Category Archives: Molecular Medicine

Wilmington, Delaware, United States, Transparency Market Research Inc.: Eye-related disorders are expanding at an accelerated pace across the globe. One of the most common disorders of the eyes is dry eye disease. The growing geriatric population and the increasing screen time among individuals have resulted in the rising cases of dry eye diseases. According to numerous studies, the incidence of dry eye diseases is between the ranges of 8 percent to 34 percent. Hence, these factors have influenced the growth structure of the dry eye disease market considerably and will continue to influence during the forecast period of 2017-2025.

When an individual suffers from dry eye disease, his/her eyes do not produce enough tears. Dry eye also occurs when one is not able to maintain a normal layer of tears for coating the eyes. The common symptoms of dry eye disease are redness, stringy mucus, blurry vision, pain, difficulty reading, or not able to sit before the computer for long hours, etc. Dry eye disease is of two types: aqueous deficiency dry eye disease and evaporative dry eye disease.

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The prominent risk factors for eye diseases are diabetes, refractive surgeries, aging, consumption of certain medications, etc. Anti-inflammatory drugs, cyclosporine, artificial tears, lifitegrast, secretagogue, punctal plugs, and others are some vital treatment types for eye diseases.

The players indulge in research and development activities for expanding the growth landscape of the dry eye disease market. The players invest in these activities to find new treatments for dry eye diseases. These activities help in strengthening the revenue cycle of the global market, eventually increasing the growth rate. Mergers, acquisitions, joint ventures, and partnerships also form an important part of the dry eye disease market growth structure. These collaborations assure expansion of the treatment types in other regions and significantly impact the growth trajectory.

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According to the TMR experts, the market for dry eye disease is prognosticated to expand at 4.5 percent CAGR during the forecast period of 2017-2025. In the context of valuation, the plasma protein therapeutics market is estimated to reach a valuation of US$ 7,780 mn by 2025 and was valued at US$ 5045.2 mn in 2016.

Anti-Inflammatory Drugs to Reign Supreme in Terms of Demand

The use of anti-inflammatory drugs for treating dry eye diseases has increased exponentially over the years. Research activities revolving around anti-inflammatory drugs are increasing extensively, ultimately leading to an increase in the development of new drugs. These factors will influence the growth of the dry eye disease market to a considerable extent. The anti-inflammatory drugs segment is expected to dominate in terms of revenue and demand, whereas the artificial tears segment may emerge as the second-largest growth-contributing segment.

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Growing Awareness about Various Treatment Types to Increase Growth Prospects Considerably

Government and non-government initiatives are encouraging many individuals to diagnose and get treated for dry eye diseases. This factor will have a great impact on the growth of the dry eye disease market. Further, many companies in the dry eye disease market promote their products through effective strategies, ultimately contributing to the growth trajectory.

Accelerated FDA Approvals to Boost Growth of North Americas Dry Eye Disease Market

The approvals for new dry eye disease treatment drugs at a rapid pace will bring immense growth prospects for the dry eye disease market in North America. The Food and Drug Administration (FDA) is trying to speed up the approval process to provide good and effective dry eye disease treatment options to the citizens. Hence, this factor will help North Americas dry eye disease market to gain a larger growth share.

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Some well-entrenched players in the dry eye disease market are Sun Pharmaceutical Industries Ltd., Valeant Pharmaceuticals International, Inc., Otsuka Pharmaceutical Co., Ltd., TRB Chemedica International SA, Novartis AG, Johnson & Johnson, and Sentiss Pharma Pvt. Ltd.

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Dry Eye Disease Market: Increasing Awareness and the Booming Geriatric Population to Accelerate the Market Growth - BioSpace

image:For innate immune system activation against HIV-1, Scripps Research scientists have found that the protein PQBP1s recognition of incoming HIV-1 particles (depicted in red) is required for cGAS activation, a production of cGAMP (depicted in green), in human dendritic cells. Nuclei (Dapi) are depicted in blue. view more

Credit: Scripps Research

LA JOLLA, CA Human immunodeficiency virus 1, more commonly known as HIV-1, is known for its uncanny ability to evade the immune system. Scientists at Scripps Research and collaborators have now uncovered how our innate immune system the bodys first line of quick defense in attacking foreign invaders detects HIV-1, even when the virus is present in very small amounts.

The findings, published on July 8, 2022, in Molecular Cell, reveal the two-step molecular strategy that jolts the innate immune response into action when exposed to HIV-1. This discovery could impact drug development for HIV treatments and vaccines, as well as shape our understanding of how the innate immune response is implicated in other areas including neurodegenerative disorders such as Alzheimers.

This research delineates how the immune system can recognize a very cryptic virus, and then activate the downstream cascade that leads to immunological activation, says Sumit Chanda, PhD, professor in the Department of Immunology and Microbiology. From a therapeutic potential perspective, these findings open up new avenues for vaccines and adjuvants that mimic the immune response and offer additional solutions for preventing HIV infection.

The innate immune system is activated before the adaptive immune system, which is the bodys secondary line of defense that involves more specialized functions, such as generating antibodies. One of the innate immune systems primary responsibilities is recognizing between self (our own proteins and genetic material) and foreign elements (such as viruses or other pathogens). Cyclic GMP-AMP synthase (cGAS) is a key signaling protein in the innate immune system that senses DNA floating in a cell. If cGAS does detect a foreign presence, it activates a molecular pathway to fight off the invader.

However, because HIV-1 is an RNA virus, it produces very little DNA so little, in fact, that scientists have not understood how cGAS and the innate immune system are able to detect it and distinguish it from our own DNA.

Scripps Research scientists discovered that the innate immune system requires a two-step security check for it to activate against HIV-1. The first step involves an essential protein polyglutamine binding protein 1 (PQBP1) recognizing the HIV-1 outer shell as soon as it enters the cell and before it can replicate. PQBP1 then coats and decorates the virus, acting as an alert signal to summon cGAS. Once the viral shell begins to disassemble, cGAS activates additional immune-related pathways against the virus.

