harvested to safely produce the entire ear," said Arun. "We only need two and a half ribs instead of the traditional four from prior techniques -- less waste and less discomfort for the patient."

After the cartilage slices are placed into the second cutter, they are trimmed exactly into the pieces of the new ear within minutes rather than the traditional hours-long manual work with a scalpel.

"Not only is the process quicker, but the template eliminates the cartilage damage that often accompanies the sculpting done in previous reconstruction methods," said Leto Barone. "This makes our system highly reproducible, user friendly, time efficient and cost effective. Best of all, it consistently yields a natural-looking ear that helps children avoid being teased or bullied and enables adults to do things others take for granted, like wearing glasses."

Sources: Facial Plastic Surgery & Aesthetic Medicine

As always, keep doing science & keep looking up!

Thu, 22 Sep 2022 22:00:00 -0500 text/html https://www.labroots.com/trending/health-and-medicine/23630/novel-approach-developed-ear-replacement-surgery-2
Killexams : Comic Contracts: A Novel Approach To Contract Clarity And Accessibility

Credit: Fruit Picker contract pages by Jincom

Beware the fine print is the oft-repeated expression heard in almost any deal or contract negotiation. It’s good advice that too often is ignored in daily life and job situations—especially among those segments of the population that may not have excellent English language skills, or for that matter, anyone without experience with the often-impenetrable legalese featured in contracts.

Until now.

Robert de Rooy is an attorney based in South Africa and the founder of Comic Contracts -- and this is no joke.

Comic contracts are documents that are:

• Legally binding contracts in which parties are represented by characters

• The agreement is captured in pictures

• The parties sign the comic as the contract

“We produce illustrated contracts for people who are illiterate, people who are not literate in the language of the contract, employers with multi-cultural workplaces or companies that wish to transact with people who suffer from reading or intellectual disabilities. We want to enable people to be able to independently understand the contracts they are expected to sign.”

Those who are fans of contracts that have transparency, visibility, simplicity and clarity should take note.

De Rooy laid out the comic contract idea in a latest presentation at an International Association for Contract and Commercial Management (IACCM) Americas Conference. He says the comic contract was inspired by, and builds on, the work of preventative law and proactive contracting—a “movement in law that is being led by Professors Tom Barton (USA) and Helena Haapio (Finland), which promotes the use of visualization as a non-binding aid in understanding the text of an agreement, and thereby creates more ‘fit for purpose’ contracts designed for better relationships and better outcomes.”

Optimizing contract outcomes is the goal, no matter who the parties are, or their situation. Or, as de Rooy puts it: “We want contracts to be useful in aligning expectations and to signal healthy relationships towards successful outcomes. We don’t try to serve the interests of any party, we try to serve the relationships between them.”

Beyond Text-based Contracts: Examples Of Comic Contracts In Practice

Comic contracts step out of the “text”-based contract paradigm, de Rooy explains. Pictures can are not only useful to aid understanding of the text in a contract, pictures can actually “be” the contract.

This takes contracting to a new and exciting level by making the contract document accessible to everyone. This offers a proactive and workable solution to the challenge faced by vulnerable or illiterate people when they are expected to sign, and be legally bound by, text agreements that they are not able to understand.

De Rooy explained the genesis of comic contract. He had been working on the idea for some years, and entered a description of the idea into a legal innovation competition in 2014, but it received no notice. A kind introduction by Kim Wright, an American lawyer and the American Bar Association’s Legal Rebel in 2009, to Professor Haapio, led to an invitation to present the idea at the Contract Simplification Conference in Switzerland in May 2016. “I could describe the idea, the theory of it and had some samples of illustrated clauses but I still did not have a complete field and signature ready agreement. This is where one of my practice’s clients stepped up to the plate. Indigo Fruit Farming gave me some budget to work with a Cape Town company called Jincom to produce a complete and professional quality Fruit-picker contract for their citrus farms.”

