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"Becker, L."
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Availability of oral antivirals against SARS-CoV-2 infection and the requirement for an ethical prescribing approach
The first two oral antivirals, molnupiravir and nirmatrelvir–ritonavir, are now becoming available in many countries. These medicines will be indicated to treat mild-to-moderate COVID-19 in non-hospitalised patients who are at high risk of progressing to severe COVID-19. These antivirals should be prescribed within 5 days of symptom onset, and after SARS-CoV-2 infection has been confirmed. However, the availability of these antivirals will be scarce for some time due to manufacturing constraints. Each country should establish a policy on the conditions under which these antivirals can be prescribed. Such a policy should be based on the fulfilment of five ethical elements: transparency, relevance, appeals, enforcement, and fairness. Following the principles of distributive justice, molnupiravir and nirmatrelvir–ritonavir should be prescribed according to a hierarchy of predicted efficacy, ideally on the basis of an evidence-based scoring system. The placebo-controlled randomised trials that supported the temporary authorisation of these two antivirals were conducted in unvaccinated patients with COVID-19, so an evidence-based prescription practice would only use these drugs for unvaccinated patients until further data become available. However, in the countries that authorised these antivirals in 2021 (the UK and the USA), both vaccinated and unvaccinated patients meeting particular requirements have access to these antivirals. Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible and these policies should be regularly updated. The effectiveness of these antivirals against the omicron variant of SARS-CoV-2 must be urgently assessed. Once implemented, molnupiravir and nirmatrelvir–ritonavir must show their effectiveness and safety in the real world, and health systems must be adequately adapted for the correct use of these antivirals.
Journal Article
Pooling of samples for testing for SARS-CoV-2 in asymptomatic people
Sufficient molecular diagnostic capacity is important for public health interventions such as case detection and isolation, including for health-care professionals.1 Protocols for RNA RT-PCR testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became available early in the pandemic, yet the infrastructure of testing laboratories is stretched and in some areas it is overwhelmed.2 We propose a testing strategy that is easy to implement and can expand the capacity of the available laboratory infrastructure and test kits when large numbers of asymptomatic people need to be screened. Viral load during symptomatic infection with SARS-CoV-2 was investigated by Zou and colleagues.3 To analyse the effect of pooling samples on the sensitivity of RT-PCR, we compared cycle threshold (Ct) values of pools that tested positive with Ct values of individual samples that tested positive. The Ct values for both E-gene and S-gene assays in pools and individual positive samples were below 30 and easily categorised as positive.
Journal Article
المدينة الفاضلة عند فلاسفة القرن الثامن عشر
يستعرض كارل بيكر في هذا الكتاب تصورات الفلاسفة حول المدينة الفاضلة خلال القرن الثامن عشر، وهو عصر يتسم بالتحولات الفكرية الكبرى. يتناول الكتاب أفكار عدد من المفكرين الذين ساهموا في تطوير رؤية المدينة المثالية وكيفية تحقيقها، بناء على مبادئ فلسفية واجتماعية، يبدأ الكتاب بمراجعة مفهوم المدينة الفاضلة في الفلسفة، مقدما خلفية تاريخية حول تطور هذا المفهوم منذ العصور القديمة إلى القرن الثامن عشر. يوضح كيف أن مفهوم المدينة الفاضلة كان يعكس الطموحات والأيديولوجيات السياسية والفلسفية في تلك الفترة، يناقش الكتاب أفكار مجموعة من الفلاسفة البارزين في القرن الثامن عشر، مثل فولتير، روسو، وكوندورسيه، حول مفهوم المدينة الفاضلة. يشرح كيف أن كل واحد منهم قدم رؤية مختلفة بناء على فلسفته الخاصة ومعتقداته الاجتماعية والسياسية.
Book
Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination
Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (
n
= 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (
n
= 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (
n
= 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.
In healthy adults, booster vaccination with an mRNA vaccine, irrespective of the vaccine used for the first dose, was well tolerated and elicited higher levels of spike-specific antibodies and spike-specific T cells than booster vaccination with ChAdOx1 nCov-19.