The researchers were initially surprised to find that two steps are required for innate immune activation against HIV-1, as most other DNA-encoding viruses only activate cGAS in one step. This is a similar concept to technologies that use two-factor authentication, such as requiring users to enter a password and then respond to a confirmation email.

This two-part mechanism also opens the door to vaccination approaches that can exploit the immune cascade that is initiated before the virus can start to replicate in the host cell, after PQBP1 has decorated the molecule.

While the adaptive immune system has been a main focus for HIV research and vaccine development, our discoveries clearly show the critical role the innate immune response plays in detecting the virus, says Sunnie Yoh, PhD, first author of the study and senior staff scientist in Chandas lab. In modulating the narrow window in this two-step process after PQBP1 has decorated the viral capsid, and before the virus is able to insert itself into the host genome and replicate there is the potential to develop novel adjuvanted vaccine strategies against HIV-1.

By shedding light on the workings of the innate immune system, these findings also illuminate how our bodies respond to other autoimmune or neurodegenerative inflammatory diseases. For example, PQBP1 has been shown to interact with tau the protein that becomes dysregulated in Alzheimers disease and activate the same inflammatory cGAS pathway. The researchers will continue to investigate how the innate immune system is involved in disease onset and progression, as well as how it distinguishes between self and foreign cells.

In addition to Yoh and Chanda, authors of the study, Recognition of HIV-1 Capsid Licenses Innate Immune Response to Viral Infection, include Na Rae Ahn and Heather Curry of Scripps Research; Joao I. Mamede of Northwestern University and Rush University Medical Center; Gianguido C. Cianci, Lacy M. Simons, Judd F. Hultquist and Thomas J. Hope of Northwestern University; Derrick Lau, Andrew Tuckwell and Till Bocking of the University ofNew South Wales; Maria T Sanchez-Aparicio and Adolfo Garcia-Sastre of the Icahn School of Medicine at Mount Sinai; Joshua Temple and Yong Xiong of Yale University; Nina V. Fuchs and Renate Konig of Paul-Ehrlich-Institute; Stephanie Gambut of Rush University Medical Center; Laura Riva of Calibr; and Xin Yin of the Harbin Veterinary Research Institute.

Funding was provided by NIAID of the National Institutes of Health, the Gilead Sciences Research Scholars Program in HIV and the German Research Foundation.

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more atwww.scripps.edu.

Recognition of HIV-1 Capsid Licenses Innate Immune Response to Viral Infection

8-Jul-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Immune system uses two-step verification to defend against HIV - EurekAlert

When she was in her 30s, Molly Cassidy was handed a death sentence. Traditional treatments failed to fight the aggressive head and neck cancer that was running rampant through her body. Doctors were out of options, until a clinical trial at the University of Arizona Health Sciences offered a glimmer of hope and, eventually, a second chance at life thanks to immunotherapy.

Immunotherapy is a treatment that uses a person's own immune system to fight cancer, while molecular therapies use drugs and other substances to target specific molecules involved in disease progression. In Cassidys case, she received a personalized cancer vaccine in combination with an immunotherapy drug that helps the immune system fight certain kinds of cancer, and it worked. A year after the UArizona Cancer Center clinical trial ended, there were no traces of cancer left in her body.

Researchers and physician-scientists are increasingly using precision medicine to develop new cell- and gene-based therapeutical options for diseases, building on the idea that the most effective defense against health issues is the bodys natural immune system. At UArizona Health Sciences, the Center for Advanced Molecular and Immunological Therapies, or CAMI, is being developed to advance knowledge of the immunology of cancers, infectious diseases and autoimmune conditions to develop novel strategies for the diagnosis, prevention and treatment of diseases.

Immunotherapy is one of the most promising approaches to cancer treatment, as it has the potential to sidestep the effects of therapies that can compromise patients long-term health and wellness. But cancer isnt the only target researchers, including bioengineer Michael Kuhns, PhD, have in their sights.

Bioengineers solve fundamental problems with technologies that can have many applications, said Dr. Kuhns, associate professor in the UArizona College of Medicine Tucson and member of the BIO5 Institute. If you can make something run more efficiently in certain circumstances for example, make T cells in the immune system more effective at combating a particular disease then the only limit to immunotherapy is your imagination.

Dr. Kuhns research in the Department of Immunobiology focuses on engineering chimeric antigen receptors, or CARs, a relatively new type of gene therapy. He built a biomimetic five-module chimeric antigen receptor, or 5MCAR, to direct killer T cells to target and destroy autoimmune T cells. When tested in a non-obese diabetic mouse model, the 5MCAR T cells recognized and destroyed pathogenic T cells, effectively preventing Type 1 diabetes.

The Center for Advanced Molecular and Immunological Therapies will focus on developing precision therapies that stimulate or suppress the immune system to fight diseases including cancers, infectious diseases and autoimmune conditions.

This technology has clear implications for autoimmune disease, but also for cancer, said Dr. Kuhns, who serves on the 21-member CAMI Advisory Committee. This technology emerged from basic science, is taking hold in the laboratory and is showing promise to go to the clinic. This is a prime example of what we can do.

CAMI will build on UArizona Health Sciences expertise in basic science, translational medicine and investigator-initiated clinical trials to advance immunotherapies research in four areas: cancer, infectious diseases, autoimmune diseases and real-time immune system monitoring.

Other examples of potential research include identifying biomarkers for response to immunotherapy that may help determine the precise drugs to fight specific cancers in individual patients, understanding individual immune responses to autoimmune diseases such as lupus, rheumatoid arthritis or Crohns disease, and creating ways to analyze immune health at the cellular level to identify how individuals might respond to a disease and to predict their health outcomes.

