Pandemic (H1N1) 2009 Cluster Analysis: A Preliminary Assessment

Pandemic (H1N1) 2009 virus has been causing major concerns around the world because of its epidemic potential, rapid dissemination, rate of mutations, and the number of fatalities. One way to gain an advantage over this virus is to use existing rapid bioinformatics tools to examine easily and inexpensively generated genetic sequencing data. We have used the protein sequences deposited with the National Center for Biotechnology Information (NCBI) for data mining to study the relationship among the Pandemic (H1N1) 2009 proteins. There are 11 proteins in the Pandemic (H1N1) 2009 virus, and analysis of sequences from 65 different locations around the globe has resulted in two major clusters. These clusters illustrate the Pandemic H1N1 2009 virus is already experiencing significant genetic drift and that rapid worldwide travel is affecting the distribution of genetically distinct isolates

Building A Culture of Scholarship with New Clinical Teachers By Writing About Social Justice Lawyering

This Article is a collection of essays about teaching social justice lawyering, as seen through the eyes of eight practitioners-in-residence in the clinical program at American University’s Washington College of Law (“WCL”). They include: Michelle Assad, Maria Dooner, Mariam Hinds, Jessica Millward, Citlalli Ochoa, Charles Ross, Anne Schaufele, and Caroline Wick. They teach in seven clinics, including the Civil Advocacy Clinic, the Criminal Justice Clinic, the Community Economic and Equity Development Clinic, the Disability Rights Law Clinic, the Immigrant Justice Clinic, the International Human Rights Law Clinic, and the Janet R. Spragens Federal Income Tax Clinic. We use the terms practitioner-in residence and practitioner interchangeably throughout this Article. These practitioners have full-time faculty status and represent a range of experience in our clinical program—from those who are in their first year of teaching in the program to those who have been teaching for several years and are near the end of their fellowships. Professors Assad, Millward, Schaufele, and Wick have now moved on to permanent teaching positions at other law schools, and Professor Dooner has returned to practice. They are all experienced lawyers who have brought their lawyering experiences in a variety of practice areas—criminal defense, criminal legal system reform, civil legal services, community and economic development, immigration, international human rights, employment, public benefits, health, tax law and policy, and special education—to their clinical teaching. They are diverse across a range of identities including race and ethnicity

High-Energy Cosmic Rays from Gamma-Ray Bursts

A model is proposed for the origin of cosmic rays (CRs) from ~10^14 eV to the highest energies, >10^20 eV. Gamma-Ray Bursts (GRBs) are assumed to inject CR protons and ions into the interstellar medium of star-forming galaxies--including the Milky Way--with a power law spectrum extending to a maximum energy ~10^20 eV. The CR spectrum near the knee is fit with CRs trapped in the Galactic halo that were accelerated and injected by an earlier Galactic GRB. These CRs diffuse in the disk and halo of the Galaxy due to gyroresonant pitch-angle scattering with MHD turbulence in the Galaxy's magnetic field. The preliminary (2001) KASCADE data through the knee of the CR spectrum are fit by a model with energy-dependent propagation of CR ions from a single Galactic GRB. Ultra-high energy CRs (UHECRs), with energies above the ankle are assumed to propagate rectilinearly with their spectrum modified by photo-pion, photo-pair, and expansion losses. We fit the measured UHECR spectrum assuming comoving luminosity densities of GRB sources consitent with possible star formation rate histories of the universe. For power-law CR proton injection p>2 this model implies that the nonthermal content in the GRB blast waves is hadronically dominated by a factor ~60-200. Calculations show that 100 TeV-100 PeV neutrinos could be detected several times per year from all GRBs in kilometer-scale neutrino detectors such as IceCube, for GRB blast-wave Doppler factors <~200. GLAST measurements of gamma-ray components and cutoffs will constrain the product of nonthermal baryon loading and radiative efficiency, limit the Doppler factor, and test this senario.Comment: 43 pages, 21 figures, to appear in Astropart. Phy

Do surgical care bundles reduce the risk of surgical site infections in patients undergoing colorectal surgery? A systematic review and cohort meta-analysis of 8,515 patients

