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Previous observational studies suggested that vitamin D may control the absorption of iron (Fe) by inhibition of hepcidin, but the causal relevance of these associations is uncertain. Using placebo-controlled randomisation, we assessed the effects of supplementation with vitamin D on biochemical markers of Fe status and erythropoiesis in community-dwelling older people living in the UK. The BEST-D trial, designed to establish the optimum dose of vitamin D3 for future trials, had 305 participants, aged 65 years or older, randomly allocated to 4000 IU vitamin D3 (n 102), 2000 IU vitamin D3 (n 102) or matching placebo (n 101). We estimated the effect of vitamin D allocation on plasma levels of hepcidin, soluble transferrin receptor (sTfR), ferritin, Fe, transferrin, saturated transferrin (TSAT%) and the sTfR–ferritin index. Despite increases in 25-hydroxy-vitamin D, neither dose had significant effects on biochemical markers of Fe status or erythropoiesis. Geometric mean concentrations were similar in vitamin D3 arms v. placebo for hepcidin (20·7 [se 0·90] v. 20·5 [1·21] ng/ml), sTfR (0·69 [0·010] v. 0·70 [0·015] µg/ml), ferritin (97·1 [2·81] v. 97·8 [4·10] µg/l) and sTfR–ferritin ratio (0·36 [0·006] v. 0·36 [0·009]), respectively, while arithmetic mean levels were similar for Fe (16·7 [0·38] v. 17·3 [0·54] µmol/l), transferrin (2·56 [0·014] v. 2·60 [0·021] g/dl) and TSAT% (26·5 [0·60] v. 27·5 [0·85]). The proportions of participants with ferritin < 15 µg/l and TSAT < 16 % were unaltered by vitamin D3 suggesting that 12 months of daily supplementation with moderately high doses of vitamin D3 are unlikely to alter the Fe status of older adults.
This comprehensive text focuses on the homotopical technology in use at the forefront of modern algebraic topology. Following on from a standard introductory algebraic topology sequence, it will provide students with a comprehensive background in spectra and structured ring spectra. Each chapter is an extended tutorial by a leader in the field, offering the first really accessible treatment of the modern construction of the stable category in terms of both model categories of point-set diagram spectra and infinity-categories. It is one of the only textbook sources for operadic algebras, structured ring spectra, and Bousfield localization, which are now basic techniques in the field, and the book provides a rare expository treatment of spectral algebraic geometry. Together the contributors — Emily Riehl, Daniel Dugger, Clark Barwick, Michael A. Mandell, Birgit Richter, Tyler Lawson, and Charles Rezk — offer a complete, authoritative source to learn the foundations of this vibrant area.
Illness and mortality have social origins, and infants and children are especially susceptible to the impacts of adverse social experiences. Early-life stress (ELS) – physiological disruptions suffered by a developing organism – is incorporated into human biology through embodiment. This paper examines whether children who lived and died in New Mexico (2011–2019) embodied social determinants of health. Data were collected from 780 postmortem computed tomography scans in conjunction with data from field notes and autopsy reports for individuals aged 0.5–20.99 years from New Mexico. Variables included in linear/logistic regressions are the per cent of families in poverty by ZIP code and year, housing type (trailer/mobile home, apartment, house), rural/urban residence areas, and race/ethnicity. Health outcome variables are age at death, respiratory conditions, growth stunting and arrest, and porous cranial lesions. Intersections of poverty, housing disparities, and race/ethnicity are examined to understand whether children from New Mexico incorporated ELS into their biology.
Results
Hispanic children have higher odds of growth stunting than non-Hispanic White children. Native American children die younger and have higher odds of respiratory diseases and porous lesions than Hispanic and non-Hispanic Whites. Rural/urban location does not significantly impact age at death, but housing type does. Individuals who lived in trailers/mobile homes had earlier ages at death. When intersections between housing type and housing location are considered, children who were poor and from impoverished areas lived longer than those who were poor from relatively well-off areas.
Conclusions
Children’s health is shaped by factors outside their control. The children included in this study embodied experiences of social and ELS and did not survive to adulthood. They provide the most sobering example of the harm that social factors (structural racism/discrimination, socioeconomic, and political structures) can inflict.
To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a “real-world” setting.
Methods:
Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a “real-world” setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY.
Results:
Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%–99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%–61.6%), but not the “real-world” setting (acceptability:32.9%–42.6%).
Conclusion:
EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and “real-world” setting, although this was largely related to baseline patient differences favoring the “real-world” EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.
Policies to decrease low-acuity emergency department (ED) use have traditionally assumed that EDs are a substitute for unavailable primary care (PC). However, such policies can exacerbate ED overcrowding, rather than ameliorate it, if patients use EDs to complement, rather than substitute, their PC use. We tested whether Medicaid managed care enrolees visit the ED for nonemergent and PC treatable conditions to substitute for or to complement PC. Based on consumer choice theory, we modelled county-level monthly ED visit rate as a function of PC supply and used 2012–2015 New York Statewide Planning and Research Cooperative System (SPARCS) outpatient data and non-linear least squares method to test substitution vs complementarity. In the post-Medicaid expansion period (2014–2015), ED and PC are substitutes state-wide, but are complements in highly urban and poorer counties during nights and weekends. There is no evidence of complementarity before the expansion (2012–2013). Analyses by PC provider demonstrate that the relationship between ED and PC differs depending on whether PC is provided by physicians or advanced practice providers. Policies to reduce low-acuity ED use via improved PC access in Medicaid are likely to be most effective if they focus on increasing actual appointment availability, ideally by physicians, in areas with low PC provider supply. Different aspects of PC access may be differently related to low-acuity ED use.
