Transboundary Pollution and Cercla Liability: International Manufacturers\u27 Ability to Exploit Aerial Depositions

The Trail Smelter has a long and extensive history of pollution issues. The most recent claim against the Trail Smelter is the aerial deposition of hazardous waste theory. The Ninth Circuit has rejected attaching Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) liability to the Trail Smelter under the aerial deposition theory, but this holding cannot be accepted if the goal is to control pollution. Many issues arise with controlling transboundary pollution, including the enforcement of international agreements on the matter. In the absence of establishing an enforceable international treaty between the United States and Canada, CERCLA presents a viable option to help control transboundary air pollution. “Disposal’s” definition under CERCLA includes the term “deposit,” which promotes attaching CERCLA liability to foreign manufacturers for pollution harms that occur within the United States’ territorial boundaries. In order to reduce the harm caused by transboundary air pollution, and to promote CERCLA’s purpose, there is a need to recognize that CERCLA liability can attach to the aerial depositions of hazardous waste

The use of objective assessments in the evaluation of technical skills in cardiothoracic surgery: A systematic review

OBJECTIVES: With reductions in training time and intraoperative exposure, there is a need for objective assessments to measure trainee progression. This systematic review focuses on the evaluation of trainee technical skill performance using objective assessments in cardiothoracic surgery and its incorporation into training curricula. METHODS: Databases (EBSCOHOST, Scopus and Web of Science) and reference lists of relevant articles for studies that incorporated objective assessment of technical skills of trainees/residents in cardiothoracic surgery were included. Data extraction included task performed; assessment setting and tool used; number/level of assessors; study outcome and whether the assessments were incorporated into training curricula. The methodological rigour of the studies was scored using the Medical Education Research Study Quality Instrument (MERSQI). RESULTS: Fifty-four studies were included for quantitative synthesis. Six were randomized-controlled trials. Cardiac surgery was the most common speciality utilizing objective assessment methods with coronary anastomosis the most frequently tested task. Likert-based assessment tools were most commonly used (61%). Eighty-five per cent of studies were simulation-based with the rest being intraoperative. Expert surgeons were primarily used for objective assessments (78%) with 46% using blinding. Thirty (56%) studies explored objective changes in technical performance with 97% demonstrating improvement. The other studies were primarily validating assessment tools. Thirty-nine per cent of studies had established these assessment tools into training curricula. The mean ± standard deviation MERSQI score for all studies was 13.6 ± 1.5 demonstrating high validity. CONCLUSIONS: Despite validated technical skill assessment tools being available and demonstrating trainee improvement, their regular adoption into training curricula is lacking. There is a need to incorporate these assessments to increase the efficiency and transparency of training programmes for cardiothoracic surgeons

Tricuspid valve intervention at the time of pulmonary valve replacement in adults with congenital heart disease: A systematic review and meta-analysis

Background Tricuspid regurgitation (TR) is a common finding in adults with congenital heart disease referred for pulmonary valve replacement (PVR). However, indications for combined valve surgery remain controversial. This study aimed to evaluate early results of concomitant tricuspid valve intervention (TVI) at the time of PVR. Methods and Results Observational studies comparing TVI+PVR and isolated PVR were identified by a systematic search of published research. Random-effects meta-analysis was performed, comparing outcomes between the 2 groups. Six studies involving 749 patients (TVI+PVR, 278 patients; PVR, 471 patients) met the eligibility criteria. In the pooled analysis, both TVI+PVR and PVR reduced TR grade, pulmonary regurgitation grade, right ventricular end-diastolic volume, and right ventricular end-systolic volumes. TVI+PVR, but not PVR, was associated with a decrease in tricuspid valve annulus size (mean difference, -6.43 mm, 95% CI, -10.59 to -2.27

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Lignosulfonic Acid Exhibits Broadly Anti-HIV-1 Activity – Potential as a Microbicide Candidate for the Prevention of HIV-1 Sexual Transmission

