Notes

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56, 95% CI 1.31, 1.87) and functional limitations (OR 1.55, 95% CI 1.29, 1.87). However, race moderated the impact of discrimination on functional limitations for Blacks. Finally, a strong sense of belonging to one's local community was protective against pain and functional limitations for all racial groups.

Future research needs to further examine the impact of discrimination on Indigenous peoples' aging process. High rates of discrimination coupled with a greater burden of pain means that Indigenous midlife and older adults may require additional and targeted health and social service resources to age successfully.
Future research needs to further examine the impact of discrimination on Indigenous peoples' aging process. High rates of discrimination coupled with a greater burden of pain means that Indigenous midlife and older adults may require additional and targeted health and social service resources to age successfully.Advances in cancer research have led to the development of new therapeutics with significant and durable responses such as immune checkpoint inhibitors. More recent therapies aim to stimulate anti-tumor immune responses by targeting the tumor necrosis factor (TNF) receptors, however this approach has been shown to require clustering of receptors in order to achieve a significant response. Here we present a perspective on using transthyretin, a naturally occurring serum protein, as a drug delivery platform to enable cross-linking independent clustering of targets. TTR forms a stable homo-tetramer with exposed termini that make TTR a highly versatile platform for generating multimeric antibody fusions to enable enhanced target clustering. Fusions with antibodies or Fabs targeting TRAILR2 were shown to have robust cytotoxic activity in vitro and in vivo in colorectal xenograft models demonstrating that TTR is a highly versatile, stable, therapeutic fusion platform that can be used with antibodies, Fabs and other bioactive fusion partners and has broad applications in oncology and infectious disease research.Dolutegravir-based regimens are now standard of care for HIV treatment for millions of people around Sub-Saharan Africa. To ensure its continued efficacy, monitoring of emerging drug resistance that inform a treatment strategy amongst those failing is crucial. Masitinib purchase Here we outline the plan by the President Emergence Plan for AIDS Relief to leverage viral load infra structure to implement effective drug resistance surveillance in the countries it supports.Microglia are highly dynamic cells crucial for developing and maintaining lifelong brain function and health through their many interactions with essentially all cellular components of the central nervous system. The frequent connection of microglia to leukodystrophies, genetic disorders of the white matter, has highlighted their involvement in the maintenance of white matter integrity. However, the mechanisms that underlie their putative roles in these processes remain largely uncharacterized. Microglia have also been gaining attention as possible therapeutic targets for many neurological conditions, increasing the demand to understand their broad spectrum of functions and the impact of their dysregulation. In this Review, we compare the pathological features of two groups of genetic leukodystrophies those in which microglial dysfunction holds a central role, termed 'microgliopathies', and those in which lysosomal or peroxisomal defects are considered to be the primary driver. The latter are suspected to have notable microglia involvement, as some affected individuals benefit from microglia-replenishing therapy. Based on overlapping pathology, we discuss multiple ways through which aberrant microglia could lead to white matter defects and brain dysfunction. We propose that the study of leukodystrophies, and their extensively multicellular pathology, will benefit from complementing analyses of human patient material with the examination of cellular dynamics in vivo using animal models, such as zebrafish. Together, this will yield important insight into the cell biological mechanisms of microglial impact in the central nervous system, particularly in the development and maintenance of myelin, that will facilitate the development of new, and refinement of existing, therapeutic options for a range of brain diseases.Situated models of emotion hypothesize that emotions are optimized for the context at hand, but most neuroimaging approaches ignore context. For the first time, we applied Granger causality (GC) analysis to determine how an emotion is affected by a person's cultural background and situation. Electroencephalographic (EEG) recordings were taken from mainland Chinese and US participants as they viewed and rated fearful and neutral images displaying either social or non-social contexts. Independent components analysis (ICA) and GC analysis was applied to determine the epoch of peak effect for each condition and to identify sources and sinks among brain regions of interest. We found that source-sink couplings differed across culture, situation, and culture x situation. Mainland Chinese participants alone showed preference for an early-onset source-sink pairing with the supramarginal gyrus as a causal source, suggesting that, relative to US participants, Chinese participants more strongly prioritized a scene's social aspects in their response to fearful scenes. Our findings suggest that the neural representation of fear indeed varies according to both culture, situation, and their interaction in ways that are consistent with norms instilled by cultural background.
While single indicators measure a specific aspect of quality (e.g. timely support during labour), users of these indicators, such as patients, providers and policy-makers, are typically interested in some broader construct (e.g. quality of maternity care) whose measurement requires a set of indicators. However, guidance on desirable properties of indicator sets is lacking.

Based on the premise that a set of valid indicators does not guarantee a valid set of indicators, the aim of this review is 2-fold First, we introduce content validity as a desirable property of indicator sets and review the extent to which studies in the peer-reviewed health care quality literature address this criterion. Second, to obtain a complete inventory of criteria, we examine what additional criteria of quality indicator sets were used so far.

We searched the databases Web of Science, Medline, Cinahl and PsycInfo from inception to May 2021 and the reference lists of included studies. English- or German-language, peer-reviewed studies concerned with desirable characteristics of quality indicator sets were included.
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