An evaluation of the performance of the Dynamiker® Fungus (1-3)-β-D-Glucan Assay to 2 assist in the diagnosis of Pneumocystis pneumonia

Invasive fungal disease (IFD) can be caused by a range of pathogens. Conventional diagnosis has the capacity to detect most causes of IFD, but poor performance limits impact. The introduction of non-culture diagnostics, including the detection of (1-3)-β-D-Glucan (BDG), has shown promising performance for the detection of IFD in variety of clinical settings. Recently, the Dynamiker® Fungus (1-3)-β-D-Glucan assay (D-BDG) was released as an IFD diagnostic test. This article describes an evaluation of the D-BDG assay for the diagnosis of invasive aspergillosis (IA), invasive candidiasis (IC) and Pneumocystis pneumonia (PCP) across several high-risk patient cohorts and provides comparative data with the Associates of Cape Cod Fungitell® and BioRad Platelia™ Aspergillus Ag (GM) assays. There were 163 serum samples from 121 patients tested, from 21 probable IA cases, 28 proven IC cases, six probable PCP cases, one probable IFD case, 14 possible IFD cases and 64 control patients. For proven/probable IFD the mean BDG concentration was 209pg/ml, significantly greater than the control population (73pg/ml; P: <.0001). The sensitivity, specificity, and diagnostic odds ratio for proven/probable IFD was 81.4%, 78.1%, and 15.5, respectively. Significant BDG false positivity (9/13) was associated post abdominal surgery. D-BDG showed fair and good agreement with the Fungitell®, and GM assays, respectively. In conclusion, the D-BDG provides a useful adjunct test to aid the diagnosis of IFD, with technical flexibility that will assist laboratories processing low sample numbers. Further, large scale, prospective evaluation is required to confirm the clinical validity and determine clinical utility

Peanut Performance and Weed Management in a High-residue Cover Crop System

Previous research has indicated that conservation tillage is a viable option for successful peanut production; however, interactions between cover crop residues and peanut growth are not fully understood. Additional information is needed about the effects of varying levels of cover crop biomass on peanut growth and development. Level of cover crop residue may also affect the preemergence herbicide activity through interception and efficacy of weed suppression. The objectives of this peanut research were to determine if varying amounts of cover crop biomass would affect peanut growth, herbicide interception, or weed control. This research also aimed to determine if cover crop management practices (rolling or standing cover) would affect herbicide interception rates. The study consisted of a rye (Secale cereale L.) cover crop planted at three different dates as well as a fallow treatment at two locations: Dawson, GA, and Headland, AL. Pendimethalin was applied PRE at 1 kg ai/ha across the entire area just prior to planting of the Georgia 03-L peanut variety. Soil samples were collected at three different dates after planting for high-pressure liquid chromatography (HPLC) analysis to determine pendimethalin levels. Peanut yields differed only between location regardless of cover crop residue level with the Headland, Alabama, site averaging 4,272 kg/ha and the Dawson, Georgia, site averaging 2,247 kg/ha. Pendimethalin extraction from soil samples indicated no difference in herbicide recovery between winter fallow systems compared to treatments with cover crops. Weed control ratings taken at 21 and 45 days after planting (DAP) showed greater weed suppression for cover crop systems for an extended period of time when higher levels of cover crop biomass are present. Results of this experiment indicate the inclusion of cover crops in a conservation-tilled peanut system can be a successful alternative to winter fallow systems without reducing peanut yield or herbicide efficacy

Organic Weed Control and Cover Crop Residue Integration Impacts on Weed Control, Quality, Yield and Economics in Conservation Tillage Tomato-A Case Study

