Broadly inhibitory antibodies to severe malaria virulence proteins.

Malaria pathology is driven by the accumulation of Plasmodium falciparum-infected erythrocytes in microvessels. This process is mediated by the polymorphic erythrocyte membrane protein 1 (PfEMP1) adhesion proteins of the parasite. A subset of PfEMP1 variants that bind to human endothelial protein C receptor (EPCR) through their CIDRα1 domains is responsible for severe malaria pathogenesis.

The bio-artificial pancreas to treat type 1 diabetes: Perspectives from healthcare professionals in the Netherlands.

Aims: Healthcare professionals are relevant stakeholders because of their gatekeeper role in the clinic. This study aims to explore their perspectives on the potential future clinical implementation of the bio-artificial pancreas (BAP) for people with type 1 diabetes, and suitable target groups.

Methods: Semi-structured interviews were conducted with 17 healthcare professionals, including endocrinologists, nurses, and pancreas transplant surgeons.

Differences in phenotype between long-lived memory B cells against Plasmodium falciparum merozoite antigens and variant surface antigens.

Plasmodium falciparum infections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in ten Ugandan adults before and after local reduction of P.

Clinical Translation and Implementation of a Bioartificial Pancreas Therapy: A Qualitative Study Exploring the Perspectives of People With Type 1 Diabetes.

Background: The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients' expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation.

Research Design And Methods: Semistructured interviews were conducted with 24 participants diagnosed with T1D.

Should Patients Be Allowed to Pay Out of Pocket? The Ethical Dilemma of Access to Expensive Anti-cancer Treatments in Universal Healthcare Systems: A Dutch Case Study.

With the increasing prices of newly approved anti-cancer treatments contributing to rising healthcare costs, healthcare systems are facing complex economic and ethical dilemmas. Especially in countries with universal access and mandatory health insurance, including many European countries, the organizing of funding or reimbursement of expensive new treatments can be challenging. When expensive anti-cancer treatments are deemed safe and effective, but are not (yet) reimbursed, ethical dilemmas arise.

Whole genome sequencing as a ticket to cancer treatment in the Netherlands: Are inequalities in access to molecular diagnostics unfair?

Whole genome sequencing (WGS) of a tumour may sometimes reveal additional potential targets for medical treatment. Practice variation in the use of WGS is therefore a source of unequal access to targeted therapies and, as a consequence, of disparities in health outcomes. Moreover, this may even be more significant if patients seek access to WGS by paying a relatively limited amount of money out of pocket, and sometimes effectively buy themselves a ticket to (very) expensive publicly funded treatments.

Differences in phenotype between long-lived memory B cells against merozoite antigens and variant surface antigens.

infections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in Ugandan adults before and after local reduction of transmission.

Beyond severity: utility as a criterion for setting the scope of RGCS.

Reproductive genetic carrier screening (RGCS) allows prospective parents to identify and act upon their chances of having a child with a genetic condition. In deciding which genetic conditions to include in RGCS, severity is often used as a criterion. However, the concept is inherently complex, subjective and multidimensional, and determinations of severity will remain intractably contested.

Public Opinions on Removing Disincentives and Introducing Incentives for Organ Donation: Proposing a European Research Agenda.

The shortage of organs for transplantations is increasing in Europe as well as globally. Many initiatives to the organ shortage, such as opt-out systems for deceased donation and expanding living donation, have been insufficient to meet the rising demand for organs. In recurrent discussions on how to reduce organ shortage, financial incentives and removal of disincentives, have been proposed to stimulate living organ donation and increase the pool of available donor organs.

Ready for polygenic risk scores? An analysis of regulation of preimplantation genetic testing in European countries.

Study Question: Would the different regulatory approaches for preimplantation genetic testing (PGT) in Europe permit the implementation of preimplantation genetic testing using polygenic risk scores (PGT-P)?

Summary Answer: While the regulatory approaches for PGT differ between countries, the space provided for potential implementation of PGT-P seems limited in all three regulatory models.

What Is Known Already: PGT is a reproductive genetic technology that allows the testing for hereditary genetic disorders and chromosome abnormalities in embryos before implantation. Throughout its history, PGT has largely been regarded as an ethically sensitive technology.

'Empathy counterbalancing' to mitigate the 'identified victim effect'? Ethical reflections on cognitive debiasing strategies to increase support for healthcare priority setting.

Priority setting is inevitable to control expenditure on expensive medicines, but citizen support is often hampered by the workings of the 'identified victim effect', that is, the greater willingness to spend resources helping identified victims than helping statistical victims. In this paper we explore a possible cognitive debiasing strategy that is being employed in discussions on healthcare priority setting, which we call 'empathy counterbalancing' (EC). EC is the strategy of directing attention to, and eliciting empathy for, those who might be harmed as a result of one-sided empathy for the very ill who needs expensive treatment.

MALARIA-WHY DO MOSTLY CHILDREN GET SICK?

Did you know that micro-organisms can live in blood? parasites can infect red blood cells and cause a serious disease called malaria. This disease is mostly seen in young children living in Africa. Sick children have a fever, aches, can feel very tired, and in bad cases, they can even die from malaria.