CAMI will serve as the anchor for an innovation district that aims to differentiate Phoenix from other emerging life sciences hubs, establishing the Phoenix Bioscience Core as a center of cell and gene therapy research, startup activity and corporate engagement. Its location is expected to facilitate strong connections with partners such as Arizona State University, Northern Arizona University, the Mayo Clinic and the Translational Genomics Research Institute, among others.

We expect CAMI to be nothing short of a national biomedical research hub, said Michael D. Dake, MD, senior vice president for UArizona Health Sciences. CAMI will be a beacon for people who are involved in this type of research to work, collaborate and engage on the Phoenix Bioscience Core.

The research will take place in connected buildings that are being designed to include laboratories to support translational research, clinical research space and startup incubator space to create a synergistic environment for commercialization opportunities. Student education will be prioritized in learning spaces dedicated to academic programs that will allow CAMI faculty and researchers to mentor and train the next generation of scientists.

There is not a field with more explosive growth than immunotherapy. There is rapid growth in research investment and increased formation of academic and industry partnerships around the world, Dr. Dake said said during a Tomorrow is Here Lecture Series presentation in Phoenix. My hopes are that CAMI is going to provide opportunities to accelerate the development and delivery of revolutionary treatments for the management of cancer, autoimmune and infectious diseases.

We are going to see diversification of drug classes and different types of combination therapies, delivery mechanisms and monitoring, he added. Going forward, I think were going to see a wide array of therapies that are going to be vastly different than any past generations ever had. Suffice it to say, in the future, pills and syringes are going to be obsolete.

Read more:
CAMI Set to Transform Immunotherapy Field Through Research - University of Arizona

* WHO provides technical support to the study on investigating seroprevalence of SARS-CoV-2 and dengue infections in Sri Lankan childrenFri, Jul 8, 2022, 12:23 pm SL Time, ColomboPage News Desk, Sri Lanka.

July 08, Colombo: Sri Lanka too experienced a rapid rise in number of cases and deaths, with the community spread of the Delta variant of the SARS-CoV -2 virus. However, deaths were predominantly seen among adults, with children rarely developing severe disease, as observed in other countries.

Sri Lanka experienced two massive COVID-19 outbreaks due to the Alpha and Delta variants of the SARS-CoV -2 virus, resulting in a large number of individuals being infected in the community. It was estimated that surveillance of SARS-CoV-2 with the Real-time polymerase chain reaction (RT-PCR) testing alone may underestimate the true prevalence of the disease by tenfold. Therefore, conducting a seroprevalence study remained an option for Sri Lanka to determine prevalence of SARS CoV-2 specific antibodies due to infection or vaccines in the country.

Seroprevalence studies help understand the true extent of an outbreak and provide valuable insights in to efforts that help project the trend of future outbreaks, and their transmission dynamics. However, in Sri Lanka, a majority of infections was reported in adults, most of whom experienced more severe and symptomatic infections. On the other hand, true infection rates among children in the country were not clearly known. One of the reasons for this could be limited PCR testing in children, largely because they do not show symptoms following infection with SARS-CoV-2 virus. Also, infection rates could be very different across districts, based on the intensity of transmission reported in different geographical regions.

Considering the above, the Allergy Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura and the Ministry of Health supported by WHO Country Office for Sri Lanka planned a study on seroprevalence of SARS-CoV-2 infections and dengue infections in Sri Lankan children.

In order to submit the study protocol to WHOs Ethical Review Committee, a joint review of study protocols was undertaken by the Unity trial desk of WHO Headquarters, the SEA Regional Office and the WHO country office for Sri Lanka. After revising the study protocol based on WHO recommendations, investigators submitted the finalized protocol to the Regional Review Committee.

The proposed study will help Sri Lanka determine the proportion of children who have been infected with COVID-19 and also with dengue, by studying the presence of antibodies to these viruses in children of different age groups. Additionally, it will determine genetic associations that predispose children to severe disease of dengue. Further, the study will provide information that will help understand how COVID-19 and dengue have spread geographically in the Sri Lankan population.

The seroprevalence in this study will be determined by biological assays, which are both qualitative and quantitative (ELISA, Luminex). The patient data will be collected on clinical features, clinical disease severity and complications.

The findings of this investigation will be used to inform public health response to COVID-19. Specifically, it can provide estimates of otherwise unrecognized SARS-CoV-2 infection in the population, as well as likely susceptibility of the population to further epidemic peaks. The findings may also supplement other supportive evidence used to inform decision-making about vaccine prioritization for target groups, based on demonstrated susceptibility by age groups.

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Sri Lanka : WHO provides technical support to the study on investigating seroprevalence of SARS-CoV-2 and dengue infections in Sri Lankan children -...

Summary: Targeting the GAT3 protein in the thalamus could help block and prevent long-term damage following brain injury.

Source: Gladstone Institute

For days, and even years, after someone suffers a stroke or traumatic brain injury, they have an increased risk of developing epilepsy.

Now, researchers at Gladstone Institutes discovered that star-shaped cells called astrocytes in the thalamus play a key role in making mice with brain injuries susceptible to seizures.

The team also analyzed human post-mortem brain tissue and showed that the same cells identified in mice might be altered in the thalamus of people affected by brain injury and stroke.

The findings,published in the journalScience Translational Medicine,suggest that targeting a protein in these cells could prevent the long-term damage that follows brain injury.

In the aftermath of brain injuries, the thalamus has been relatively understudied compared to other brain regions, saysJeanne Paz, PhD,an associate investigator at Gladstone and senior author of the new study. Im hoping this is just the beginning of many new lines of research about how important this region is in determining how we can help the brain be resilient to consequences of injuries.

A Cascade of Inflammation Deep in the Brain

At the time of a stroke or traumatic brain injury, many cells at the site of the injury die almost immediately. Inflammatory cells and molecules begin to gather, cleaning up the dead cells and molecular debris. In the thalamus, an area deep in the center of the brain that may be far from the site of injury, cells called astrocytes become activated, leading to a cascade of inflammatory changes.

Previous studies from the teamhave shown, in rodent models, that activation of astrocytes in the thalamus is a common consequence of brain injury. However, astrocytes also play key roles that support neurons, including controlling their connections and providing them with nutrients.

In this study, the scientists wanted to determine whether the activation of astrocytes in the thalamus helps the brain recover, leads to additional damage, or has both positive and negative effects.

Astrocytes are so important to the brain that you cant just get rid of them to treat disease, says Frances Cho, a graduate student at Gladstone and UC San Francisco (UCSF), and the first author of the new study. We needed to determine whether we could separate the damaging actions of activated astrocytes from their protective actions.

Focus on the Thalamus

Paz, Cho, and their collaborators hypothesized that activated thalamic astrocytes might play a role in some of the longer-term symptoms of brain injuryincluding an increased risk of seizures and sleep problems. So, rather than study mice with brain injuries, the team initially tested the consequences of activating thalamic astrocytes in otherwise healthy animals.

They found that just activating thalamic astrocytes was enough to cause altered patterns of brain activity similar to those seen after injury, and made the mice susceptible to seizures.

When the researchers then analyzed the molecular properties of the activated astrocytes, in collaboration with the team ofAnna Molofsky, MD, PhD,at UCSF, they discovered that these cells lost a protein called GAT3, which is responsible for regulating the levels of a specific inhibitory neurotransmitter molecule.

As a result, the neighboring neurons were exposed to too much of the neurotransmitter, which resulted in neuronal hyperexcitability and susceptibility to seizures.

We wondered, if the loss of GAT3 in thalamic astrocytes caused neuronal dysfunction, could boosting the level of this protein solve the problem and restore the neurons function? says Paz, who is also an associate professor at UCSF.

To answer this question, the team collaborated withBaljit S. Khakh, PhD,and his group at UCLA who had developed a tool to increase GAT3 specifically in astrocytes. Remarkably, increasing levels of GAT3 specifically in thalamic astrocytes was enough to prevent neuronal hyperexcitability and increased seizure risk caused by activated astrocytes.

The team next tested whether the results held true in mice with brain injuries. Increasing levels of GAT3 in the thalamic astrocytes of these mice also reduced the risk of seizure and the rate of mortality.

These activated astrocytes are quite different in many ways than astrocytes that are not activated, so it was surprising we could pinpoint a single molecular change that we could target to prevent the consequences of brain injury, says Cho.

A Potential Therapeutic

Samples of human thalamus are rarely collected during post-mortem brain biopsies. But, in collaboration withEleonora Aronica, MD, PhD,and her group at the University of Amsterdam, the researchers were able to obtain a small number of post-mortem thalamus samplesthree from individuals with no known brain injuries, three from people who had had a stroke, and four from people with traumatic brain injury.

The post-mortem brains with stroke and traumatic brain injury seemed to have lower levels of GAT3 in their thalamic astrocytes, just as we had seen in the mouse model, says Cho.

We hope that with increased attention to the thalamus, it will become more routine to collect thalamus samples from post-mortem biopsies in the future.

The researchers hope to continue collecting longer-term data on both mice and humans to study the time course of astrocyte activation in the thalamus after brain injury.

Since these changes to the thalamus occur after the initial brain injury, there is a window of time in which clinicians might be able to intervene to stop or reverse themand prevent the increased risk of developing epilepsy, says Paz.

Other authors are Yuliya Voskobiynyk, Allison Morningstar, Bryan Higashikubo, and Agnieszka Ciesielska of Gladstone; Ilia Vainchtein and Francisco Aparicio of UCSF; Diede Broekaart, Jasper Anink, Erwin van Vliet and Eleonora Aronica of University of Amsterdam; and Xinzhu Yu of UCLA.

Funding: The work was supported by funding from the National Institute of Neurological Disorders and Stroke (F31 NS111819, R01 NS096369, R01 R01NS121287, R00 NS078118, R35 NS111583), the National Institute of Mental Health (DP1 MH104069, DP2 MH116507, R01 MH119349), the National Cancer Institute (P30 CA082103), the National Science Foundation (1144247), a UCSF Discovery Fellowship, the Department of Defense (EP150038, EP190020), a Gladstone Institutes Animal Facility grant (RR18928), Pew Charitable Trusts, an EU Seventh Framework Programme EPITARGET grant (602102), an EU Horizon 2020 Research and Innovation Programme Marie Sklodowska-Curie grant (722053), and the Dutch Epilepsy Foundation (project 16-05).

Author: Julie LangelierSource: Gladstone InstitutesContact: Julie Langelier Gladstone Institutes Image: The image is in the public domain

Original Research: Open access.Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents by Jeanne Paz et al. Science Translational Medicine

Abstract

Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury.

Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown.

Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury.

In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury.

Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway.

Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.

Read more from the original source:
Pathway Deep in the Brain Makes It Resilient After Injury - Neuroscience News

We discussed challenges to initiate and maintain researcheradvocate relationships, and proposed short- and long-term solutions (Table 1):

The first challenge is that it is not clear why patient advocates should be included in research. Sometimes researchers feel that their work is too far removed from the patient or that the patient advocate may not be able to provide anything valuable to the research. There are plenty of resources that describe the value of these relationships, but more can be done to ensure the value is demonstrated8,12,13.

In the short-term, anecdotal stories can support researchers realization of the value of working with patient advocates. Groups that require patient advocate involvement for funding, such as the Department of Defense Breast Cancer Research Program, should supply clear, public statements describing the benefit of including patient advocates in the research process. All disease-related research funding groups should encourage or require patient advocate input and involvement in grant projects, both to support writing the project plan and as part of developing the hypothesis, designing the project, and supporting dissemination of the findings. Researchers should ensure that they avoid engaging in performative advocacy (having a token advocate) through clear and frequent communication with the patient advocate. Performative advocacy is when patient advocates are included in research discussions to fulfill a requirement by simply saying a patient advocate was present, rather than listening to the patient advocates suggestions and incorporating their feedback into the study.