The increased adoption of conservation tillage and organic weed control practices in vegetable production requires more information on the role of various cover crops in integrated weed control, tomato quality, and yield. Two conservation-tillage systems utilizing crimson clover and cereal rye as winter cover crops were compared to a conventional black polythene mulch system, with or without organic weed management options, for weed control, tomato yield, and profitability. All cover crops were terminated with a mechanical roller/crimper prior to planting. Organic weed control treatments included: 1) flaming utilizing a one burner hand torch, 2) PRE application of corn gluten, 3) PRE application of corn gluten followed by flaming, or 4) intermittent hand weeding as needed. A non-treated control and a standard herbicide program were included for comparison. The herbicide program consisting of a PRE application of S-metolachlor (1.87 kg a.i./ha) followed by an early POST metribuzin (0.56 kg a.i. /ha) application followed by a late POST application of clethodim (0.28 kg a.i./ha). In general, high-residue clover and cereal rye cover crops provided substantial suppression of Palmer amaranth, large crabgrass, and yellow nutsedge. Across systems, minimum input in high-residue systems provided the highest net returns above variable costs compared to organic herbicide treatments that are costly and provide marginal benefit

Public health training in internal medicine residency programs: a national survey

BACKGROUND: The IOM recommends public health training for all physicians. Data characterizing such training of internal medicine (IM) residents are lacking. PURPOSE: To describe the current state of public health education at IM residency programs, characterize programs offering public health education, and quantify interest in expanding training opportunities. METHODS: IM residency program directors from the 380 Accreditation Council for Graduate Medical Education-accredited residency programs in the U.S were invited to participate in a cross-sectional survey. Responses were received from 127 programs (33%). Data were collected July-December 2012 and analyzed in January 2013. Participants were queried on domestic public health training offered, perceived resident interest in and satisfaction with this training, and interest in expanding training. RESULTS: Eighty-four respondents (66%) provide some form of public health training, but structure and content vary widely. In many programs offering public health training, few residents (\u3c10%) receive it. Although 93 programs (73%) integrate public health into core curricula, only three topics were common to a majority of these programs. Sixty-six respondents (52%) offer clinical training at community-based health centers. Most residency program directors (90%) are very or somewhat interested in expanding their public health training. CONCLUSIONS: This study characterizes the structures and content of public health training across IM residency programs. The wide range highlights the diverse definition of public health training used by IM residency program directors and lack of universal public health competencies required for IM physicians. Opportunities exist for collaboration among residency programs and between IM and public health educators to share best practices

Likelihood-ratio ranking of gravitational-wave candidates in a non-Gaussian background

We describe a general approach to detection of transient gravitational-wave signals in the presence of non-Gaussian background noise. We prove that under quite general conditions, the ratio of the likelihood of observed data to contain a signal to the likelihood of it being a noise fluctuation provides optimal ranking for the candidate events found in an experiment. The likelihood-ratio ranking allows us to combine different kinds of data into a single analysis. We apply the general framework to the problem of unifying the results of independent experiments and the problem of accounting for non-Gaussian artifacts in the searches for gravitational waves from compact binary coalescence in LIGO data. We show analytically and confirm through simulations that in both cases the likelihood ratio statistic results in an improved analysis.Comment: 10 pages, 6 figure

Taking the next-gen step: Comprehensive antimicrobial resistance detection from Burkholderia pseudomallei

Background: Antimicrobial resistance (AMR) poses a major threat to human health. Whole-genome sequencing holds great potential for AMR identification; however, there remain major gaps in accurately and comprehensively detecting AMR across the spectrum of AMR-conferring determinants and pathogens. Methods: Using 16 wild-type Burkholderia pseudomallei and 25 with acquired AMR, we first assessed the performance of existing AMR software (ARIBA, CARD, ResFinder, and AMRFinderPlus) for detecting clinically relevant AMR in this pathogen. B. pseudomallei was chosen due to limited treatment options, high fatality rate, and AMR caused exclusively by chromosomal mutation (i.e. single-nucleotide polymorphisms [SNPs], insertions-deletions [indels], copy-number variations [CNVs], inversions, and functional gene loss). Due to poor performance with existing tools, we developed ARDaP (Antimicrobial Resistance Detection and Prediction) to identify the spectrum of AMR-conferring determinants in B. pseudomallei. Findings: CARD, ResFinder, and AMRFinderPlus failed to identify any clinically-relevant AMR in B. pseudomallei; ARIBA identified AMR encoded by SNPs and indels that were manually added to its database. However, none of these tools identified CNV, inversion, or gene loss determinants, and ARIBA could not differentiate AMR determinants from natural genetic variation. In contrast, ARDaP accurately detected all SNP, indel, CNV, inversion, and gene loss AMR determinants described in B. pseudomallei (n≈50). Additionally, ARDaP accurately predicted three previously undescribed determinants. In mixed strain data, ARDaP identified AMR to as low as ~5% allelic frequency. Interpretation: Existing AMR software packages are inadequate for chromosomal AMR detection due to an inability to detect resistance conferred by CNVs, inversions, and functional gene loss. ARDaP overcomes these major shortcomings. Further, ARDaP enables AMR prediction from mixed sequence data down to 5% allelic frequency, and can differentiate natural genetic variation from AMR determinants. ARDaP databases can be constructed for any microbial species of interest for comprehensive AMR detection

