27 research outputs found

    Is the commercial determinants conversation confined to the health sciences? Potentially, and that’s a problem

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    The commercial determinants of health (CDoH) are attracting increased interest and are of great importance when discussing how trade affects health. Through a citation analysis of recent foundational CDoH documents (a Lancet paper series and an Oxford University textbook), we find that fully 71% of all citations reference the health sciences. The health sciences may be well suited to documenting the specific pathways of how commercial (by)products and practices harm human health. However, to operationalize upstream solutions for mitigating these harms, our citation analysis suggests that the field can engage political scientists, economists, sociologists, the trade law and business, as well as advocates in civil society and journalism, more so than it currently does. With CDoH explicitly referring to the interaction between commerce and health, CDoH researchers might be uniquely positioned to get health on the agenda of others, which requires that CDoH methods, datasets, evidence reviews, and proposed interventions are drawn from the widest possible range of sources.</p

    Track and Trace of Administrative Costs in the Dutch Long-Term Care System

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    Context: Practitioners and politicians alike emphasise the wish to reduce administrative costs (AC) in Dutch LTC, but a robust empirical body of evidence on the components, determinants and value of AC in LTC is absent. Neither has the expert consensus of ways to track and trace AC in LTC been sought. Objective(s): We investigated whether it is possible to reach consensus on operationalising AC in Dutch LTC. Successively we also explored whether the Dutch LTC reform in 2015 had the intended effect of reducing AC. Methods: We differentiated between AC for governing and financing LTC (macro), overhead costs of LTC delivery organisations (meso) and AC on the level of professional care delivery activities (micro). We identified possible data sources in grey literature and national accounts. The quality and completeness of identified data and potential determinants of AC were validated by experts via a survey and focus group discussions. Findings: We were able to reach agreement on how to track AC in Dutch LTC, but current research instruments and data systems are not robust and consistent enough to trace differences before and after the 2015 reform. Limitations: We did not investigate AC experienced by patients and self-selected participating experts. Implications: AC concern a considerable share of total LTC spending, but AC are hidden in regular health expenditure statistics. Our study highlights three approaches for a more sophisticated and fact-based policy debate on reducing low-value AC; defining AC on macro, meso and micro levels of the health care system, determining the underlying value/use of activities; and focusing on interactions of AC between system levels

    Kennisagenda samen gezond leven:Hoe dan?

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    In het begin van 2020 heeft staatssecretaris Paul Blokhuis het Kennisplatform Preventie in het leven geroepen. Dit platform bestaat uit experts uit de wetenschap, het beleid en de praktijk van preventie. Het doel is om tot meer samenhang te komen in de programmering en het gebruik van kennis over preventie, aan de hand van een dynamische kennisagenda. In haar meest recente agenda (Kennisagenda preventie 2021: mentale gezondheid op de agenda – ZonMw) stelt het kennisplatform dat hoe-vragen meer prioriteit verdienen dan wat-vragen, als het gaat om leefstijl en mentale gezondheid. Dit artikel licht de aanleiding en inhoud van de kennisagenda en het kennisplatform toe, en roept lezers op om mee te denken via [email protected]

    Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes

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    T-cell immunity in the liver is tightly regulated to prevent chronic liver inflammation in response to antigens and toxins derived from food and intestinal bacterial flora. Since the main sites of T cell activation in response to foreign components entering solid tissues are the draining lymph nodes (LN), we aimed to study whether Antigen-Presenting Cell (APC) subsets in human liver lymph-draining LN show features that may contribute to the immunologically tolerant liver environment. Healthy liver LN, iliac LN, spleen and liver perfusates were obtained from multi-organ donors, while diseased liver LN were collected from explanted patient livers. Inguinal LN were obtained from kidney transplant recipients. Mononuclear cells were isolated from fresh tissues, and immunophenotypic and functional characteristics of APC subsets were studied using flowcytometry and in ex vivo cultures. Healthy liver-draining LN contained significantly lower relative numbers of CD1c+ conventional dendritic cells (cDC2), plasmacytoid DC (PDC), and CD14+CD163+DC-SIGN+ macrophages (MF) compared to inguinal LN. Compared to spleen, both types of LN contained low relative numbers of CD141hi cDC1. Both cDC subsets in liver LN showed a more activated/mature immunophenotype than those in inguinal LN, iliacal LN, spleen and liver tissue. Despite their more mature status, cDC2 isolated from hepatic LN displayed similar cytokine production capacity (IL-10, IL-12, and IL-6) and allogeneic T cell stimulatory capacity as their counterparts from spleen. Liver LN from patients with inflammatory liver diseases showe

    Characterization of Antigen-Presenting Cell Subsets in Human Liver-Draining Lymph Nodes

    Get PDF
    T-cell immunity in the liver is tightly regulated to prevent chronic liver inflammation in response to antigens and toxins derived from food and intestinal bacterial flora. Since the main sites of T cell activation in response to foreign components entering solid tissues are the draining lymph nodes (LN), we aimed to study whether Antigen-Presenting Cell (APC) subsets in human liver lymph-draining LN show features that may contribute to the immunologically tolerant liver environment. Healthy liver LN, iliac LN, spleen and liver perfusates were obtained from multi-organ donors, while diseased liver LN were collected from explanted patient livers. Inguinal LN were obtained from kidney transplant recipients. Mononuclear cells were isolated from fresh tissues, and immunophenotypic and functional characteristics of APC subsets were studied using flowcytometry and in ex vivo cultures. Healthy liver-draining LN contained significantly lower relative numbers of CD1c+ conventional dendritic cells (cDC2), plasmacytoid DC (PDC), and CD14+CD163+DC-SIGN+ macrophages (MF) compared to inguinal LN. Compared to spleen, both types of LN contained low relative numbers of CD141hi cDC1. Both cDC subsets in liver LN showed a more activated/mature immunophenotype than those in inguinal LN, iliacal LN, spleen and liver tissue. Despite their more mature status, cDC2 isolated from hepatic LN displayed similar cytokine production capacity (IL-10, IL-12, and IL-6) and allogeneic T cell stimulatory capacity as their counterparts from spleen. Liver LN from patients with inflammatory liver diseases showed a further reduction of cDC1, but had increased relative numbers of PDC and MF. In steady state conditions human liver LN contain relatively low numbers of cDC2, PDC, and macrophages, and relative numbers of cDC1 in liver LN decline during liver inflammation. The paucity of cDC in liver LN may contribute to immune tolerance in the liver environment

    Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

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    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

    Genetic architecture of subcortical brain structures in 38,851 individuals

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    Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease
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