Journal Article
Lost kingdoms : Hindu-Buddhist sculpture of early Southeast Asia /
\"Numerous Hindu and Buddhist kingdoms flourished in Southeast Asia from the 5th to the 9th century, yet until recently few concrete details were known about them. Lost Kingdoms reveals newly discovered architectural and sculptural relics from this region, which provide key insights into the formerly mysterious kingdoms. The first publication to use sculpture as a lens to explore this period of Southeast Asian history, Lost Kingdoms offers a significant contribution and a fresh approach to the study of cultures in Cambodia, Thailand, Burma, and other countries\"--Distributor's website.
Book
Applied machine learning as a driver for polymeric biomaterials design
Polymers are ubiquitous to almost every aspect of modern society and their use in medical products is similarly pervasive. Despite this, the diversity in commercial polymers used in medicine is stunningly low. Considerable time and resources have been extended over the years towards the development of new polymeric biomaterials which address unmet needs left by the current generation of medical-grade polymers. Machine learning (ML) presents an unprecedented opportunity in this field to bypass the need for trial-and-error synthesis, thus reducing the time and resources invested into new discoveries critical for advancing medical treatments. Current efforts pioneering applied ML in polymer design have employed combinatorial and high throughput experimental design to address data availability concerns. However, the lack of available and standardized characterization of parameters relevant to medicine, including degradation time and biocompatibility, represents a nearly insurmountable obstacle to ML-aided design of biomaterials. Herein, we identify a gap at the intersection of applied ML and biomedical polymer design, highlight current works at this junction more broadly and provide an outlook on challenges and future directions.
The design of polymers for regenerative medicine could be accelerated with the help of machine learning. Here the authors note that machine learning has been applied successfully in other areas of polymer chemistry, while highlighting that data limitations must be overcome to enable widespread adoption within polymeric biomaterials.
Journal Article
The role of mitochondria in rheumatic diseases
The mitochondrion is an intracellular organelle thought to originate from endosymbiosis between an ancestral eukaryotic cell and an α-proteobacterium. Mitochondria are the powerhouses of the cell, and can control several important processes within the cell, such as cell death. Conversely, dysregulation of mitochondria possibly contributes to the pathophysiology of several autoimmune diseases. Defects in mitochondria can be caused by mutations in the mitochondrial genome or by chronic exposure to pro-inflammatory cytokines, including type I interferons. Following the release of intact mitochondria or mitochondrial components into the cytosol or the extracellular space, the bacteria-like molecular motifs of mitochondria can elicit pro-inflammatory responses by the innate immune system. Moreover, antibodies can target mitochondria in autoimmune diseases, suggesting an interplay between the adaptive immune system and mitochondria. In this Review, we discuss the roles of mitochondria in rheumatic diseases such as systemic lupus erythematosus, antiphospholipid syndrome and rheumatoid arthritis. An understanding of the different contributions of mitochondria to distinct rheumatic diseases or manifestations could permit the development of novel therapeutic strategies and the use of mitochondria-derived biomarkers to inform pathogenesis.The mitochondrion has multiple functions, including energy production, regulation of apoptosis and reactive oxygen species generation. Disruption of these mitochondrial processes can lead to pro-inflammatory immune responses. This Review discussions the role of mitochondria and mitochondrial dysfunction in rheumatic diseases.
Journal Article
Toward the 2020 goal of soil-transmitted helminthiasis control and elimination
[...]without a strategic transition plan in place, communities that used to benefit from lymphatic filariasis control activities run the risk of undermining the gains already made for soil-transmitted helminthiasis control once GPELF is discontinued. [...]the Committee welcomes the recent approval of a new, rapidly disintegrating chewable formulation of mebendazole. [...]as for other chronic infections (e.g., tuberculosis, human immune deficiency virus [HIV], and malaria), combination therapy against soil-transmitted helminthiasis might decrease this risk and could enhance efficacy [25]. [...]the need for combination therapy is further supported by coendemicity of multiple helminth infections. [...]there is a need to develop a new survey design that (1) is sufficiently powered to assess if the prevalence of moderate- or heavy-intensity infections falls below 1% and (2) is feasible and affordable, considering the limited resources and capacity of national soil-transmitted helminthiasis control programs.
Journal Article