The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension

Pulmonary hypertension (PH) is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH). Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5) inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH

Analysis of parameters that affect human hematopoietic cell outputs in mutant c-kit-immunodeficient mice.

Xenograft models are transforming our understanding of the output capabilities of primitive human hematopoietic cells in vivo. However, many variables that affect posttransplantation reconstitution dynamics remain poorly understood. Here, we show that an equivalent level of human chimerism can be regenerated from human CD34(+) cord blood cells transplanted intravenously either with or without additional radiation-inactivated cells into 2- to 6-month-old NOD-Rag1(-/-)-IL2Rγc(-/-) (NRG) mice given a more radioprotective conditioning regimen than is possible in conventionally used, repair-deficient NOD-Prkdc(scid/scid)-IL2Rγc(-/-) (NSG) hosts. Comparison of sublethally irradiated and non-irradiated NRG mice and W(41)/W(41) derivatives showed superior chimerism in the W(41)-deficient recipients, with some differential effects on different lineage outputs. Consistently superior outputs were observed in female recipients regardless of their genotype, age, or pretransplantation conditioning, with greater differences apparent later after transplantation. These results define key parameters for optimizing the sensitivity and minimizing the intraexperimental variability of human hematopoietic xenografts generated in increasingly supportive immunodeficient host mice. Exp Hematol 2017 Apr; 48:41-49

Xanthus: Push-button Orchestration of Host Provenance Data Collection

Host-based anomaly detectors generate alarms by inspecting audit logs for suspicious behavior. Unfortunately, evaluating these anomaly detectors is hard. There are few high-quality, publicly-available audit logs, and there are no pre-existing frameworks that enable push-button creation of realistic system traces. To make trace generation easier, we created Xanthus, an automated tool that orchestrates virtual machines to generate realistic audit logs. Using Xanthus' simple management interface, administrators select a base VM image, configure a particular tracing framework to use within that VM, and define post-launch scripts that collect and save trace data. Once data collection is finished, Xanthus creates a self-describing archive, which contains the VM, its configuration parameters, and the collected trace data. We demonstrate that Xanthus hides many of the tedious (yet subtle) orchestration tasks that humans often get wrong; Xanthus avoids mistakes that lead to non-replicable experiments.Comment: 6 pages, 1 figure, 7 listings, 1 table, worksho

Identifying Patients at High Risk of a Cardiovascular Event in the Near Future Current Status and Future Directions: Report of a National Heart, Lung, and Blood Institute Working Group

The National Heart, Lung, and Blood Institute convened a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the “near term.” The working group members defined near-term as occurring within 1 year of the time of assessment. The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility. This report presents highlights of these reviews and a summary of suggested research directions

Maximal care considerations when treating patients with end-stage heart failure: ethical and procedural quandaries in management of the very sick

Deciding who should receive maximal technological treatment options and who should not represents an ethical, moral, psychological and medico-legal challenge for health care providers. Especially in patients with chronic heart failure, the ethical and medico-legal issues associated with providing maximal possible care or withholding the same are coming to the forefront. Procedures, such as cardiac transplantation, have strict criteria for adequate candidacy. These criteria for subsequent listing are based on clinical outcome data but also reflect the reality of organ shortage. Lack of compliance and non-adherence to lifestyle changes represent relative contraindications to heart transplant candidacy. Mechanical circulatory support therapy using ventricular assist devices is becoming a more prominent therapeutic option for patients with end-stage heart failure who are not candidates for transplantation, which also requires strict criteria to enable beneficial outcome for the patient. Physicians need to critically reflect that in many cases, the patient’s best interest might not always mean pursuing maximal technological options available. This article reflects on the multitude of critical issues that health care providers have to face while caring for patients with end-stage heart failure

A survey and classification of storage deduplication systems

The automatic elimination of duplicate data in a storage system commonly known as deduplication is increasingly accepted as an effective technique to reduce storage costs. Thus, it has been applied to different storage types, including archives and backups, primary storage, within solid state disks, and even to random access memory. Although the general approach to deduplication is shared by all storage types, each poses specific challenges and leads to different trade-offs and solutions. This diversity is often misunderstood, thus underestimating the relevance of new research and development. The first contribution of this paper is a classification of deduplication systems according to six criteria that correspond to key design decisions: granularity, locality, timing, indexing, technique, and scope. This classification identifies and describes the different approaches used for each of them. As a second contribution, we describe which combinations of these design decisions have been proposed and found more useful for challenges in each storage type. Finally, outstanding research challenges and unexplored design points are identified and discussed.This work is funded by the European Regional Development Fund (EDRF) through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the Fundacao para a Ciencia e a Tecnologia (FCT; Portuguese Foundation for Science and Technology) within project RED FCOMP-01-0124-FEDER-010156 and the FCT by PhD scholarship SFRH-BD-71372-2010

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Sensory Communication

Contains table of contents on Section 2, an introduction, reports on eleven research projects and a list of publications.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Grant 5 R01 DC00270National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00100National Institutes of Health Contract 7 R29 DC00428National Institutes of Health Grant 2 R01 DC00126U.S. Air Force - Office of Scientific Research Grant AFOSR 90-0200U.S. Navy - Office of Naval Research Grant N00014-90-J-1935National Institutes of Health Grant 5 R29 DC00625U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-181

The global spread of misinformation on spiders

Non peer reviewe