So, when he presented his idea, this time, he had something to show: “I did not have to try to describe the idea, the audience could see it, and they loved it. Moreover, I could tell them that this contract was actually going to be implemented.”

Initially, de Rooy was “worried that the workers would perceive the contract as patronizing, and the farm managers were concerned about doing things differently. So, it was agreed that their comic contract would first be presented to a group of workers they knew are unlikely to cause a problem if they did not like it for any reason. When this went well, it was then presented to a general group of new workers.”

After the contracts were signed, and the feedback came from the workers, “Indigo felt so proud that they wanted their consumer brand “Clemengold™” brand displayed on the contract.”

Robert has now partnered with Jincom to produce comic contracts for other companies who like this idea and want it for their people.

Apart from the Fruit-Picker agreement, other examples of comic contracts that have been or are being developed, include:

• A Generic Farm Laborer contract for the South African Wine and Agricultural Ethical Trading Association (WIETA), a multi-stakeholder, non-profit voluntary organization, which promotes ethical trade in the wine industry value chain. Stakeholders include producers, retailers, trade unions, non-governmental organizations and the government.

• Shop-floor Worker contract for a dairy business

• Kitchen Staff contract for a hotel group

• Codes of Conduct for sport clubs in Australia

• Domestic worker contracts

• Loan agreements

• Funeral Insurance contracts

• Rental contracts

We Are Defined By Our Ability To Understand Contracts

De Rooy observes that the law uses “a blunt instrument called age, and assumes that when you reached the age of 18, you can read and understand contracts. If you sign an agreement after age 17, it’s not binding without your parent’s signature. But when you sign it after age 18, it’s binding. “When one is well-educated, that's reasonable, but if you are vulnerable, illiterate or simply faced with a contract that is not in your native language, you are factually in the same position as a small child, except that the law offers you no protection.”

Tim Cummins, IACCM CEO, provides insight into the use of comic contracts. “Our long-held perspective is that today's contract design and structure is frequently a source of risk. Contracts contain important information that the typical user finds hard to understand, a belief confirmed by latest IACCM research where 88% of business people said that 'contracts are difficult or impossible to understand'.

“We have supported new thinking in contract design for several years, introducing a design award in 2012. Therefore, we were delighted to discover the exciting innovation by Robert -- a remarkable example of social responsibility, inclusive thinking and effective risk management that has led to better economic results for both employer and workers. We continue to encourage new thinking and we are delighted by the steady recognition in major corporations that this is a path they should follow.”

Cummins noted IACCM members were so impressed with the comic contract concept that de Rooy was selected to receive the “Program of Visionary Change Award” at the organization’s Americas conference last year. He noted IACCM members were so impressed with the comic contract concept that de Rooy was selected to receive the “Program of Visionary Change Award” at the organization’s Americas conference last year.

Using comics as the contract might sound condescending, especially with respect to illiterate people. That is not the intent; it’s reality that illiterate people should sign contracts they understand. The purpose is to fill a serious need and a void in the ‘art’ of contracting.

Tue, 11 Oct 2022 05:14:00 -0500 Kate Vitasek en text/html https://www.forbes.com/sites/katevitasek/2017/02/14/comic-contracts-a-novel-approach-to-contract-clarity-and-accessibility/
Killexams : Novel physical therapy approach improves recovery

MIRAMAR, Fla. – Each year, half of all Americans over the age of 18 will develop an injury that lasts longer than three months and often requires physical therapy.

At Memorial Healthcare outpatient rehabilitation centers, therapists are now working with a novel approach that’s helping patients gain strength without lifting heavy loads.

One such patient is 16-year-old Marcus Arayata, who’s passionate about playing soccer.

During practice in early 2022, a simple move caused severe damage to his knee.

“I didn’t think much of it until I got my MRI where they said I completely tore it, and it was like, ‘Oh, this is big news’ because it was nothing I really expected,” Arayata said.

