Use of a handheld Doppler to measure brachial and femoral artery occlusion pressure

Objective: Measurement of arterial occlusion pressure (AOP) is essential to the safe and effective use of blood flow restriction during exercise. Use of a Doppler ultrasound (US) is the “gold standard” method to measure AOP. Validation of a handheld Doppler (HHDOP) device to measure AOP could make the measurement of AOP more accessible to practitioners in the field. The purpose of this study was to determine the accuracy of AOP measurements of the brachial and femoral arteries using an HHDOP.Methods: We simultaneously measured AOP using a “gold standard” US and a HHDOP in the dominant and non-dominant arms (15 males; 15 females) and legs (15 males; 15 females).Results: There were no differences in limb circumference or limb volume in the dominant and non-dominant arms and legs between males and females or between the dominant and non-dominant arms and legs of males and females. The differences between US and HHDOP measures of AOP in the dominant and non-dominant arms and legs were either not significant or small (<10 mmHg) and of little practical importance. There were no sex differences in AOP measurements of the femoral artery (p > 0.60). Bland–Altman analysis yielded an average bias (−0.65 mmHg; −2.93 mmHg) and reasonable limits of agreement (±5.56 mmHg; ±5.58 mmHg) between US and HHDOP measures of brachial and femoral artery AOP, respectively.Conclusion: HHDOP yielded acceptable measures of AOP of the brachial and femoral arteries and can be used to measure AOP by practitioners for the safe and effective use of blood flow restriction. Due to the potential differences in AOP between dominant and non-dominant limbs, AOP should be measured in each limb

Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study

Purpose: The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas. Patients and Methods: Patients were treated with weekly intratumoral injections of MIW815 (50–3,200 μg) on a 3-weeks-on/1-week-off schedule or once every 4 weeks, plus a fixed dose of spartalizumab (400 mg) intravenously every 4 weeks. Results: Common adverse events were pyrexia (n = 23; 22%), injection site pain (n = 21; 20%), and diarrhea (n = 12; 11%). Overall response rate was 10.4%. The MTD was not reached. Pharmacodynamic biomarker analysis demonstrated on-target activity. Conclusions: The combination of MIW815 and spartalizumab was well tolerated in patients with advanced/metastatic cancers, including in patients with anti-PD-1 refractory disease. Minimal antitumor responses were seen

B Physics at the Tevatron: Run II and Beyond

This report provides a comprehensive overview of the prospects for B physics at the Tevatron. The work was carried out during a series of workshops starting in September 1999. There were four working groups: 1) CP Violation, 2) Rare and Semileptonic Decays, 3) Mixing and Lifetimes, 4) Production, Fragmentation and Spectroscopy. The report also includes introductory chapters on theoretical and experimental tools emphasizing aspects of B physics specific to hadron colliders, as well as overviews of the CDF, D0, and BTeV detectors, and a Summary.Comment: 583 pages. Further information on the workshops, including transparencies, can be found at the workshop's homepage: http://www-theory.lbl.gov/Brun2/. The report is also available in 2-up http://www-theory.lbl.gov/Brun2/report/report2.ps.gz or chapter-by-chapter http://www-theory.lbl.gov/Brun2/report

The Structure and Origin of Switchbacks: Parker Solar Probe Observations

Switchbacks are rapid magnetic field reversals that last from seconds to hours. Current Parker Solar Probe (PSP) observations pose many open questions in regards to the nature of switchbacks. For example, are they stable as they propagate through the inner heliosphere, and how are they formed? In this work, we aim to investigate the structure and origin of switchbacks. In order to study the stability of switchbacks, we suppose the small scale current sheets therein may work to braid and stabilize the switchbacks. Thus, we use the partial variance of increments method to identify the small scale current sheets, and then compare their distributions in switchbacks. With more than one thousand switchbacks identified with PSP observations in seven encounters, we find many more current sheets inside than outside switchbacks, indicating that these micro-structures should work to stabilize the S-shape structures of switchbacks. Additionally, with the helium measurements, we study the variations of helium abundance ratios and alpha-proton differential speeds to trace switchbacks to their origins. We find both helium-rich and helium-poor populations in switchbacks, implying the switchbacks could originate from both closed and open magnetic field regions in the Sun. Moreover, we observe that the alpha-proton differential speeds also show complex variations as compared to the local Alfv\'en speed. The joint distributions of both parameters show that low helium abundance together with low differential speed is the dominant state in switchbacks. The presence of small scale current sheets in switchbacks along with the helium features are in line with the hypothesis that switchbacks could originate from the Sun via interchange reconnection process. However, other formation mechanisms are not excluded