Monitoring parrot populations is of high importance because there is a general lack of quantified population trends for one of the most threatened avian orders. We surveyed parrots in Nicaragua in 1995, 1999, 2004, and 2013 at a minimum of 227 points within 56 sites stratified among the Pacific, Central Highlands, and Caribbean biogeographical regions to assess population trends. From point-count data we calculated encounter rate, flock rate, and flock size metrics and we used presence/absence data to generate species-specific occupancy estimates. Encounter rate, flock rate, and flock size data suggested family-level declines from 1995 to 2004 with some recovery between 2004 and 2013. Patterns of parrot occupancy varied among species with four decreasing, five increasing, and two with no detectable change. Six species of conservation concern are identified, including the Critically Endangered Great Green Macaw and Yellow-naped Parrot, additionally Olive-throated Parakeet, Scarlet Macaw, Brown-hooded Parrot, and White-crowned Parrot, only listed as Least Concern. All six are likely suffering from deforestation and potential unchecked trade activity in the Caribbean. Differing population trends of the regionally disjunct Yellow-naped Parrot subspecies suggest a link to variable deforestation and trade pressure experienced between the Pacific and Caribbean. Our results highlight the importance of actively monitoring changing parrot populations, even when considered Least Concern, so that directed conservation actions can be taken if needed.
The modern era in homotopy theory began in the 1960s with the profound realization, first codified by Boardman in his construction of the stable category, that the category of spaces up to stable homotopy equivalence is equipped with a rich algebraic structure, formally similar to the derived category of a commutative ring R. For example, for pointed spaces the natural map from the categorical coproduct to the categorical product becomes more and more connected as the pieces themselves become more and more connected. In the limit, this map becomes a stable equivalence, just as finitely indexed direct sums and direct products coincide for R-modules.
From this perspective, the objects of the stable category are modules over an initial commutative ring object that replaces the integers: the sphere spectrum. However, technical difficulties immediately arose. Whereas the tensor product of R-modules is an easy and familiar construction, the analogous construction of a symmetric monoidal smash product on spectra seemed to involve a huge number of ad hoc choices [1]. As a consequence, the smash product was associative and commutative only up to homotopy. The lack of a good point-set symmetric monoidal product on spectra precluded making full use of the constructions from commutative algebra in this setting — even just defining good categories of modules over a commutative ring spectrum was difficult. In many ways, finding ways to rectify this and to make the guiding metaphor provided by “modules over the sphere spectrum” precise has shaped the last 60 years of homotopy theory.
This book arose from a desire by the editors to have a reference to give to their students who have taken a standard algebraic topology sequence and who want to learn about spectra and structured ring spectra. While there are many excellent texts which introduce students to the basic ideas of homotopy theory and to spectra, there has not been a place for students to engage directly with the ideas needed to connect with commutative ring spectra and work with these objects. This book strives to provide an introduction to this whole circle of ideas, describing the tools that homotopy theorists have developed to build, explore, and use symmetric monoidal categories of spectra that refine the stable homotopy category:
1. model category structures on symmetric monoidal categories of spectra,
2. stable ∞-categories, and
3. operads and operadic algebras.
These three concepts are closely intertwined, and they all engage deeply with a fundamental principle: if the choices for some construction or map are parameterized by a space, then recording that space as part of the data makes the construction more natural.
Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED).
Design:
We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm.
Setting:
Emergency department of a university teaching hospital.
Patients:
Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a ‘high-risk’ area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area.
Results:
Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34–92) for FebriDx-negative patients and 203 minutes (IQR, 142–255) for FebriDx-positive patients (difference of −134 minutes; 95% CI, −144 to −122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%–97%).
Conclusions:
FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2–positive patients.
Paramedics received training in point-of-care ultrasound (POCUS) to assess for cardiac contractility during management of medical out-of-hospital cardiac arrest (OHCA). The primary outcome was the percentage of adequate POCUS video acquisition and accurate video interpretation during OHCA resuscitations. Secondary outcomes included POCUS impact on patient management and resuscitation protocol adherence.
Methods:
A prospective, observational cohort study of paramedics was performed following a four-hour training session, which included a didactic lecture and hands-on POCUS instruction. The Prehospital Echocardiogram in Cardiac Arrest (PECA) protocol was developed and integrated into the resuscitation algorithm for medical non-shockable OHCA. The ultrasound (US) images were reviewed by a single POCUS expert investigator to determine the adequacy of the POCUS video acquisition and accuracy of the video interpretation. Change in patient management and resuscitation protocol adherence data, including end-tidal carbon dioxide (EtCO2) monitoring following advanced airway placement, adrenaline administration, and compression pauses under ten seconds, were queried from the prehospital electronic health record (EHR).
Results:
Captured images were deemed adequate in 42/49 (85.7%) scans and paramedic interpretation of sonography was accurate in 43/49 (87.7%) scans. The POCUS results altered patient management in 14/49 (28.6%) cases. Paramedics adhered to EtCO2 monitoring in 36/36 (100.0%) patients with an advanced airway, adrenaline administration for 38/38 (100.0%) patients, and compression pauses under ten seconds for 36/38 (94.7%) patients.
Conclusion:
Paramedics were able to accurately obtain and interpret cardiac POCUS videos during medical OHCA while adhering to a resuscitation protocol. These findings suggest that POCUS can be effectively integrated into paramedic protocols for medical OHCA.