Following surgery to repair the injury, he began physical therapy at Joe DiMaggio Children’s Hospital Rehab at Memorial Miramar where specialists are working with an innovative approach called Blood Flow Restriction Training.

“The idea of it is you’re taking a person’s leg or their arm and you’re putting a cuff on their arm, and you’re basically restricting the flow of blood to that body part,” said Davide Ioffredi, a licensed physical therapist and athletic trainer with Joe DiMaggio Children’s Hospital.

By restricting blood flow, and, in turn, oxygen, the process actually creates a high level of strengthening without the need for heavy weight-bearing exercises.

“The concept is you’re doing a very basic exercise, such as lifting your leg, and it creates an effect that your muscles feel like they’re lifting 1,000 pounds or 2,000 pounds,” Ioffredi said.

In the end, patients can recover more quickly from injury.

“You’re kind of startling the body and it creates this response where hormones are being released and you get a lot more strengthening,” Ioffredi said.

Though he was skeptical at first, Arayata said the results speak for themselves.

“My goal is by the end of the year to at least play a game, which I’m really looking forward to,” he said.

Blood Flow Restriction Training is regulated and based on specific parameters to make it safe for the patient.

Copyright 2022 by WPLG Local10.com - All rights reserved.

Fri, 23 Sep 2022 03:18:00 -0500 en text/html https://www.local10.com/health/2022/09/23/novel-physical-therapy-approach-improves-recovery/
Killexams : Novel Approaches to Assess Hypertension Control Outside the Office

Within the last 24 months, I have financial relationship(s) or affiliation(s) with a manufacturer, marketer, reseller, or distributor of a healthcare product or service involved in the management of patients with any cardiovascular disease to include devices, drugs, and digital health care products listed below:

  • Consultant Fee/Honoraria/Speaker's Bureau (Personal) - Medtronic; Recor Medical; Aktiia
  • Grant Support/Research Contract (Institutional) - Recor Medical; Aktiia
Sat, 17 Sep 2022 01:50:00 -0500 en text/html https://www.tctmd.com/slide/novel-approaches-assess-hypertension-control-outside-office
Killexams : Labskin to develop new revolutionary approach to testing for radiation exposure

Labskin is delighted to announce our selection by The Intelligence Advanced Research Projects Activity (IARPA), part of the US Office of the Director of National Intelligence, to join a team of experts to develop new ways to evaluate radiation exposure in civilians and military personnel.

Labskin to develop new revolutionary approach to testing for radiation exposure

Image Credit: Labskin

Labskin is a key member of a consortium selected to develop these technologies in collaboration with a multidisciplinary team of experts including professors from the University of Columbia in New York, Georgetown University in Washington DC, the Georgia Institute of Technology, scientists from the American Type Culture Collection (ATCC) and computer scientists and researchers from the project lead ARETE Associates, a Defense contractor specializing in sensing solution and machine learning algorithms.

In a project worth $800k, starting immediately, Labskin will help develop this technology into minimally invasive testing for radiation for a program known as Targeted Evaluation of Ionizing Radiation Exposure (TEI-REX). TEI-REX aims to develop novel approaches to evaluate organisms exposed to low-dose ionizing radiation. Labskin coupled with Skin Trust Club’s expertise in skin research and microbiology is essential for the project.

The goal of the project is to develop a new biodosimetry standard which could be applied to maintain the safety of military and civilian populations working or living in close proximity to ionizing radiation sources, such as: nuclear plants, nuclear vessels, ammunition, etc. Labskin’s contribution is the creation of a simple non-invasive swab test to collect signatures from the skin surface that allows machine learning algorithms to detect and quantify the impact of any amount of radiation exposure on the skin microbiome.