In the long-term, it would help to initiate a research project whose goal is to evaluate the added benefit of researchers working with patient advocates. This type of work should consider endpoints such as funding, publications, and overall satisfaction with work. Additionally, clinical endpoints may also improve and thus should be measured including translation to the clinic and engagement of diverse populations in related trials.

The second challenge is that researchers are worried about saying the wrong thing. During the panel discussions, one researcher said, its intimidating. I dont want to fail the patients. I want what Im doing to be meaningful. Some researchers fear working with a patient advocate in case they want a cure or have unrealistic expectations of how quickly (or how slowly) the research is going to move, which may feed into the researchers concern of failure. Metastatic disease is currently not curable, and many (but not all) patients will have limited time to live, and thus many researchers fear that they will say something that is insensitive given this challenging situation.

Open lines of communication are extremely important as they establish expectations from the start that everyone is learning from each other and ensure the environment is a safe space. Both groups should feel that they can ask questions they may feel like others know the answer to. They should also feel comfortable respectfully correcting others within their own areas of expertise. Our discussions noted that scientists have not historically been trained to communicate with nonscientists, but there is increasing recognition of this shortcoming, and current trainees will hopefully reap the benefits of increased attention to this matter13,14.

There is a need for training programs in which researchers learn how to work with patient advocates. This could be a workshop at a conference or annual retreat, or part of a class about communication. Conferences like the American Association for Cancer Research (AACR) Annual Meeting, the American Society for Clinical Oncology (ASCO) Annual Meeting, the San Antonio Breast Cancer Symposium (SABCS), and the Metastasis Research Society (MRS) Biennial Congress should consider including training sessions on best practices for working with patient advocates at their events.

The third challenge is that researchers do not know where to meet patient advocates. Initially, connecting with patient advocates can be challenging for researchers. It can happen through a variety of venues, though, through formal programs like those at Georgetown University8 and Huntsman Cancer Institute or informally through forums like Twitter by following #BCSM and other cancer-specific social media tags.

In the short-term, researchers should review established advocate programs to determine if they would benefit from initiating similar programs at their institutions. Georgetown University and Huntsman programs are examples where patient advocates meet regularly to support research at their respective cancer centers by providing a forum for researchers to explain their work and meet new patient advocates. Patient advocates could be invited to annual retreats to give those who do not normally work with advocates a chance to establish collaborations. Kansas University developed a researcher/patient advocate toolkit called PIVOT (Patient and Investigator Voices Organizing Together) AdvocateResearcher Working Together Toolkit15, which provides additional best practices for establishing relationships. The National Cancer Institute Specialized Program of Research Excellence (SPORE) grants are structured to bring basic research to a Phase I Trial and SPORE applications are required to include advocates.

There are scientific conferences that support patient advocate participation and interaction with researchers such as the Metastatic Breast Cancer Research Conference and AACRs ScientistSurvivor Program. Additionally, an organization run by patient advocates called Guiding Researchers and Advocates to Scientific Partnerships (GRASP) fosters patient advocate and researcher interactions through poster discussions at conferences. Conferences also benefit from facilitating opportunities for patient advocates and research scientists to have formal interactions through panel discussions and informal interactions like coffee chats or happy hours.

In the long-term, it would be beneficial to develop a national database for researchers and patient advocates to connect that includes the persons interests, location, and time commitment. Groups like GRASP have already started this type of database that includes hundreds of patient advocates and researchers. It would be helpful if this database were turned into a tool or phone app that connects researchers and patient advocates through a series of questions similar to something like match.com. Developers should work towards being inclusive of research on multiple cancer types and consider piloting the tool or app in a specific region to optimize it before opening it up nationwide.

The final challenge is that researchers do not know how to include patient advocates in research. Once a researcher has met a patient advocate, they may not know how to continue to include the patient voice in their work. It is extremely important to establish open lines of communication as groundwork for collaboration, and ensure patient advocates are appropriately compensated. Both researchers and patient advocates should establish their expectations when starting to work together. It is important to understand whether the collaboration will be a short- or long-term engagement and both parties should consider time commitments with regard to frequency of meetings as well as the length of meetings.

Ideally, researchers should begin working with patient advocates early in their career16. To support these relationships, institutions should build programs to support that connection. A few examples of success include:

Cornell Community Cancer Partnership: Cornell has developed a program that brings community members affected by, or interested in, cancer together with basic research Ph.D. students16. They have monthly seminars where graduate students give presentations in common language or community members describe their experiences living with cancer17. The program focuses on science communication and exposing trainees to the human side of cancer.

Cancer Trainee Advocate Program (CTAP): This program is a resource for how to get trainee programs started at institutions and provides a few examples. The goal is to bring patient advocates from the community together with trainees to have initial discussions about experiences with cancer and their research, respectively.

Cellular and Molecular Basis of Disease Course in the Cellular and Molecular Medicine Ph.D. Program at Johns Hopkins University: During the first year of graduate study, M.D. or Ph.D. faculty members present lectures on human diseases and often bring in a patient to share their perspective. These studentpatient interactions are described by students as a highlight of their educational experience.

There are many other examples, both at the national and local level9. Once relationships are established, researchers should create a process for maintaining collaboration. Patient advocates enjoy being involved with every step of the research process and including advocates throughout the grant writing process avoids performative advocacy. Researchers should consider patient advocates involvement in grants early in the process, not only to support the merit of the grant in the review process, but as a true partner as the grant progresses. This likely involves including them in the budget and/or as a co-author on publications, as appropriate. Having a long-term relationship supports the organic process of patient advocate involvement, which allows time for advocates to become partners in research as the project progresses. A few suggestions for long-standing collaboration are included in Table 2.

It is important for researchers to consider ways to compensate patient advocates for their time, which may include paying for service, covering travel, or inclusion in a manuscript. Researchers should discuss compensation with patient advocates but understand that there are complexities such as the impacts of receiving disability benefits. The field would benefit from more comprehensive discussions and guidance regarding compensation for patient advocates, including intricacies, appropriate amounts, where funding for advocates comes from.

