Efficient verification of hazard-freedom in gate-level timed asynchronous circuits

Journal ArticleAbstract-This paper presents an efficient method for verifying hazard-freedom in gate-level timed asynchronous circuits. Timed circuits are a class of asynchronous circuits that are optimized using explicit timing information. In asynchronous circuits, correct operation requires that there are no hazards in the circuit implementation. Therefore, when designing an asynchronous circuit, each internal node and output of the circuit must be verified for hazard-freedom to ensure correct operation. Current verification algorithms for timed circuits require an explicit state exploration that often results in state explosion for even modest-sized examples. The goal of this paper is to abstract the behavior of internal nodes and utilize this information to make a conservative determination of hazard-freedom for each node in the circuit. Experimental results indicate that this approach is substantially more efficient than existing timing verification tools. These results also indicate that this method scales well for large examples that could not be previously analyzed, in that it is capable of analyzing these circuits in less than a second. While this method is conservative in that some false hazards may be reported, our results indicate that their number is small

Associations of Physiological Factors, Age, and Sensory Over-Responsivity with Food Selectivity in Children with Autism Spectrum Disorders

PURPOSE: The aim of this study was to investigate the relationship among physiological factors, age, sensory over-responsivity (SOR) and food selectivity in children with autism spectrum disorders (ASD). METHODS: One hundred forty-one parents of children with ASD were recruited through a national autism organization, Autism Speaks, to fill out a survey regarding their child’s mealtime behavior. Survey contained items to measure the severity of food selectivity behavior, the presence of physiological factors (i.e., reflux, constipation, food allergies and the need for a specialized diet) and sensory over-responsivity (SOR). Results were analyzed using Chi Square, ANOVA and logistic regression. RESULTS: No relationship between physiological factors and level of food selectivity was found. Older children in the 3-9 year old range did not have more foods in their diet repertoire than younger children. Finally, children with fewer than 10 and those with 11-20 foods in their diet (i.e., severe food selectivity and moderate food selectivity respectively) were found to have significantly higher scores on a measure of SOR when compared to children with 21+ foods (typical selectivity). CONCLUSIONS: When addressing food selectivity in children with ASD, consideration of the possibility that the child may not outgrow restricted diets is warranted. Also, treatment for food selectivity may be more effective if SOR is included in protocol

Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence

Activation of the endothelin A receptor (ETA) by endothelin-1 (ET-1) mediates events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in tumours. Specific blockade of ETA may have anticancer effects, while retaining beneficial endothelin B receptor (ETB)-mediated effects such as apoptosis and clearance of ET-1. ZD4054 is an orally active, specific ETA antagonist in clinical development. In receptor-binding studies, ZD4054 specifically bound to ETA with high affinity; no binding was detected at ETB. In a randomised placebo-controlled trial in eight healthy volunteers, a single oral dose of ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion of ET-1, thus providing clinical evidence of ETA blockade. ETB blockade was assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers. For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h were within the placebo reference range (a rise in ET-1 would indicate ETB blockade) and there was no evidence of dose-related changes. These data confirm the specificity of ZD4054 for ETA, with no activity at ETB in a clinical or preclinical setting. As a result of this specificity, ZD4054 has the potential to block multiple ETA-induced pathological processes, while allowing beneficial ETB-mediated processes to continue, which may, in turn, lead to an effective cancer therapy

Integrating Palliative Care Into the PICU: A Report From the Improving Palliative Care in the ICU Advisory Board

Objective: This review highlights benefits that patients, families and clinicians can expect to realize when palliative care is intentionally incorporated into the PICU. Data Sources: We searched the MEDLINE database from inception to January 2014 for English-language articles using the terms palliative care or end of life care or supportive care and pediatric intensive care. We also hand-searched reference lists and author files and relevant tools on the Center to Advance Palliative Care website. Study Selection: Two authors (physicians with experience in pediatric intensive care and palliative care) made final selections. Data Extraction: We critically reviewed the existing data and tools to identify strategies for incorporating palliative care into the PICU. Data Synthesis: The Improving Palliative Care in the ICU Advisory Board used data and experience to address key questions relating to: pain and symptom management, enhancing quality of life, communication and decision-making, length of stay, sites of care, and grief and bereavement. Conclusions: Palliative care should begin at the time of a potentially life-limiting diagnosis and continue throughout the disease trajectory, regardless of the expected outcome. Although the PICU is often used for short term postoperative stabilization, PICU clinicians also care for many chronically ill children with complex underlying conditions and others receiving intensive care for prolonged periods. Integrating palliative care delivery into the PICU is rapidly becoming the standard for high quality care of critically ill children. Interdisciplinary ICU staff can take advantage of the growing resources for continuing education in pediatric palliative care principles and interventions

The Human Microbiome Project: A Community Resource for the Healthy Human Microbiome

