HLA-Associated viral mutations are common in human immunodeficiency virus type 1 elite controllers

Elite controllers (EC) of human immunodeficiency virus type 1 (HTV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8+ T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC., compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HTV-1 infection

Use of the Spine AdVerse Events Severity (SAVES) System to Categorize and Report Adverse Events in Spine Surgery.

Introduction: Analysis of adverse events (AEs) in spine surgery has historically been retrospective, utilizing hospital administrative data. Our objective was to determine the incidence, severity and effect on hospital length of stay (LOS) for AEs in spine surgery using the Spine AdVerse Events Severity (SAVES V2) system. Methods: AEs for all surgical spine patients at our institution were prospectively collected for 18 months and correlated with retrospective data from operative reports and H&Ps. Statistical analyses compared patient demographics, diagnoses, and surgical characteristics to hospital length of stay and likelihood of adverse events. Results: This system captured 75% (765/977) of surgical cases for all indications over the study period. 73% (541/743) of patients experienced at least one AE, with an average of 1.2 AEs per patient (range 0-5). The most common AEs were pain control (31%), urinary retention (9.7%), wound infection (6.3%), and incidental durotomy (5.8%). For patients experiencing at least one AE, 30% had no effect on LOS, 48% increased LOS by 1-2 days, 15% increased LOS by 3-7 days, and 7% had prolonged LOS greater than 8 days. Our system captured 25.4% more adverse events (60.0% vs. 34.6%) than hospital administrative data. Univariate analysis revealed patient age, emergent surgery, diagnostic and surgical categories, and spine region to be predictors of both AEs and LOS. Instrumentation was predictive of increased LOS but not AEs. The type of AE was strongly associated with LOS. Multivariable analysis of AE likelihood demonstrated emergent surgery to be the strongest independent predictor with an adjusted odds ratio of 8.5 versus elective surgery. Discussion: Spine surgery is associated with a high incidence of adverse events, which often prolong hospital length of stay. Better characterization of adverse events and their predictors could lead to improved management strategies that reduce patient morbidity and mortality

Management of blunt extracranial traumatic cerebrovascular injury: a multidisciplinary survey of current practice

<p>Abstract</p> <p>Background</p> <p>Extracranial traumatic cerebrovascular injury (TCVI) is present in 1-3% of all blunt force trauma patients. Although options for the management of patients with these lesions include anticoagulation, antiplatelet agents, and endovascular treatment, the optimal management strategy for patients with these lesions is not yet established.</p> <p>Objective</p> <p>Multidisciplinary survey of clinicians about current management of TCVI.</p> <p>Methods</p> <p>A six-item multiple-choice survey was sent by electronic mail to a total of 11,784 neurosurgeons, trauma surgeons, stroke neurologists, and interventional radiologists. The survey included questions about their choice of imaging, medical management, and the use of endovascular techniques. Survey responses were analyzed according to stated specialty.</p> <p>Results</p> <p>Seven hundred eighty-five (6.7%) responses were received. Overall, a total of 325 (42.8%) respondents favored anticoagulation (heparin and/or warfarin), 247 (32.5%) favored antiplatelet drugs, 130 (17.1%) preferred both anticoagulation and antiplatelet drugs, and 57 (7.5%) preferred stenting and/or embolization. Anticoagulation was the most commonly preferred treatment among vascular surgeons (56.9%), neurologists (50.2%) and neurosurgeons (40.7%), whereas antiplatelet agents were the most common preferred treatment among trauma surgeons (41.5%). Overall, 158 (20.7%) of respondents recommended treatment of asymptomatic dissections and traumatic aneurysms, 211 (27.7%) did not recommend it, and 39.4% recommended endovascular treatment only if there is worsening of the lesion on follow-up imaging.</p> <p>Conclusions</p> <p>These data demonstrate the wide variability of physicians' management of traumatic cerebrovascular injury, both on an individual basis, and between specialties. These findings underscore the need for multicenter, randomized trials in this field.</p

Thirty Years After Michael E. Porter: What Do We Know About Business Exit?