Some secondary metabolites from plants show to have potent inhibitory activities against microbial pathogens, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), Treponema pallidum, Neisseria gonorrhoeae, etc. Here we report that lignosulfonic acid (LSA), a polymeric lignin derivative, exhibits potent and broad activity against HIV-1 isolates of diverse subtypes including two North America strains and a number of Chinese clinical isolates values ranging from 21.4 to 633 nM. Distinct from other polyanions, LSA functions as an entry inhibitor with multiple targets on viral gp120 as well as on host receptor CD4 and co-receptors CCR5/CXCR4. LSA blocks viral entry as determined by time-of-drug addiction and cell-cell fusion assays. Moreover, LSA inhibits CD4-gp120 interaction by blocking the binding of antibodies specific for CD4-binding sites (CD4bs) and for the V3 loop of gp120. Similarly, LSA interacts with CCR5 and CXCR4 via its inhibition of specific anti-CCR5 and anti-CXCR4 antibodies, respectively. Interestingly, the combination of LSA with AZT and Nevirapine exhibits synergism in viral inhibition. For the purpose of microbicide development, LSA displays low in vitro cytotoxicity to human genital tract epithelial cells, does not stimulate NF-κB activation and has no significant up-regulation of IL-1α/β and IL-8 as compared with N-9. Lastly, LSA shows no adverse effect on the epithelial integrity and the junctional protein expression. Taken together, our findings suggest that LSA can be a potential candidate for tropical microbicide

Non-specific mechanisms in orthodox and CAM management of low back pain (MOCAM): theoretical framework and protocol for a prospective cohort study.

INTRODUCTION: Components other than the active ingredients of treatment can have substantial effects on pain and disability. Such 'non-specific' components include: the therapeutic relationship, the healthcare environment, incidental treatment characteristics, patients' beliefs and practitioners' beliefs. This study aims to: identify the most powerful non-specific treatment components for low back pain (LBP), compare their effects on patient outcomes across orthodox (physiotherapy) and complementary (osteopathy, acupuncture) therapies, test which theoretically derived mechanistic pathways explain the effects of non-specific components and identify similarities and differences between the therapies on patient-practitioner interactions. METHODS AND ANALYSIS: This research comprises a prospective questionnaire-based cohort study with a nested mixed-methods study. A minimum of 144 practitioners will be recruited from public and private sector settings (48 physiotherapists, 48 osteopaths and 48 acupuncturists). Practitioners are asked to recruit 10-30 patients each, by handing out invitation packs to adult patients presenting with a new episode of LBP. The planned multilevel analysis requires a final sample size of 690 patients to detect correlations between predictors, hypothesised mediators and the primary outcome (self-reported back-related disability on the Roland-Morris Disability Questionnaire). Practitioners and patients complete questionnaires measuring non-specific treatment components, mediators and outcomes at: baseline (time 1: after the first consultation for a new episode of LBP), during treatment (time 2: 2 weeks post-baseline) and short-term outcome (time 3: 3 months post-baseline). A randomly selected subsample of participants in the questionnaire study will be invited to take part in a nested mixed-methods study of patient-practitioner interactions. In the nested study, 63 consultations (21/therapy) will be audio-recorded and analysed quantitatively and qualitatively, to identify communication practices associated with patient outcomes. ETHICS AND DISSEMINATION: The protocol is approved by the host institution's ethics committee and the NHS Health Research Authority Research Ethics Committee. Results will be disseminated via peer-reviewed journal articles, conferences and a stakeholder workshop

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Factors Associated with Surgical re-Replacement or Transcatheter Pulmonary Valve Insertion of the Second Pulmonary Conduit

Patients receiving a right ventricle-to-pulmonary artery conduit (PC) in infancy will require successive procedures or replacements, each with variable longevity. We sought to identify factors associated with time-related risk of a subsequent surgical replacement (PC3) or transcatheter pulmonary valve insertion (TPVI) after a second surgically-placed PC (PC2). From 2002 to 2016, 630 patients were enrolled after initial valved PC insertion at ageM.Sc