The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig

New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion

Transcriptional profiling of eosinophil subsets in interleukin-5 transgenic mice

Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL-5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL-5 have in excess of 10-fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in WT mice. In this study, we assessed transcription in myeloid progenitors, eosinophil precursors, and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilized these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend toward quiescence along the trajectory. Additionally, we found gene expression changes associated with constitutive IL-5 signaling in eosinophil progenitors, many of which were not observed in eosinophils

Measuring global trends in the status of biodiversity: red list indices for birds.

The rapid destruction of the planet's biodiversity has prompted the nations of the world to set a target of achieving a significant reduction in the rate of loss of biodiversity by 2010. However, we do not yet have an adequate way of monitoring progress towards achieving this target. Here we present a method for producing indices based on the IUCN Red List to chart the overall threat status (projected relative extinction risk) of all the world's bird species from 1988 to 2004. Red List Indices (RLIs) are based on the number of species in each Red List category, and on the number changing categories between assessments as a result of genuine improvement or deterioration in status. The RLI for all bird species shows that their overall threat status has continued to deteriorate since 1988. Disaggregated indices show that deteriorations have occurred worldwide and in all major ecosystems, but with particularly steep declines in the indices for Indo-Malayan birds (driven by intensifying deforestation of the Sundaic lowlands) and for albatrosses and petrels (driven by incidental mortality in commercial longline fisheries). RLIs complement indicators based on species population trends and habitat extent for quantifying global trends in the status of biodiversity. Their main weaknesses are that the resolution of status changes is fairly coarse and that delays may occur before some status changes are detected. Their greatest strength is that they are based on information from nearly all species in a taxonomic group worldwide, rather than a potentially biased subset. At present, suitable data are only available for birds, but indices for other taxonomic groups are in development, as is a sampled index based on a stratified sample from all major taxonomic groups

The epidemiology of kidney disease in people of African ancestry with HIV in the UK

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality globally. The risk of CKD is increased in people of African ancestry and with Human Immunodeficiency Virus (HIV) infection. Methods: We conducted a cross-sectional study investigating the relationship between region of ancestry (East, Central, South or West Africa) and kidney disease in people of sub-Saharan African ancestry with HIV in the UK between May 2018 and February 2020. The primary outcome was renal impairment (estimated glomerular filtration rate [eGFR] of 50 mg/mmol), and biopsy-confirmed HIV-associated nephropathy (HIVAN), focal segmental glomerulosclerosis (FSGS) or arterionephrosclerosis. Multivariable robust Poisson regression estimated the effect of region of African ancestry on kidney disease outcomes. Findings: Of the 2468 participants (mean age 48.1 [SD 9.8] years, 62% female), 193 had renal impairment, 87 stage 5 CKD, 126 proteinuria, and 43 HIVAN/FSGS or arterionephrosclerosis. After adjusting for demographic characteristics, HIV and several CKD risk factors and with East African ancestry as referent, West African ancestry was associated with renal impairment (prevalence ratio [PR] 2.06 [95% CI 1.40–3.04]) and stage 5 CKD (PR 2.23 [1.23–4.04]), but not with proteinuria (PR 1.27 [0.78–2.05]). West African ancestry (as compared to East/South African ancestry) was also strongly associated with a diagnosis of HIVAN/FSGS or arterionephrosclerosis on kidney biopsy (PR 6.44 [2.42–17.14]). Interpretation: Our results indicate that people of West African ancestry with HIV are at increased risk of kidney disease. Although we cannot rule out the possibility of residual confounding, geographical region of origin appears to be a strong independent risk factor for CKD as the association did not appear to be explained by several demographic, HIV or renal risk factors

The first legal mortgagor: a consumer without adequate protection?