Compound Ranking Based on a New Mathematical Measure of Effectiveness Using Time Course Data from Cell-Based Assays

The half maximal inhibitory concentration (IC50) has several limitations that make it unsuitable for examining a large number of compounds in cytotoxicity studies, particularly when multiple exposure periods are tested. This article proposes a new approach to measure drug effectiveness, which allows ranking compounds according to their toxic effects on live cells. This effectiveness measure, which combines all exposure times tested, compares the growth rates of a particular cell line in the presence of the compound with its growth rate in the presence of DMSO alone. Our approach allows measuring a wider spectrum of toxicity than the IC50 approach, and allows automatic analyses of a large number of compounds. It can be easily implemented in linear regression software, provides a comparable measure of effectiveness for each investigated compound (both toxic and non-toxic), and allows statistically testing the null hypothesis that a compound is non-toxic versus the alternative that it is toxic. Importantly, our approach allows defining an automated decision rule for deciding whether a compound is significantly toxic. As an illustration, we describe the results of a cell-based study of the cytotoxicity of 24 analogs of novobiocin, a C-terminal inhibitor of heat shock protein 90 (Hsp90); the compounds were ranked in order of cytotoxicity to a panel of 18 cancer cell lines and 1 normal cell line. Our approach may also be a good alternative to computing the half maximal effective concentration (EC50) in studies searching for compounds that promote cell growth

Pathways into services for offenders with intellectual disabilities : childhood experience, diagnostic information and offence variables

The patterns and pathways into intellectual disability (ID) offender services were studied through case file review for 477 participants referred in one calendar year to community generic, community forensic, and low, medium, and maximum secure services. Data were gathered on referral source, demographic information, index behavior, prior problem behaviors, diagnostic information, and abuse or deprivation. Community referrers tended to refer to community services and secure service referrers to secure services. Physical and verbal violence were the most frequent index behaviors, whereas contact sexual offenses were more prominent in maximum security. Age at first incident varied with security, with the youngest in maximum secure services. Attention-deficit/hyperactivity disorder or conduct disorder was the most frequently recorded diagnosis, and severe deprivation was the most frequent adverse developmental experience. Fire starting, theft, and road traffic offenses did not feature prominently. Generic community services accepted a number of referrals with forensic-type behavior and had higher proportions of both women and people with moderate or severe ID

Enhancement and suppression effects resulting from information structuring in sentences

Information structuring through the use of cleft sentences increases the processing efficiency of references to elements within the scope of focus. Furthermore, there is evidence that putting certain types of emphasis on individual words not only enhances their subsequent processing, but also protects these words from becoming suppressed in the wake of subsequent information, suggesting mechanisms of enhancement and suppression. In Experiment 1, we showed that clefted constructions facilitate the integration of subsequent sentences that make reference to elements within the scope of focus, and that they decrease the efficiency with reference to elements outside of the scope of focus. In Experiment 2, using an auditory text-change-detection paradigm, we showed that focus has similar effects on the strength of memory representations. These results add to the evidence for enhancement and suppression as mechanisms of sentence processing and clarify that the effects occur within sentences having a marked focus structure