Although a business exit is an important corporate change initiative, the buyer’s side seems to be more appealing to management researchers than the seller’s because acquisitions imply growth, i.e., success. Yet from an optimistic viewpoint, business exit can effectively create value for the selling company. In this paper we attempt to bring the relevance of the seller’s side back into our consciousness by asking: What do we know about business exit? We start our exploration with Porter (1976), focusing on literature that investigates the antecedents of, barriers to, and outcomes of business exit. We also include studies from related fields such as finance and economics.1 Through this research we determine three clusters of findings: factors promoting business exit, exit barriers, and exit outcomes. Overall, it is the intention of this paper to highlight the importance of business exit for research and practice. Knowing what we know about business exits and their high financial value we should bear in mind that exit need not mean failure but a new beginning for a corporation

Pharmacokinetics and Antiretroviral Activity of Lamivudine Alone or When Coadministered with Zidovudine in Human Immunodeficiency Virus Type 1-Infected Pregnant Women and Their Offspring

The safety, pharmacokinetics, and antiretroviral activity of lamivudine alone and in combination with zidovudine was studied in pregnant women infected with human immunodeficiency virus type 1 (HIV-1) and their neonates. Women received the drugs orally from week 38 of pregnancy to 1 week after delivery. Neonate therapy began 12 h after delivery and continued for 1 week. Both treatment regimens were well-tolerated in women and newborns. Lamivudine and zidovudine pharmacokinetics in pregnant women were similar to those in nonpregnant adults. Lamivudine and zidovudine freely crossed the placenta and were secreted in breast milk. Neonatal lamivudine clearance was about half that in pediatric patients; zidovudine clearance was consistent with previous reports. HIV-1 RNA could be quantified in 17 of the 20 women. At the onset of labor/delivery, mean virus load had decreased by ∼1.5 log10 copies/mL in both treatment cohorts. Although not definitive for HIV-1 infection status, all neonates had HIV-1 RNA levels below the limit of quantification at birth and at ages 1 and 2 week

Natural Products Chemistry and Taxonomy of the Marine Cyanobacterium Blennothrix cantharidosmum

A Papua New Guinea field collection of the marine cyanobacterium Blennothrix cantharidosmum was investigated for its cytotoxic constituents. Bioassay-guided isolation defined the cytotoxic components as the known compounds lyngbyastatins 1 and 3. However, six new acyl proline derivatives, tumonoic acids D−I, plus the known tumonoic acid A were also isolated. Their planar structures were defined from NMR and MS data, while their stereostructures followed from a series of chiral chromatographies, degradation sequences, and synthetic approaches. The new compounds were tested in an array of assays, but showed only modest antimalarial and inhibition of quorum sensing activities. Nevertheless, these are the first natural products to be reported from this genus, and this inspired a detailed morphologic and 16S rDNA-based phylogenetic analysis of the producing organism

Quasi-probability representations of quantum theory with applications to quantum information science

This article comprises a review of both the quasi-probability representations of infinite-dimensional quantum theory (including the Wigner function) and the more recently defined quasi-probability representations of finite-dimensional quantum theory. We focus on both the characteristics and applications of these representations with an emphasis toward quantum information theory. We discuss the recently proposed unification of the set of possible quasi-probability representations via frame theory and then discuss the practical relevance of negativity in such representations as a criteria for quantumness.Comment: v3: typos fixed, references adde

Impacts of economic inequality on healthcare worker safety at the onset of the COVID-19 pandemic : cross-sectional analysis of a global survey

Objectives To assess the extent to which protection of healthcare workers (HCWs) as COVID-19 emerged was associated with economic inequality among and within countries. Design Cross-sectional analysis of associations of perceptions of workplace risk acceptability and mitigation measure adequacy with indicators of respondents’ respective country’s economic income level (World Bank assessment) and degree of within-country inequality (Gini index). Setting A global self-administered online survey. Participants 4977 HCWs and healthcare delivery stakeholders from 161 countries responded to health and safety risk questions and a subset of 4076 (81.2%) answered mitigation measure questions. The majority (65%) of study participants were female. Results While the levels of risk being experienced at the pandemic’s onset were consistently deemed as unacceptable across all groupings, participants from countries with less income inequality were somewhat less likely to report unacceptable levels of risk to HCWs regarding both workplace environment (OR=0.92, p=0.012) and workplace organisational factors (OR=0.93, p=0.017) compared with counterparts in more unequal national settings. In contrast, considerable variation existed in the degree to which mitigation measures were considered adequate. Adjusting for other influences through a logistic regression analysis, respondents from lower middle-income and low-income countries were comparatively much more likely to assess both occupational health and safety (OR=10.91, p≤0.001) and infection prevention and control (IPC) (OR=6.61, p=0.001) protection measures as inadequate, despite much higher COVID-19 rates in wealthier countries at the time of the survey. Greater within-country income inequality was also associated with perceptions of less adequate IPC measures (OR=0.94, p=0.025). These associations remained significant when accounting for country-level differences in occupational and gender composition of respondents, including specifically when only female care providers, our study’s largest and most at-risk subpopulation, were examined. Conclusions Economic inequality threatens resilience of health systems that rely on health workers working safely to provide needed care during emerging pandemics