This article contends that the UK government’s attempt to create a well-functioning consumer credit market will be undermined if it fails to reform the private law framework relating to the first legal mortgage. Such agreements are governed by two distinct regulatory regimes that are founded upon very different conceptions of the mortgagor. The first, the regulation of financial services overseen by the Financial Conduct Authority, derives from public law and is founded upon a conception of the mortgagor as “consumer”. The other is land law, private law regulation implemented by the judiciary and underpinned by a conception of the mortgagor as “landowner”. Evidence suggests that the operation of these two regimes prevents mortgagors from receiving fair and consistent treatment. The current reform of financial services regulation therefore will change only one part of this governance regime and will leave mortgagors heavily reliant upon a regulator that still has to prove itself. What this article argues is that reform of the rules of private law must also be undertaken with the aim of initiating a paradigm shift in the conception of the mortgagor from “landowner” to “consumer”. Cultural shifts of this kind take time but the hope is that this conceptual transformation will occur in time to deter the predicted rise in mortgage possessions

Utilisation and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study.

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilisation, survival, and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥ 2 + on dipstick testing, on kidney utilisation, early graft function, graft failure, and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen % (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% vs 82%; OR 0.70, 95% CI 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (HR 0.91, 95% CI 0.74 to 1.11). There was also no association with delayed graft function, patient survival, or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilise kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilisation without negatively impacting transplant outcomes

Primary care nurses' experiences of how the mass media influence frontline healthcare in the UK

Background: Mass media plays an important role in communicating about health research and services to patients, and in shaping public perceptions and decisions about health. Healthcare professionals also play an important role in providing patients with credible, evidence-based and up-to-date information on a wide range of health issues. This study aims to explore primary care nurses' experiences of how mass media influences frontline healthcare.<p></p> Methods: In-depth telephone interviews were carried out with 18 primary care nurses (nine health visitors and nine practice nurses) working in the United Kingdom (UK). Interviews were recorded and transcribed. The data was analysed using thematic analysis, with a focus on constant comparative analysis.<p></p> Results: Three themes emerged from the data. First, participants reported that their patients were frequently influenced by controversial health stories reported in the media, which affected their perceptions of, and decisions about, care. This, in turn, impinged upon participants' workloads as they had to spend additional time discussing information and reassuring patients. Second, participants also recalled times in their own careers when media reports had contributed to a decline in their confidence in current healthcare practices and treatments. Third, the participants in this study suggested a real need for additional resources to support and expand their own media literacy skills, which could be shared with patients.<p></p> Conclusion: In an ever expanding media landscape with greater reporting on health, nurses working in the primary care setting face increasing pressure to effectively manage media stories that dispute current health policies and practices. These primary care nurses were keen to expand their media literacy skills to develop critical autonomy in relation to all media, and to facilitate more meaningful conversations with their patients about their health concerns and choices.<p></p&gt

The 24-h Energy Intake of Obese Adolescents Is Spontaneously Reduced after Intensive Exercise: A Randomized Controlled Trial in Calorimetric Chambers

Background: Physical exercise can modify subsequent energy intake and appetite and may thus be of particular interest in terms of obesity treatment. However, it is still unclear whether an intensive bout of exercise can affect the energy consumption of obese children and adolescents. [br/] Objective: To compare the impact of high vs. moderate intensity exercises on subsequent 24-h energy intake, macronutrient preferences, appetite sensations, energy expenditure and balance in obese adolescent. [br/] Design: This randomized cross-over trial involves 15 obese adolescent boys who were asked to randomly complete three 24-h sessions in a metabolic chamber, each separated by at least 7 days: (1) sedentary (SED); (2) Low-Intensity Exercise (LIE) (40% maximal oxygen uptake, VO(2)max); (3) High-Intensity Exercise (HIE) (75% VO(2)max). Results: Despite unchanged appetite sensations, 24-h total energy intake following HIE was 6-11% lower compared to LIE and SED (p<0.05), whereas no differences appeared between SED and LIE. Energy intake at lunch was 9.4% and 8.4% lower after HIE compared to SED and LIE, respectively (p<0.05). At dinner time, it was 20.5% and 19.7% lower after HIE compared to SED and LIE, respectively (p<0.01). 24-h energy expenditure was not significantly altered. Thus, the 24-h energy balance was significantly reduced during HIE compared to SED and LIE (p<0.01), whereas those of SED and LIE did not differ. [br/] Conclusions: In obese adolescent boys, HIE has a beneficial impact on 24-h energy balance, mainly due to the spontaneous decrease in energy intake during lunch and dinner following the exercise bout. Prescribing high-intensity exercises to promote weight loss may therefore provide effective results without affecting appetite sensations and, as a result, food frustrations