Ethics of access to newly approved expensive medical treatments: multi-stakeholder dialogues in a publicly funded healthcare system.

Due to rising healthcare expenditures, countries with publicly funded healthcare systems face challenges when providing newly approved expensive anti-cancer treatments to all eligible patients. In the Netherlands in 2015, the so-called Coverage Lock (CL), was introduced to help safeguard the sustainability of the healthcare system. Since then, newly approved treatments are no longer automatically reimbursed.

Broadly inhibitory antibodies against severe malaria virulence proteins.

pathology is driven by the accumulation of parasite-infected erythrocytes in microvessels. This process is mediated by the parasite's polymorphic erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. A subset of PfEMP1 variants that bind human endothelial protein C receptor (EPCR) through their CIDRα1 domains is responsible for severe malaria pathogenesis.

Defusing the legal and ethical minefield of epigenetic applications in the military, defense, and security context.

Epigenetic research has brought several important technological achievements, including identifying epigenetic clocks and signatures, and developing epigenetic editing. The potential military applications of such technologies we discuss are stratifying soldiers' health, exposure to trauma using epigenetic testing, information about biological clocks, confirming child soldiers' minor status using epigenetic clocks, and inducing epigenetic modifications in soldiers. These uses could become a reality.

Atypical B cells consist of subsets with distinct functional profiles.

Atypical B cells are a population of activated B cells that are commonly enriched in individuals with chronic immune activation but are also part of a normal immune response to infection or vaccination. To better define the role of atypical B cells in the human adaptive immune response, we performed single-cell sequencing of transcriptomes, cell surface markers, and B cell receptors in individuals with chronic exposure to the malaria parasite , a condition known to lead to accumulation of circulating atypical B cells. We identified three previously uncharacterized populations of atypical B cells with distinct transcriptional and functional profiles and observed marked differences among these three subsets in their ability to produce immunoglobulin G upon T-cell-dependent activation.

Single-cell quantitative bioimaging of liver stage translation.

parasites cause malaria in humans. New multistage active antimalarial drugs are needed, and a promising class of drugs targets the core cellular process of translation, which has many potential molecular targets. During the obligate liver stage, parasites grow in metabolically active hepatocytes, making it challenging to study core cellular processes common to both host cells and parasites, as the signal from the host typically overwhelms that of the parasite.

Expanded access to investigational drugs in psychiatry: A systematic review.

Some psychiatric patients have exhausted all approved treatment options. Numerous investigational drugs are currently being developed and tested in clinical trials. However, not all patients can participate in clinical trials.

[Prioritisation in health care: An ethical perspective].

Scarcity is an increasingly pressing problem currently in health care. To help address growing waiting lists, some hospitals in the Netherlands have begun applying triage of referrals for specialist care by primary care physicians: Which patients must be seen in the hospital, and which patients may just as well be treated in primary care settings? Does this new practice of more stringent triage fall within the scope of normal good care provision, or is something else - such as implicit rationing - at play? This paper analyses decision-making about care from an ethical perspective, using various justice theories, including utilitarianism, egalitarianism, sufficientarianism, and prioritarianism.

The Relevance of Advanced Therapy Medicinal Products in the Field of Transplantation and the Need for Academic Research Access: Overcoming Bottlenecks and Claiming a New Time.

The field of transplantation has witnessed the emergence of Advanced Therapy Medicinal Products (ATMPs) as highly promising solutions to address the challenges associated with organ and tissue transplantation. ATMPs encompass gene therapy, cell therapy, and tissue-engineered products, hold immense potential for breakthroughs in overcoming the obstacles of rejection and the limited availability of donor organs. However, the development and academic research access to ATMPs face significant bottlenecks that hinder progress.

Clinical Translation of Bio-Artificial Pancreas Therapies: Ethical, Legal and Psychosocial Interdisciplinary Considerations and Key Recommendations.

The field of regenerative medicine offers potential therapies for Type 1 Diabetes, whereby metabolically active cellular components are combined with synthetic medical devices. These therapies are sometimes referred to as "bioartificial pancreases." For these emerging and rapidly developing therapies to be clinically translated to patients, researchers must overcome not just scientific hurdles, but also navigate complex legal, ethical and psychosocial issues.

Awe and anxiety for cancer cells: connecting scientists and patients in a holistic approach of metastasis research.

Background: Metastatic cancer is often experienced by patients as a death sentence. At the same time, translational scientists approach metastasis also as an interesting phenomenon that they try to understand and prevent. These two sides of the same coin do not mask the considerable gap that exists between the laboratory world of scientists and the life world of patients.

Can Voluntary Health Insurance for Non-reimbursed Expensive New Treatments Be Just?

Public healthcare systems are increasingly refusing (temporarily) to reimburse newly approved medical treatments of insufficient or uncertain cost-effectiveness. As both patient demand for these treatments and their list prices increase, a market might arise for voluntary additional health insurance (VHI) that covers effective but (very) expensive medical treatments. In this paper, we evaluate such potential future practices of VHI in public healthcare systems from a justice perspective.