In the long-term, it would help to have clearer definitions of roles for patient advocates receiving compensation or providing effort in grant applications and research projects. The National Cancer Institute (NCI) should consider explaining how advocacy fits into their NCI Comprehensive Cancer Center designation rubric to more clearly demonstrate the value these relationships bring to cancer centers. There is a potential opportunity to include patient advocates in the context of community outreach and engagement (COE). Laying out expectations of researchers working with patient advocates, as well as the purpose for the interactions, would be a great benefit to the community and improve cancer research overall.

In conclusion, our analysis identified two major barriers to research scientist working with patient advocates. The first is that research scientists do not know how to initiate the relationship and the second is that they are unsure of what the relationship should look like. For cancer researchers, we have highlighted ways to collaborate with patient advocates and outlined examples of established best practices from multiple institutions, a resource that has not been comprehensively outlined before. We hope this document will inspire new relationships and programs as we move towards ensuring the patient voice is considered along the continuum of research. While focused, our discussions were not quantitative in nature. To support implementation of programs, academic centers would likely benefit from a more quantitative description of the approach and outcomes. Future studies should collect detailed demographics and expand the group to diverse demographic groups, especially with respect to gender, age, income, and race. Ultimately, these relationships will improve cancer research and more quickly accomplish our collective goal of improving lives of those who have been diagnosed with cancer. We recommend this relationship would be incorporated as part of the infrastructure of the basic research in cancers.

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Improving the odds together: a framework for breast cancer research scientists to include patient advocates in their research | npj Breast Cancer -...

More than 426,000 people have signed a petition against the end of free testing kits, which has now been delivered to Downing Street

Covid rates in the UK have surged recently - due to the BA.4 and BA.5 variants - leading to campaigners calling for free tests to return.

Dr John Puntis, co-chair of Keep Our NHS Public and lead of the petition, said the recent rise of Covid cases made the petition to bring back free lateral flow tests even more relevant.

He said that although there are fewer cases of serious illness and death from Covid, there are still 3.7 million people in England classed as clinically extremely vulnerable from Covid.

He added that more than two million people in England who have had long Covid often live with the devastating effects on their quality of life and ability to work.

Dr Puntis said the petition sends a strong message to Prime Minister Boris Johnson that there is much more to be done and that living with Covid has to be a lot more than just vaccination.

It must include widespread testing, free lateral flow tests, sick pay and support for self-isolation, mask wearing in crowded indoors, flexible working, and clean air through improved ventilation systems. It is time to put public health at the heart of our response to Covid, Dr Puntis added.

Martin Michaelis, professor of molecular medicine at the University of Kent, also agreed that free testing for Covid needs to be made publicly available on a widespread basis again.

He said if the spread of Covid is to be reduced then people need to know whether they are infected and may infect others.

Without tests, nobody can know whether they carry the virus or not, he added.

Prof Michaelis said that due to the high level of pre-existing immunity - which is down to vaccinations and previous infections - many people do not experience symptoms when they are infected with Covid.

He added that even those who do have symptoms cannot know with certainty whether they have Covid or another respiratory infection.

Many people will therefore unknowingly spread Covid if they do not have an easy opportunity to test themselves, he added.

He also said that although many people have a high level of immune protection from Covid, there is a significant proportion of the population whose immune system is not working properly and who cannot protect themselves by vaccination.

These people are put at a much higher risk when the Covid levels are high in the population, said Prof Michaelis.

Since people can only avoid spreading the virus when they know that they have it, free testing is an important measure that reduces Covid spread and, in turn, the risk of future devastating Covid waves, he added.

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Should Covid tests be free again? Thousands sign petition as cases surge in UK - NationalWorld

The recent experience of the COVID-19 pandemic and the ensuing vaccine development have drawn our attention to the system that keeps us alive: immunity. However, our immune system does more than fight against microbes. The new textbook Molecular Immunology: How Science Works by Professor Carsten Carlberg and Dr Eunike Velleuer provides an essential background in molecular immunology. This includes the basic principles and underlying processes of immunity against bacteria and viruses, immune responses to cell and organ transplants, the overboarding immune activation in allergies and autoimmune reactions, as well as the way how a properly functioning immune system protects us against cancer.

Understanding these mechanisms will highlight that a fight against viruses uses the same mechanisms as the battle against thousands of transformed cancer cells arising every day in each of us, the authors remark.

Our immune system is composed of biological structures like the lymphatic system and bone marrow, as well as cellular immunity mediated by cell types such as leukocytes and humoral immunity mediated by proteins such as antibodies and complement proteins. The perfect balance of these components protects us against infectious diseases and cancer. Molecular immunology aims to understand the collective and coordinated response of these cells and proteins to substances that are foreign to our body. The main purpose of this immune response is the fight against microbes, such as viruses, bacteria, fungi and parasites. However, the example of allergic reactions, which nowadays are getting continuously more common, demonstrates that also non-microbial molecules can induce a strong reaction of our immune system. Moreover, incorrect reactions of the immune system can lead to autoimmune diseases, such as type I diabetes and multiple sclerosis. Immune responses can cause tissue injuries that are more harmful than the effects of pathogenic microbes. These collateral damages may be even fatal, such as in the case of bacterial sepsis or strong responses to SARS-CoV-2 infections.

The different chapters of the book explain the cellular basis of immunology, the key molecules mediating the effector functions of B and T cells, and how molecular immunology is associated with infections caused by bacteria and viruses, organ transplantation, allergy and autoimmunity as well as different types of cancers.

We hope that readers will enjoy this rather visual book and get as enthusiastic as the authors about life and its protection reflected in the fine-tuned molecular immunology.

Molecular Immunology: How Science Works is the fifth textbook in the series How Science Works co-authored by Professor Carlberg. The earlier books in the undergraduate book series are Cancer Biology: How Science Works, Mechanisms of Gene Regulation: How Science Works, Human Epigenetics: How Science Works and Nutrigenomics: How Science Works. They are linked to the lecture courses in Molecular Immunology, Molecular Medicine and Genetics, Cancer Biology and Nutrigenomics given by Professor Carlberg at the University of Eastern Finland in Kuopio. The book series now covers each lecture course.

Carsten Carlberg graduated in 1989 with a PhD in biochemistry at the Free University Berlin. After positions as postdoc at Roche in Basel, group leader at the University of Geneva and docent at the University of Dsseldorf, he is since 2000 full professor of biochemistry at the University of Eastern Finland in Kuopio. His work focuses on the mechanisms of gene regulation by nuclear hormones, in particular on vitamin D. At present, Professor Carlbergs projects focus on the epigenome-wide effects of vitamin D on the human immune system in the context of cancer.

Eunike Velleuer graduated in 2006 as MD at the University of Dsseldorf and specialized in 2016 in pediatric hemato-oncology. At present, she serves as senior physician at the Helios Childrens Clinic Krefeld as well as a research associate at the University of Dsseldorf. Her special clinical focus is the cancer predisposition syndrome Fanconi anemia. Herein, her research interest is early detection and prevention of oral squamous cell carcinoma and identifying patients with Fanconi anemia at risk. Furthermore, Dr. Velleuer is interested in increasing patients resilience and finding alternative ways for long-lasting empowerment.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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New textbook addresses the timely topic of molecular immunology - EurekAlert

People are exposed to low-dose radiation in many ways: having a CT scan, working as a medical technician or in a nuclear power plant, or living in an area contaminated by radiation. The health effects of these low-dose exposures are not well understood but a revitalized research program could change that.

Decades of research have revealed a number of adverse health effects that have occurred in individuals exposed to high doses of radiation, with most of this work focused on cancer. Much less is understood about the effects of low doses experienced by millions of Americans, although there is increasing evidence of its links to cardiovascular disease, neurological disorders, immune dysfunction, and cataracts, as well as cancer. These possible connections raise questions as to whether the public and workers are adequately protected by current radiation standards and regulations.

We and a group of colleagues working in radiation biology, dosimetry, epidemiology, biotechnology, economics, biostatistics, environmental health, and other disciplines released a report in early June detailing the limitations in whats known about the health effects of exposure to low-dose radiation. This group, assembled by the National Academies of Science, Engineering, and Medicine at the request of Congress, presented a plan to revitalize low-dose radiation research in the U.S., which has stalled in recent years, including how this research could be coordinated, its essential elements, and high-priority areas needed to fill in some of the knowledge gaps.

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The first step we recommend is to ensure adequate funding for this important work. The $5 million appropriated for the U.S. Department of Energys (DOE) low-dose radiation program in 2021 and 2022 is not sufficient even to get a research program off the ground, let alone fund the research itself. But with adequate funding, we estimate the DOE could implement a revitalized, strategic research program within just two years.

Significant investments over a sustained period spanning more than a decade will be required, with an estimated cost of about $100 million a year for the next 15 years. This funding would help establish a structure for research, fund competitive proposals in epidemiological and biological research, support engagement with affected communities, and train and retain a new generation of radiation scientists across a range of disciplines.

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One critical finding of the report is that a revitalized low-dose research program would be able to leverage recent development in other fields, such as increased understanding of the cellular and molecular processes that enable development of human adverse health effects; new epidemiological methods and databases; and powerful new biological, measurement, and computational tools that previous researchers did not have at their disposal.

Epidemiological research can take advantage of increasingly accessible electronic databases and information on disease presence and severity from the internet of medical things, as well as more precise molecular classification of human diseases, and improved estimates of radiation doses, among other advances. These approaches could also aid in identifying factors such as inherited genetic variants or lifestyles that can modify the risks of low-dose radiation exposure.

Biological research can exploit new abilities to manipulate cells, tissues, and animals to understand how biological responses change with the level of exposure; to directly measure cellular and molecular changes resulting from exposure to low dose radiation; and to establish causal links to radiation exposure. The use of advanced measurement tools could help reveal the mechanisms that control biological responses to low-dose radiation.

Join Mohana Ravindranath, STAT's health tech correspondent, on June 29 at 1:00 p.m. ET to examine how technologies like telemedicine and big data may help doctors reach patients who currently dont get high-quality care.

We believe this research requires a long-term federal commitment, because the effects of low-dose radiation may take years or decades to manifest themselves. It will also take time to build and sustain a community of radiation effects experts who will be available to assist in the management and mitigation of the health effects of radiation exposures.

To be successful, any federal office leading the program will need to be dedicated to scientific independence, transparency, and stakeholder participation. This is especially important as science seeks to provide answers to concerned individuals and to communities that have been involuntarily exposed to radiation: indigenous communities, veterans exposed to radiation during military operations, nuclear workers, and others affected by the legacy of U.S. nuclear weapons testing and production. These communities had a strong voice in our report, and we learned how essential trust and meaningful involvement in research is to them.

Our committee also acknowledged concerns from communities affected by low-dose radiation regarding the Department of Energys leadership of low-dose radiation research, such as its conflicts of interest due to its work with the nuclear weapons program and promoting nuclear energy. While our committee was specifically asked to develop a research program led by DOE, our report notes that both it and the National Institutes of Health (NIH) have historically supported radiation research. While the DOEs Office of Science has de-prioritized this research in recent years, the NIHs health research capabilities are well established, and the NIH is widely trusted by the scientific community and has no perceived conflicts of interest regarding radiation research from the public.

Our report is clear: If a revitalized low-dose research program moves forward under DOE leadership, its performance should be independently evaluated. If the agencys management of the program falls short, other agencies, including the NIH, should be considered to lead the program instead.

