Pluggable type-checking for custom type qualifiers in Java

We have created a framework for adding custom type qualifiers to the Javalanguage in a backward-compatible way. The type system designer definesthe qualifiers and creates a compiler plug-in that enforces theirsemantics. Programmers can write the type qualifiers in their programs andbe informed of errors or assured that the program is free of those errors.The system builds on existing Java tools and APIs.In order to evaluate our framework, we have written four type-checkersusing the framework: for a non-null type system that can detect andprevent null pointer errors; for an interned type system that can detectand prevent equality-checking errors; for a reference immutability typesystem, Javari, that can detect and prevent mutation errors; and for areference and object immutability type system, IGJ, that can detect andprevent even more mutation errors. We have conducted case studies usingeach checker to find real errors in existing software. These case studiesdemonstrate that the checkers and the framework are practical and useful

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Introduction: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods: A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results: 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions: Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration: International Standard Randomized Control Trial Registry ISRCTN64637517

Mitoquinone (mitoQ) Exerts Antioxidant Effects Independent of Mitochondrial Targeted Effects in Phorbol-12-myristate-13-acetate (PMA) or N-formyl-L-methiony-L-leucyl-L-phenylalanine (fMLP) Stimulated Polymorphonuclear Leukocyte (PMN) Superoxide (SO) Release

MitoQ is a mitochondrial-targeted coenzyme Q antioxidant analog that dose-dependently restored cardiac function and reduced infarct size in isolated perfused rat hearts subjected to ischemia reperfusion (I/R). Moreover, mitoQ also dose-dependently attenuated PMA stimulated PMN superoxide (SO) release at the same concentration (10uM) as the cardioprotective dose. NADPH oxidase is the principle source of PMN SO release. We speculate that mitoQ may exert antioxidant effects independent of the mitochondria. Therefore, we hypothesized that inhibition of mitoQ on PMN-SO release will be similar as other coenzyme Q analogs: coenzyme Q1 and decylubiquinone without affecting cell viability. SO release was measured spectrophotometrically from isolated rat PMNs measured by the reduction of ferricytochrome c and were stimulated with 100nM PMA. The absorbance was measured at 550 nm up to 360sec. Positive control samples were given SO dismutase (SOD; 10ug/ml) which inhibited PMA induced SO release by \u3e90%. MitoQ significantly inhibited SO release by 56 + 3% (10uM, n=10 ,

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Advances in transposable elements: from mechanisms to applications in mammalian genomics

It has been 70 years since Barbara McClintock discovered transposable elements (TE), and the mechanistic studies and functional applications of transposable elements have been at the forefront of life science research. As an essential part of the genome, TEs have been discovered in most species of prokaryotes and eukaryotes, and the relative proportion of the total genetic sequence they comprise gradually increases with the expansion of the genome. In humans, TEs account for about 40% of the genome and are deeply involved in gene regulation, chromosome structure maintenance, inflammatory response, and the etiology of genetic and non-genetic diseases. In-depth functional studies of TEs in mammalian cells and the human body have led to a greater understanding of these fundamental biological processes. At the same time, as a potent mutagen and efficient genome editing tool, TEs have been transformed into biological tools critical for developing new techniques. By controlling the random insertion of TEs into the genome to change the phenotype in cells and model organisms, critical proteins of many diseases have been systematically identified. Exploiting the TE’s highly efficient in vitro insertion activity has driven the development of cutting-edge sequencing technologies. Recently, a new technology combining CRISPR with TEs was reported, which provides a novel targeted insertion system to both academia and industry. We suggest that interrogating biological processes that generally depend on the actions of TEs with TEs-derived genetic tools is a very efficient strategy. For example, excessive activation of TEs is an essential factor in the occurrence of cancer in humans. As potent mutagens, TEs have also been used to unravel the key regulatory elements and mechanisms of carcinogenesis. Through this review, we aim to effectively combine the traditional views of TEs with recent research progress, systematically link the mechanistic discoveries of TEs with the technological developments of TE-based tools, and provide a comprehensive approach and understanding for researchers in different fields

Evaluation of Coach-Based Technical Assistance: An Evolving Focus on Coachability and Goal Setting

In 2013, the National Institute of Food and Agriculture supported the creation of a professional development and technical assistance center to promote strong implementation and evaluation of University-led, community-based projects serving low-resource populations. Within this center, a coaching cadre was established to provide proactive and responsive technical assistance. Formative evaluation involving coaches and their primary contacts was used for refinement of coaching practices. Initially, coaches were encouraged to build strong interpersonal rapport. This set the stage for trusting, reciprocal interactions, but coaches recognized a need for targeted support and more tools for quality programming, evaluation, and sustainability. Greater emphasis was placed on goal-focused collaboration. Coaches received training and resources on topics such as goal setting, program quality, reduction of barriers (e.g., participant recruitment), and sustainability strategies. To assess coaching model enhancements, a survey of projects was expanded to gauge logic model usage, goal setting, strength of coaching relationships, and project implementation and sustainability progress. Overall, coaching was rated more favorably and effective when contact was consistent, inclusive of face-to-face interaction, met technical needs, and involved collaborative brainstorming and planning. Findings indicate coaching relationships strengthen over time and demand a collaborative, action-orientation to set goals, reduce barriers, and drive stronger outcomes

Preparing for the spread of patient-reported outcomes (PROs) data collection from primary care to community pharmacy: stakeholder insights

Medication non-adherence is a significant public health problem. Patient-reported outcomes (PROs) offer a rich data source to facilitate resolution of medication non-adherence. PatientToc™ is an electronic PRO data collection software originally implemented at primary care practices in California, United States (US). Currently, the use of standardized PRO data collection systems in US community pharmacies is limited. Thus, we are conducting a two-phase evaluation of the spread and scale of PatientToc™ to US Midwestern community pharmacies. This report focuses on the first phase of the evaluation. The objective of this phase was to prepare for implementation of PatientToc™ in community pharmacies by conducting a pre-implementation developmental formative evaluation to (1) identify potential barriers, facilitators, and actionable recommendations to PatientToc™ implementation and (2) create a draft implementation toolkit