This is an unique opportunity to revolutionize the way we test for radiation exposure. Labskin and Skin Trust Club are at the forefront of an increasing number of cutting edge technologies that are changing our world. This technique can also be applied to detect the impact of pollution or a variety of chemicals on the environment. Furthermore, this type of testing could not only be used to detect exposure to these kind of events in humans but also in complex ecological systems such as the soil, crops or sediments”

David Caballero-Lima, Chief Scientist, Labskin

We are committed to the success of this very exciting project. The inclusion of Artificial Intelligence and the opportunity to work with ARETE Associates, with their vast experience in complex AI applications, will result in further advances in how AI can be used in conjunction with our skin model at scale. This project coincides with completion of the expansion of our US labs in Delaware, which will greatly help the implementation of this large project. We believe our proven ability to transition technology to the field with Skin Trust Club will be invaluable as we progress this project.”

Colin O’Sullivan, Chief Information Officer, Labskin

Thu, 06 Oct 2022 00:09:00 -0500 en text/html https://www.news-medical.net/news/20221006/Labskin-to-develop-new-revolutionary-approach-to-testing-for-radiation-exposure.aspx
Killexams : A potentially novel approach to improving the efficacy of natural killer cell therapies

Natural killer (NK) cells have lately become a hot focus of efforts to develop new immunotherapies. Researchers led by Ludwig Harvard's Tony Letai, whose team collaborated closely with the Ludwig Harvard Kai Wucherpfennig lab in this study, reported in an April issue of Cell a potentially novel approach to improving the efficacy of NK cell therapies.

The new strategy described by Letai and his team builds on their discovery that NK cell-induced apoptosis of cancer occurs through a that involves the mitochondria. This mechanism—"mtApoptosis"— depends on the balance of pro-apoptotic and anti-apoptotic proteins in the mitochondrion. Whether a cell destroys itself depends on which way that balance is tipped. The researchers showed that targeting by NK cells tips the balance in favor of pro-apoptotic proteins and so primes cancer cells for mtApoptosis.

Combining NK cells with a class of drugs—BH3 mimetics—that push the balance further in that direction led to the synergistic killing of cancer cells in culture and the suppression of tumor growth in mouse models of cancer. They also show that a method for screening drugs developed in Letai's lab, BH3 profiling, can be used to identify the BH3 mimetic drug most likely to augment NK cell killing of a given cancer.



More information: Rongqing Pan et al, Augmenting NK cell-based immunotherapy by targeting mitochondrial apoptosis, Cell (2022). DOI: 10.1016/j.cell.2022.03.030
Journal information: Cell

Citation: A potentially novel approach to improving the efficacy of natural killer cell therapies (2022, September 20) retrieved 17 October 2022 from https://medicalxpress.com/news/2022-09-potentially-approach-efficacy-natural-killer.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Tue, 20 Sep 2022 02:40:00 -0500 en text/html https://medicalxpress.com/news/2022-09-potentially-approach-efficacy-natural-killer.html
Killexams : Despite Exciting Newcomer Drugs, Uptake of HF Meds Still Meek Across Oceans

Even with the introduction of newer, better-tolerated medications, the slow and rocky implementation of guideline-directed medical therapies (GDMTs) for heart failure (HF) has remained a global issue, a study found.

Among Americans who were new users of any GDMT drug class after HF hospitalization, those initiating dapagliflozin (Farxiga) and sacubitril/valsartan (Entresto) had waited 33 and 19 days, respectively, in comparison with the 18-24 days for older GDMTs. The difference was similar in Japanese and Swedish registries, according to Gianluigi Savarese, MD, PhD, of Karolinska University Hospital in Stockholm, Sweden, and collaborators of the EVOLUTION HF study.

Moreover, the proportion of people initiating dapagliflozin or sacubitril/valsartan by day 30 after discharge reached 37.3% and 62.0% in the U.S., 74.6% and 72.7% in Japan, and 54.9% and 59.5% in Sweden, Savarese's group reported in a paper published in JACC: Heart Failure.