An opportunity exists to greatly expand the understanding of how low-dose radiation exposure affects health. A federally-coordinated program will provide valuable information, and reveal whether current regulations and protections are adequate to keep Americans safe from the effects of low-dose radiation. Now is the time to revitalize this research.

Joe Gray is a professor emeritus at the Oregon Health and Science University and University of California, San Francisco, and chair of the National Academies of Sciences, Engineering, and Medicines Committee on Developing a Long-Term Strategy for the Low-Dose Radiation Research in the United States. Lindsay Morton is a senior investigator and deputy chief of the Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and a member of the committee. Gayle Woloschak is a professor of radiation oncology at Northwestern University in Chicago, adjunct professor of religion and science at Lutheran School of Theology Chicago and at Pittsburgh Theological Seminary, and a member of the committee.

Link:
The U.S. needs to revitalize research on the health effects of low-dose radiation - STAT

First published in the June 16 print issue of the Outlook Valley Sun.

Every day for work, Dr. Matthew Lew returns to where it all began.His office, the rare private family practice, is based on the campus of Adventist Health Glendale, where he and his siblings were all born. That practice, Lew Medical, was founded by his father, Dr. Edmund Lew, with whom Matthew Lew has partnered to lead and eventually take over the business.By his own admission, father did not influence son, at least not deliberately, in picking family medicine as a specialty. However, its clear that the La Caada Flintridge men were cut from the same cloth.It seems like an overused term, treating the whole person, but in fact, my orientation to dealing with a problem really kind of takes into account all of the different issues that people would have, how they relate to it psychologically, all the different systems as they relate to one another, Edmund Lew said in an interview this week. It just seemed to make sense to me that if I was going to be a healer of some sort that I would have to take into account how the body works together but separately in its own system. Treating the whole person seemed to be the best way to help people and resolve their issues.

Plus, he added, I like everything, so it was difficult to actually choose a specialty.Similarly, Matthew Lew found value in seeking a broad, holistic treatment of people. As an undergraduate student at Brigham Young University, he took two years off to embark on a proselyting mission in Guatemala for the Church of Jesus Christ of Latter-day Saints. Matthew Lew said based on his enjoyment of helping others find spiritual awakenings, he felt he would equally relish healing of the body as well.Family medicine it was, then.I love talking to people. I love meeting new people, and its a great way to just meet a whole different bunch of people, Matthew Lew explained. My patients have great and very interesting backgrounds, which is really cool, and I just love interacting with them. In medical school, I kind of liked everything except for delivering babies, he admitted so family medicine is one way to do everything. It was nice not to be restricted, like if I was in a specialty.Matthew Lew, a graduate of La Caada High School, ultimately earned his bachelors degree in molecular biology from BYU and then earned his medical degree from American University in the Caribbean. He was chief resident of the family medicine program while completing his residency at Eisenhower Health in Rancho Mirage.Edmund Lew, who was raised in Silver Lake, graduated from Loyola High School and later earned his bachelors degree in psychology from the University of San Francisco. He then earned his medical degree from Chicago Medical School and did his three-year residency at then-Glendale Adventist Medical Center during which his son was born at the hospital.After he finished medical school, Matthew Lew joined his father at Lew Medical in August 2019.I feel like everyones always asking me, like, How is working with dad? trying to get some inside scoop or good stories, he said. We get along really well. We see each other on the weekends, with our families. Its kind of a boring relationship a good relationship.His father chimed in, with a light chuckle: We dont close the doors, put on the gloves and duke it out.The Lews are both determined to keep alive their unique practice, which in spite of being located at the Adventist Health campus remains independent of the hospital and, to hear them say it, is among the few such private family practices around anymore.Either theyre being bought out by big groups or by hospitals, so its a very different dynamic, Matthew Lew explained. I feel like its rural medicine in the suburbs, because we kind of do everything. We see our patients in the hospital. We see them in the office. We see them in skilled nursing facilities, assisted living, et cetera.We make house calls as well, Edmund Lew added. Most people think, who makes house calls anymore?

Back to Matthew Lew: Its a dying practice, that old school medicine.There just is much to be gained with treating patients where they are and where theyre at, with whatever condition they have, Edmund Lew elaborated. Were going to continue that concept because it really is the best for the patient. That approach allows us to keep patients out of emergency rooms and out of hospitals. Theyre able to contact us at home early on so we can prevent them from having complications of whatever condition they have.Matthew Lew, now married and himself a father of three, still lives in LCF, his youngest now at La Caada Elementary School. They live five minutes from his parents Five minutes including strapping them in the car, Edmund Lew quipped and its an arrangement all are pleased with. Their proximity and work arrangement allowed Edmund Lew to take a recent two-week trip to Africa, and he plans on returning the favor when Matthew Lew and his family vacation in Hawaii soon.Its funny. You grow up in an area and you always want to get out and go somewhere else, right? Well, you go somewhere else, and you look back and start getting in the next phase of your life, like Hey, I want to raise a family, wheres a good place to raise a family? Matthew Lew recalled. A lot of people reminisce about their hometown and thats what I did. I always had a plan of coming back and working here anyway, so it kind of worked out.Edmund Lew, only 68 and not retiring anytime soon, said he is nonetheless preparing his son to fully inherit the practice. He said he is influenced by his own father, who owned a dry cleaner and employed 30, when it comes to running the business and managing his employees like an extension of his own family.Still, Matthew Lew may have to wait a while.With Gods help and with treating myself well working out five days a week, trying to eat well, keeping myself in decent shape I dont know anything else that I would do in retirement that would be as rewarding as what Im doing now, Edmund Lew said. Gardening, I can only do for a little while. Traveling, you can only do for a little while.Soon, their family medicine practice will add even greater emphasis on family. Matthews younger brother is currently studying to be a registered nurse and will embark on family nurse practitioner school this fall.When hes done there, he has a job waiting for him.

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It's All in the Family for Father-Son Doctors Outlook Valley Sun - outlookvalleysun.outlooknewspapers.com