Background. Care bundles are a strategy that can be used to reduce the risk of surgical site infection (SSI), but individual studies of care bundles report conflicting outcomes. This study assesses the effectiveness of care bundles to reduce SSI among patients undergoing colorectal surgery. Methods. We performed a systematic review and meta-analysis of randomized controlled trials, quasiexperimental studies, and cohort studies of care bundles to reduce SSI. The search strategy included database and clinical trials register searches from 2012 until June 2014, searching reference lists of retrieved studies and contacting study authors to obtain missing data. The Downs and Black checklist was used to assess the quality of all studies. Raw data were used to calculate pooled relative risk (RR) estimates using Cochrane Review Manager. The I2 statistic and funnel plots were performed to identify publication bias. Sensitivity analysis was carried out to examine the influence of individual data sets on pooled RRs. Results. Sixteen studies were included in the analysis, with 13 providing sufficient data for a metaanalysis. Most study bundles included core interventions such as antibiotic administration, appropriate hair removal, glycemic control, and normothermia. The SSI rate in the bundle group was 7.0% (328/ 4,649) compared with 15.1% (585/3,866) in a standard care group. The pooled effect of 13 studies with a total sample of 8,515 patients shows that surgical care bundles have a clinically important impact on reducing the risk of SSI compared to standard care with a CI of 0.55 (0.39–0.77; P = .0005). Conclusion. The systematic review and meta-analysis documents that use of an evidence-based, surgical care bundle in patients undergoing colorectal surgery significantly reduced the risk of SSI

Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays

We study transition form factors for radiative and rare semi-leptonic B-meson decays into light pseudoscalar or vector mesons, combining theoretical constraints and phenomenological information from Lattice QCD, light-cone sum rules, and dispersive bounds. We pay particular attention to form factor parameterisations which are based on the so-called series expansion, and study the related systematic uncertainties on a quantitative level. In this context, we also provide the NLO corrections to the correlation function between two flavour-changing tensor currents, which enters the unitarity constraints for the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion about relevance of unitarity bounds modified; form factor fits unaffected; references added; v3: discussion on truncation of series expansion added, matches version to be published in JHEP; v4: corrected typos in Tables 5 and

A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies

PURPOSE: This multicenter, open-label, dose-escalating, phase I study evaluated the safety, tolerability, pharmacokinetics and preliminary tumor response of a nanoparticulate formulation of paclitaxel (Nanotax®) administered intraperitoneally for multiple treatment cycles in patients with solid tumors predominantly confined to the peritoneal cavity for whom no other curative systemic therapy treatment options were available. METHODS: Twenty-one patients with peritoneal malignancies received Nanotax® in a modified dose-escalation approach utilizing an accelerated titration method. All patients enrolled had previously received chemotherapeutics and undergone surgical procedures, including 33 % with optimal debulking. Six doses (50–275 mg/m2) of Cremophor-free Nanotax® were administered intraperitoneally for one to six cycles (every 28 days). RESULTS: Intraperitoneal (IP) administration of Nanotax® did not lead to increases in toxicity over that typically associated with intravenous (IV) paclitaxel. No patient reported ≥Grade 2 neutropenia and/or ≥Grade 3 neurologic toxicities. Grade 3 thrombocytopenia unlikely related to study medication occurred in one patient. The peritoneal concentration–time profile of paclitaxel rose during the 2 days after dosing to peritoneal fluid concentrations 450–2900 times greater than peak plasma drug concentrations and remained elevated through the entire dose cycle. Best response assessments were made in 16/21 patients: Four patients were assessed as stable or had no response and twelve patients had increasing disease. Five of 21 patients with advanced cancers survived longer than 400 days after initiation of Nanotax® IP treatment. CONCLUSIONS: Compared to IV paclitaxel administration, Cremophor-free IP administration of Nanotax® provides higher and prolonged peritoneal paclitaxel levels with minimal systemic exposure and reduced toxicity

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study)

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis

Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort

<p>Abstract</p> <p>Background</p> <p>Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system.</p> <p>Methods</p> <p>Exposure to background particulate matter less than 10 μm in diameter (PM₁₀) and nitrogen dioxide (NO₂) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non-smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets.</p> <p>Results</p> <p>Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 μg/m³increase in PM₁₀levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO₂exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO₂exposure and an increased percentage of CD8+ T-cells.</p> <p>Conclusions</p> <p>These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies.</p