The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. Microbial ecologists, realizing that >99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ [5], primarily by sequencing the 16S ribosomal RNA gene (16S) as a phylogenetic and taxonomic marker to identify members of microbial communities [6]. The need to develop corresponding new methods for culture-independent studies [7],[8] in turn precipitated a sea change in the study of microbes and human health, inspiring the new term “metagenomics" [9] both to describe a technological approach—sequencing and analysis of the genes from whole communities rather than from individual genomes—and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions [10] culminated in a National Academy of Science report [11], which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.National Institutes of Health (U.S.) (grant U54HG004969)National Institutes of Health (U.S.) (grant U54HG004973)National Institutes of Health (U.S.) (grant U54AI084844)National Institutes of Health (U.S.) (grant U01HG004866)National Institutes of Health (U.S.) (grant R01HG005969)National Institutes of Health (U.S.) (grant R01HG004872)United States. Army Research Office (grant W911NF-11-1-0473)National Science Foundation (U.S.) (NSF DBI-1053486)Howard Hughes Medical Institute (Early Career Scientist

Integrating Palliative Care Into the Care of Neurocritically Ill Patients: A Report From the Improving Palliative Care in the ICU Project Advisory Board and the Center to Advance Palliative Care

OBJECTIVES: To describe unique features of neurocritical illness that are relevant to provision of high-quality palliative care; to discuss key prognostic aids and their limitations for neurocritical illnesses; to review challenges and strategies for establishing realistic goals of care for patients in the neuro-ICU; and to describe elements of best practice concerning symptom management, limitation of life support, and organ donation for the neurocritically ill. DATA SOURCES: A search of PubMed and MEDLINE was conducted from inception through January 2015 for all English-language articles using the term palliative care, supportive care, end-of-life care, withdrawal of life-sustaining therapy, limitation of life support, prognosis, or goals of care together with neurocritical care, neurointensive care, neurological, stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or brain injury. DATA EXTRACTION AND SYNTHESIS: We reviewed the existing literature on delivery of palliative care in the neurointensive care unit setting, focusing on challenges and strategies for establishing realistic and appropriate goals of care, symptom management, organ donation, and other considerations related to use and limitation of life-sustaining therapies for neurocritically ill patients. Based on review of these articles and the experiences of our interdisciplinary/interprofessional expert advisory board, this report was prepared to guide critical care staff, palliative care specialists, and others who practice in this setting. CONCLUSIONS: Most neurocritically ill patients and their families face the sudden onset of devastating cognitive and functional changes that challenge clinicians to provide patient-centered palliative care within a complex and often uncertain prognostic environment. Application of palliative care principles concerning symptom relief, goal setting, and family emotional support will provide clinicians a framework to address decision making at a time of crisis that enhances patient/family autonomy and clinician professionalism

Basal Gene Expression by Lung CD4+ T Cells in Chronic Obstructive Pulmonary Disease Identifies Independent Molecular Correlates of Airflow Obstruction and Emphysema Extent

Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial. To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant. Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis. In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production. Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines. This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length. As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts. Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent). Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also exists in some smokers with normal spirometry, and may contribute to development and progression of specific COPD phenotypes. Trial Registration ClinicalTrials.gov as NCT0028122

Francisella tularensis Transmission by Solid Organ Transplantation, 20171.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation

Patterns and predictors of adherence to statin therapy among older patients: Protocol for a systematic review

Background: The benefits of statin therapy are significantly compromised by noncompliance. Although elderly patients may have particular challenges with medication adherence and persistence, previous reviews on statin adherence have not focused on this population. Additionally, comparisons of adherence and persistence specific to statin indication (primary or secondary prevention) have not been thoroughly explored.Objective: We aim to assess the extent of, and factors associated with, adherence and persistence to statin therapy among older populations (aged ≥65 years).Methods: A systematic review will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Searches will be performed using multiple electronic databases (Ovid MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and the National Health Service Economic Evaluation Database) to identify relevant randomized trials and observational studies that evaluated statin adherence and/or persistence as an outcome. Eligible studies will include those involving community-living or outpatient elderly individuals. The methodological quality of randomized controlled trials (RCTs) will be assessed via the Joanna Briggs Institute's critical appraisal checklist for RCTs, and the quality assessment of observational studies will be undertaken using a set of questions formulated with resort to the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. When possible, meta-analyses will be conducted using random-effect modeling and generic inverse variance analyses for adjusted-effect estimates. Heterogeneity across studies will be quantified using the I2 statistic. The presence of publication bias will be assessed using funnel plots and Egger's regression tests. A leave-one-out sensitivity analysis will also be conducted to assess the impact of individual study results on pooled estimates. To explore possible sources of heterogeneity across studies, subgroup analyses will be performed based on covariates such as study design, statin indication, country of study, and length of patient follow-up.Results: The electronic database searches were completed in December 2016. Retrieved articles are currently being screened and the entire study is expected to be completed by June 2017.Conclusions: This systematic review will provide further understanding of the patterns of, and barriers to, statin adherence and persistence among older patients. The findings will inform clinical practice and the design of appropriate interventions

Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration