Ly6Chi monocyte recruitment is responsible for Th2 associated host-protective macrophage accumulation in liver inflammation due to schistosomiasis

Accumulation of M2 macrophages in the liver, within the context of a strong Th2 response, is a hallmark of infection with the parasitic helminth, Schistosoma mansoni, but the origin of these cells is unclear. To explore this, we examined the relatedness of macrophages to monocytes in this setting. Our data show that both monocyte-derived and resident macrophages are engaged in the response to infection. Infection caused CCR2-dependent increases in numbers of Ly6Chi monocytes in blood and liver and of CX3CR1+ macrophages in diseased liver. Ly6Chi monocytes recovered from liver had the potential to differentiate into macrophages when cultured with M-CSF. Using pulse chase BrdU labeling, we found that most hepatic macrophages in infected mice arose from monocytes. Consistent with this, deletion of monocytes led to the loss of a subpopulation of hepatic CD11chi macrophages that was present in infected but not naïve mice. This was accompanied by a reduction in the size of egg-associated granulomas and significantly exacerbated disease. In addition to the involvement of monocytes and monocyte-derived macrophages in hepatic inflammation due to infection, we observed increased incorporation of BrdU and expression of Ki67 and MHC II in resident macrophages, indicating that these cells are participating in the response. Expression of both M2 and M1 marker genes was increased in liver from infected vs. naive mice. The M2 fingerprint in the liver was not accounted for by a single cell type, but rather reflected expression of M2 genes by various cells including macrophages, neutrophils, eosinophils and monocytes. Our data point to monocyte recruitment as the dominant process for increasing macrophage cell numbers in the liver during schistosomiasis

Regulation of learning and memory by meningeal immunity: a key role for IL-4

Proinflammatory cytokines have been shown to impair cognition; consequently, immune activity in the central nervous system was considered detrimental to cognitive function. Unexpectedly, however, T cells were recently shown to support learning and memory, though the underlying mechanism was unclear. We show that one of the steps in the cascade of T cell–based support of learning and memory takes place in the meningeal spaces. Performance of cognitive tasks led to accumulation of IL-4–producing T cells in the meninges. Depletion of T cells from meningeal spaces skewed meningeal myeloid cells toward a proinflammatory phenotype. T cell–derived IL-4 was critical, as IL-4−/− mice exhibited a skewed proinflammatory meningeal myeloid cell phenotype and cognitive deficits. Transplantation of IL-4−/− bone marrow into irradiated wild-type recipients also resulted in cognitive impairment and proinflammatory skew. Moreover, adoptive transfer of T cells from wild-type into IL-4−/− mice reversed cognitive impairment and attenuated the proinflammatory character of meningeal myeloid cells. Our results point to a critical role for T cell–derived IL-4 in the regulation of cognitive function through meningeal myeloid cell phenotype and brain-derived neurotrophic factor expression. These findings might lead to the development of new immune-based therapies for cognitive impairment associated with immune decline

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Women’s Empowerment in Agriculture Index (WEAI) Pilot for Uganda

The Women’s Empowerment in Agriculture Index (WEAI) is a composite measurement tool that indicates women’s control over critical parts of their lives in the household, community, and economy. It allows us to identify women who are disempowered and understand how to increase autonomy and decisionmaking in key domains. The WEAI is also a useful tool for tracking progress toward gender equality, which is one of the Millennium Development Goals. The WEAI measures the empowerment, agency, and inclusion of women in the agriculture sector in an effort to identify ways to overcome those obstacles and constraints. The Index is a significant innovation in its field and aims to increase understanding of the connections between women’s empowerment, food security, and agricultural growth. The Uganda pilot covered five spatially dispersed rural districts in the northern region (Amuru and Kole), central region (Luwero and Masaka), and eastern region (Iganga).</br

Women’s Empowerment in Agriculture Index (WEAI) Pilot for Guatemala

The Women’s Empowerment in Agriculture Index (WEAI) is a composite measurement tool that indicates women’s control over critical parts of their lives in the household, community, and economy. It allows us to identify women who are disempowered and understand how to increase autonomy and decisionmaking in key domains. The WEAI is also a useful tool for tracking progress toward gender equality, which is one of the Millennium Development Goals. The WEAI measures the empowerment, agenc y, and inclusion of women in the agriculture sector in an effort to identify ways to overcome those obstacles and constraints. The Index is a significant innovation in its field and aims to increase understanding of the connections between women’s empowerment, food security, and agricultural growth. The Guatemala pilot was conducted in the country’s Western Highlands, in the departamentos (departments) of El Quiché, Huehuetenango, Quetzaltengo, San Marcos, and Totonicapán—areas with a high concentration of indigenous populations.</br

Women’s Empowerment in Agriculture Index (WEAI) Pilot for Bangladesh

The Women’s Empowerment in Agriculture Index (WEAI) is a composite measurement tool that indicates women’s control over critical parts of their lives in the household, community, and economy. It allows us to identify women who are disempowered and understand how to increase autonomy and decisionmaking in key domains. The WEAI is also a useful tool for tracking progress toward gender equality, which is one of the Millennium Development Goals. The WEAI measures the empowerment, agency, and inclusion of women in the agriculture sector in an effort to identify ways to overcome those obstacles and constraints. The Index is a significant innovation in its field and aims to increase understanding of the connections between women’s empowerment, food security, and agricultural growth. The Bangladesh pilot was conducted in the south and south western regions of the country, close to the Indian border, in these districts: Barguna, Jessore, Khulna, Madaripur, and Patuakhali.</br

Pilot Study: Combining Formal and Peer Education with FibroScan to Increase HCV Screening and Treatment in Persons who use Drugs

Background: Treatment uptake for hepatitis C virus (HCV) infection remains low in persons who inject drugs (PWID), due to lack of knowledge and low perceived need for treatment. Therefore, we conducted a pilot study to assess the influence on knowledge and willingness for HCV screening and treatment among persons who use drugs (PWUD) by combining formal and peer education with FibroScan measurement. Methods: Clients of the Center for Alcohol and other Drug problems (CAD) in Limburg (Belgium) were randomized into a control group, which received the standard of care, and an intervention group, which received an innovative combination of formal and peer education followed by FibroScan. Knowledge of HCV infection and willingness for screening and treatment were evaluated at baseline, after intervention and 1 and 3 months after intervention by means of questionnaires. Results: Baseline knowledge was similar for the control (n = 27) and the intervention group (n = 25) (58 vs. 59%; p = 0.67). Immediately after the information session, knowledge increased to 86% (p &lt;0.001) in the intervention group. After 3 months, knowledge decreased significantly (69%; p = 0.01). No significant changes in knowledge were found in the control group. Baseline willingness for treatment was 81% in both the control and intervention groups, but after 1 month decreased in the control group (44%) and remained stable in the intervention group (75%). Differences in actual screening uptake between the control and intervention group were not significant (7% vs. 20%). Four percent of the intervention group and no one in the control group started treatment. Conclusion: The small. number of subjects should be considered when interpreting the results of this study. In brief, the single information session significantly improved HCV knowledge among PWUD, but did not result in a higher uptake for screening and treatment. This could signify that there are other important reasons, besides lack of knowledge, not to undergo screening or start treatment. The fact that knowledge decreased after 3 months indicates that it would be beneficial to repeat the information session regularly