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Mechanical overload of the vascular wall is a pathological hallmark of life-threatening abdominal aortic aneurysms (AAA). However, how this mechanical stress resonates at the unicellular level of vascular smooth muscle cells (VSMC) is undefined. Here we show defective mechano-phenotype signatures of VSMC in AAA measured with ultrasound tweezers-based micromechanical system and single-cell RNA sequencing technique. Theoretical modelling predicts that cytoskeleton alterations fuel cell membrane tension of VSMC, thereby modulating their mechanoallostatic responses which are validated by live micromechanical measurements. Mechanistically, VSMC gradually adopt a mechanically solid-like state by upregulating cytoskeleton crosslinker, α-actinin2, in the presence of AAA-promoting signal, Netrin-1, thereby directly powering the activity of mechanosensory ion channel Piezo1. Inhibition of Piezo1 prevents mice from developing AAA by alleviating pathological vascular remodeling. Our findings demonstrate that deviations of mechanosensation behaviors of VSMC is detrimental for AAA and identifies Piezo1 as a novel culprit of mechanically fatigued aorta in AAA. Mechanobiological signals have been reported to contribute to abdominal aortic aneurysm (AAA) development. Here the authors report that the microskeletal stiffness and a Piezo1-mediated mechanism influence vascular smooth muscle cell mechanosensation and AAA disease development.

New York City was one of the epicenters of the COVID-19 pandemic. The management of peripheral artery disease (PAD) during this time has been a major challenge for health care systems and medical personnel. This document is based on the experiences of experts from various medical fields involved in the treatment of patients with PAD practicing in hospitals across New York City during the outbreak. The recommendations are based on certain aspects including the COVID-19 infection status as well as the clinical PAD presentation of the patient. Our case-based algorithm aims at guiding the treatment of patients with PAD during the pandemic in a safe and efficient way.

The rise of machine learning has revolutionised finance. Institutions across the world have increasingly turned to data science and machine learning to create trading models without the need for human intervention. This has had various implications for the financial markets that they operate in, including market efficiency. This paper simulates a financial market with agent-based modelling and Monte-Carlo style simulations, to motivate a qualitative discussion about the implications of increased algorithmic trading on financial market efficiency. It finds that algorithmic traders (ATs) can seemingly increase market efficiency through better liquidity management and more complete extraction of information from prices. However, this also comes with increased instability and potential convergence to an unstable equilibrium. The Adaptive Market Hypothesis (Lo, 2004) is suggested as an alternative framework for analysing AT behaviour.

BackgroundThe falling percentage of doctors of medicine applying for National Institute of Health-funded research grants is 1 indicator that physician-scientists are a disappearing breed. This is occurring at a time when increased translational, disease-oriented, patient-oriented, and clinical research are national goals. One of the keys to providing sufficient numbers of physician-scientists to support this goal is the active targeting of medical students. We hypothesize that an improved research program infrastructure and responsiveness to changing student needs will increase student participation in research-oriented electives.MethodsWe have developed a student research program consisting of 2 Students Interested in Research noncredit electives (lecture and laboratory based), summer fellowships, support for year-out fellowships, and a Distinction in Research program that spans undergraduate medical education. Student participation and short-term research outcomes from fall 2004 through spring 2008 are analyzed to examine program efficacy.ResultsStudents involved in the early parts of the program initially experienced higher application and success rates for summer funding opportunities, but as the program has matured, these rates have fallen in line with the class average. Independently, students participating in later portions of the program increasingly submit or publish a first author paper and have taken a year off for research during medical school. Overlap of participation in the programs is generally smaller than expected.ConclusionAlthough structured programs can provide step-wise research experiences of increasing intensity, students may not experience a training pipeline in which each stage relies on those before and after, and instead may sample an a la carte selection of research-based enrichment opportunities.

This chapter contains sections titled: Methods for endovascular graft repair Surveillance considerations for isolated iliac aneurysms treated endovascularly Conclusions References

BackgroundThere is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain.ObjectiveWe performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19.MethodsTwo reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach.ResultsWe reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66–1.46], time to fever resolution (mean difference − 0.54 days (− 1.19–011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47–1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes.Authors’ ConclusionThe available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.

Out-of-pocket (OOP) expenditure on health care has significant implications for poverty in many developing countries. This paper aims to assess the differential impact of OOP expenditure and its components, such as expenditure on inpatient care, outpatient care and on drugs, across different income quintiles, between developed and less developed regions in India. It also attempts to measure poverty at disaggregated rural-urban and state levels. Based on Consumer Expenditure Survey (CES) data from the National Sample Survey (NSS), conducted in 1999–2000, the share of households’ expenditure on health services and drugs was calculated. The number of individuals below the state-specific rural and urban poverty line in 17 major states, with and without netting out OOP expenditure, was determined. This also enabled the calculation of the poverty gap or poverty deepening in each region. Estimates show that OOP expenditure is about 5% of total household expenditure (ranging from about 2% in Assam to almost 7% in Kerala) with a higher proportion being recorded in rural areas and affluent states. Purchase of drugs constitutes 70% of the total OOP expenditure. Approximately 32.5 million persons fell below the poverty line in 1999–2000 through OOP payments, implying that the overall poverty increase after accounting for OOP expenditure is 3.2% (as against a rise of 2.2% shown in earlier literature). Also, the poverty headcount increase and poverty deepening is much higher in poorer states and rural areas compared with affluent states and urban areas, except in the case of Maharashtra. High OOP payment share in total health expenditures did not always imply a high poverty headcount; state-specific economic and social factors played a role. The paper argues for better methods of capturing drugs expenditure in household surveys and recommends that special attention be paid to expenditures on drugs, in particular for the poor. Targeted policies in just five poor states to reduce OOP expenditure could help to prevent almost 60% of the poverty headcount increase through OOP payments.

Scrub infection is caused by Orientia tsutsugamushi, due to the bite of a chigger. It has a wide presentation, including febrile illness, ARDS (acute respiratory distress syndrome), and encephalopathy. However, we report a rare case of myosistis in Scrub Typhus.

INTRODUCTION:Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort.METHODS:Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis.RESULTS:A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence.DISCUSSION:Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.