Microscopy with undetected photons in the mid-infrared

Owing to its capacity for unique (bio)-chemical specificity, microscopy withmid-IR illumination holds tremendous promise for a wide range of biomedical and industrial applications. The primary limitation, however, remains detection; with current mid-IR detection technology often marrying inferior technical capabilities with prohibitive costs. This has lead to approaches that shift detection towavelengths into the visible regime, where vastly superior silicon-based cameratechnology is available. Here, we experimentally show how nonlinear interferometry with entangled light can provide a powerful tool for mid-IR microscopy, while only requiring near-infrared detection with a standard CMOS camera. In this proof-of-principle implementation, we demonstrate intensity imaging overa broad wavelength range covering 3.4-4.3um and demonstrate a spatial resolution of 35um for images containing 650 resolved elements. Moreover, we demonstrate our technique is fit for purpose, acquiring microscopic images of biological tissue samples in the mid-IR. These results open a new perspective for potential relevance of quantum imaging techniques in the life sciences.Comment: back-to-back submission with arXiv:2002.05956, Anna V. Paterova, Sivakumar M. Maniam, Hongzhi Yang, Gianluca Grenci, and Leonid A. Krivitsky, "Hyperspectral Infrared Microscopy With Visible Light

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

The value of trauma center care

BACKGROUND: The cost of trauma center care is high, raising questions about the value of a regionalized approach to trauma care. To address these concerns, we estimate 1-year and lifetime treatment costs and measure the cost-effectiveness of treatment at a Level I trauma center (TC) compared with a nontrauma center hospital (NTC). METHODS: Estimates of cost-effectiveness were derived using data on 5,043 major trauma patients enrolled in the National Study on Costs and Outcomes of Trauma, a prospective cohort study of severely injured adult patients cared for in 69 hospitals in 14 states. Data on costs were derived from multiple sources including claims data from the Centers for Medicare and Medicaid Services, UB92 hospital bills, and patient interviews. Cost-effectiveness was estimated as the ratio of the difference in costs (for treatment at a TC vs. NTC) divided by the difference in life years gained (and lives saved). We also measured cost-effectiveness per quality-adjusted life year gained where quality of life was measured using the SF-6D. We used inverse probability of treatment weighting to adjust for observable differences between patients treated at TCs and NTCs. RESULTS: The added cost for treatment at a TC versus NTC was $36,319 per life-year gained ($790,931 per life saved) and $36,961 per quality-adjusted life years gained. Cost-effectiveness was more favorable for patients with injuries of higher versus lower severity and for younger versus older patients. CONCLUSIONS: Our findings provide evidence that regionalization of trauma care is not only effective but also it is cost-effective

The National Study on Costs and Outcomes of Trauma

The National Study on the Costs and Outcomes of Trauma Care (NSCOT) was designed to address the need for better information on the value of trauma center care. It is a multi-institutional, prospective study that involved the examination of costs and outcomes of care received by over 5,000 adult trauma patients 18 to 84 years of age treated at 69 hospitals located in 12 states. The study had three major objectives: (1) to examine variations in care provided to trauma patients in Level I trauma centers and nontrauma center hospitals; (2) to determine the extent to which differences in care correlate with patient outcome, where outcome is defined not just in terms of mortality and morbidity, but also in terms of major functional outcomes at 3 months and 12 months after injury; and (3) to estimate acute and 1-year treatment costs for trauma center and nontrauma center care, and to describe the relationship between costs and effectiveness for trauma centers and nontrauma centers. In this article, we describe the design of the NSCOT study and point to some of the methodological challenges faced in its implementation and in the analysis of the data. We also present a description of the study population to serve as a basis of future reports. We conclude with lessons learned and some recommendations for future research