"Despite the paradigm-shifting trial results for novel GDMTs, early initiation of novel GDMTs in real-world settings remains a clinical challenge," the authors wrote. "However, SGLT2 inhibitors have entered clinical guidelines only recently, and changes in treatment strategies may Strengthen over time."

"These results show an urgent need for earlier use of novel GDMTs to Strengthen patient outcomes, particularly of dapagliflozin, which has been shown to reduce mortality in patients with HF," the team concluded.

Dapagliflozin was the only SGLT2 inhibitor considered in the study, which captured GDMT uptake starting from the first full calendar month after dapagliflozin's approval for HF across the three countries: Japan (December 2020), Sweden (December 2020), and the U.S. (June 2020).

SGLT2 inhibitor therapy has been shown to safely treat HF patients across the spectrum of ejection fraction and is associated with better ease of use, compared with other GDMTs, given its once-daily dosing and lack of need for titration.

Indeed, Savarese's team reported that when pooled across countries, the proportion of HF patients discontinuing dapagliflozin within 12 months was a relatively low 23.5%, with over three-quarters of people meeting their full target dose.

Rates of discontinuation and target dose misses were about the same or higher with sacubitril/valsartan and other GDMTs, namely angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists.

The present study is the latest of many reports to describe the poor uptake of GDMTs for HF. It may appear that the Japanese and the Swedes do a better job than the Americans, but the issues are apparent across these countries, commented Tariq Ahmad, MD, MPH, of Yale School of Medicine in New Haven, Connecticut.

"This is basically showing again that there is a huge lag between availability of data and its translation at the bedside," Ahmad said in an interview. "The majority of people are not practicing the best evidence-based medicine and are probably not reading these papers. We need a behavioral economics approach to why the gap seems to be bigger in heart failure than some other cardiology specialties."

He said he suspected the main barriers to better GDMT implementation are inertia, paperwork and cost, and lack of knowledge among the non-HF specialists, who treat the majority of HF patients. "There's a lack of consensus among the general medicine physicians on starting these medications. That is a big issue," he said.

At Yale, Ahmad's group was able to boost GDMT uptake using a clinical decision-support intervention in the PROMPT-HF trial. Outpatient clinicians were alerted every time they accessed the electronic health record of an HF outpatient not on one of four GDMT medication classes, and were given individualized guidance on prescribing GDMT. "The improvement was not dramatic," he acknowledged.

"While the discovery of novel therapies is exhilarating, we must spend an equal amount of attention and focus on understanding what the barriers are to getting patients on these medications and then direct our energies to mitigating those barriers," said Anu Lala, MD, of Mount Sinai Health System in New York City, who was not involved in EVOLUTION HF.

This observational cohort study had relied on Japan's Medical Data Vision claims registry, Sweden's nationwide administrative registries, and the U.S. Optum de-identified Market Clarity database.

Out of over three million people in those three countries, investigators identified 266,589 people initiating any GDMT drug class within 12 months of an HF hospitalization discharge who had sufficient data.

Across the board, patients initiating dapagliflozin or sacubitril/valsartan tended to be younger and less likely female than those starting other drug classes.

Savarese and colleagues warned, however, that their dataset lacked key information such as ejection fraction data.

"These data add to the growing body of evidence representing the need for implementation of our guideline-directed therapies that we know save lives and decrease hospitalizations," Lala maintained.

  • Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

EVOLUTION HF is funded by AstraZeneca.

Savarese disclosed grants from AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Merck, Novartis, Pharmacosmos, and Vifor; and personal fees from AstraZeneca, Cytokinetics, Medtronic, Pharmacosmos, Roche, Servier, and Vifor.

Ahmad reported research funding from AstraZeneca.

Lala disclosed serving on advisory boards for Merck and Bioventrix and receiving speaker honoraria from Zoll.

Fri, 14 Oct 2022 04:36:00 -0500 en text/html https://www.medpagetoday.com/cardiology/chf/101231
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