Serendipitous discovery of a dying Giant Radio Galaxy associated with NGC 1534, using the Murchison Widefield Array

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.Recent observations with the Murchison Widefield Array at 185~MHz have serendipitously unveiled a heretofore unknown giant and relatively nearby ($z = 0.0178$) radio galaxy associated with NGC\,1534. The diffuse emission presented here is the first indication that NGC\,1534 is one of a rare class of objects (along with NGC\,5128 and NGC\,612) in which a galaxy with a prominent dust lane hosts radio emission on scales of $\sim$700\,kpc. We present details of the radio emission along with a detailed comparison with other radio galaxies with disks. NGC1534 is the lowest surface brightness radio galaxy known with an estimated scaled 1.4-GHz surface brightness of just 0.2\,mJy\,arcmin$^{-2}$. The radio lobes have one of the steepest spectral indices yet observed: $\alpha=-2.1\pm0.1$, and the core to lobe luminosity ratio is $Peer reviewe

Rethinking how development assistance for health can catalyse progress on primary health care

Global campaigns to control HIV, tuberculosis, malaria, and vaccine-preventable illnesses showed that large-scale impact can be achieved by using additional international financing to support selected, evidence-based, high-impact investment areas and to catalyse domestic resource mobilisation. Building on this paradigm, we make the case for targeting additional international funding for selected high-impact investments in primary health care. We have identified and costed a set of concrete, evidence-based investments that donors could support, which would be expected to have major impacts at an affordable cost. These investments are in: (1) individuals and communities empowered to engage in health decision making, (2) a new model of people-centred primary care, and (3) next generation community health workers. These three areas would be supported by strengthening two cross-cutting elements of national systems. The first is the digital tools and data that support facility, district, and national managers to improve processes, quality of care, and accountability across primary health care. The second is the educational, training, and supervisory systems needed to improve the quality of care. We estimate that with an additional international investment of between US$1·87 billion in a low-investment scenario and$3·85 billion in a high-investment scenario annually over the next 3 years, the international community could support the scale-up of this evidence-based package of investments in the 59 low-income and middle-income countries that are eligible for external financing from the World Bank Group's International Development Association

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

Background and aimsAutoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens.MethodsWe retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary endpoint was complete remission, defined as the absence of clinical symptoms and resolution of the index radiological pancreatic abnormalities attributed to AIP.ResultsWe included 735 individuals with AIP (69% male; median age 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, while 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower ( 2 weeks (OR 0.908; 95%CI 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (OR 0.639; 95%CI 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid tapering duration, induction treatment duration, and total cumulative dose.ConclusionPatients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens

Inverting the model of genomics data sharing with the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space

The NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL; https://anvilproject.org) was developed to address a widespread community need for a unified computing environment for genomics data storage, management, and analysis. In this perspective, we present AnVIL, describe its ecosystem and interoperability with other platforms, and highlight how this platform and associated initiatives contribute to improved genomic data sharing efforts. The AnVIL is a federated cloud platform designed to manage and store genomics and related data, enable population-scale analysis, and facilitate collaboration through the sharing of data, code, and analysis results. By inverting the traditional model of data sharing, the AnVIL eliminates the need for data movement while also adding security measures for active threat detection and monitoring and provides scalable, shared computing resources for any researcher. We describe the core data management and analysis components of the AnVIL, which currently consists of Terra, Gen3, Galaxy, RStudio/Bioconductor, Dockstore, and Jupyter, and describe several flagship genomics datasets available within the AnVIL. We continue to extend and innovate the AnVIL ecosystem by implementing new capabilities, including mechanisms for interoperability and responsible data sharing, while streamlining access management. The AnVIL opens many new opportunities for analysis, collaboration, and data sharing that are needed to drive research and to make discoveries through the joint analysis of hundreds of thousands to millions of genomes along with associated clinical and molecular data types