148 research outputs found

    Modeling Expert Opinions on Food Healthfulness: A Nutrition Metric

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    Research during the last several decades indicates the failure of existing nutritional labels to substantially improve the healthfulness of consumers\u27 food/beverage choices. The present study aims to fill this void by developing a nutrition metric that is more comprehensible to the average shopper. The healthfulness ratings of 205 sample foods/beverages by leading nutrition experts formed the basis for a linear regression that places weights on 12 nutritional components (ie, total fat, saturated fat, cholesterol, sodium, total carbohydrate, dietary fiber, sugars, protein, vitamin A, vitamin C, calcium, and iron) to predict the average healthfulness rating that experts would give to any food/beverage. Major benefits of the model include its basis in expert judgment, its straightforward application, the flexibility of transforming its output ratings to any linear scale, and its ease of interpretation. This metric serves the purpose of distilling expert knowledge into a form usable by consumers so that they are empowered to make more healthful decisions

    Defining and using microbial spectral databases

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    AbstractThis work shows how fingerprints of mass spectral patterns from microbial isolates are affected by variations in instrumental condition, by sample environment, and by sample handling factors. It describes a novel method by which pattern distortions can be mathematically corrected for variations in factors not amenable to experimental control. One uncontrollable variable is “between-batch” differences in culture media. Another, relevant for determination of noncultured extracts, is differences between the cells’ environmental experience (e.g., starved environmental extracts versus cultured standards). The method suggests that, after a single growth cycle on a solid medium (perhaps, a selective one), pyrolysis MS spectra of microbial isolates can be algorithmically compensated and an unknown isolate identified using a spectral database defined by culture on a different (perhaps, nonselective) medium. This reduces identification time to as few as 24 h from sample collection. The concept also proposes a possible way to compensate certain noncultured, nonisolated samples (e.g., cells concentrated from urine or impacted from aerosol or semi-selectively extracted by immunoaffinity methods from heavily contaminated matrices) for identification within half an hour. Using the method, microbial mass spectra from different labs can be assembled into coherent databases similar to those routinely used to identify pure compounds. This type of data treatment is applicable for rapid detection in biowarfare and bioterror events as well as in forensic, research, and clinical laboratory contexts

    AGN effect on cooling flow dynamics

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    We analyzed the feedback of AGN jets on cooling flow clusters using three-dimensional AMR hydrodynamic simulations. We studied the interaction of the jet with the intracluster medium and creation of low X-ray emission cavities (Bubbles) in cluster plasma. The distribution of energy input by the jet into the system was quantified in its different forms, i.e. internal, kinetic and potential. We find that the energy associated with the bubbles, (pV + gamma pV/(gamma-1)), accounts for less than 10 percent of the jet energy.Comment: "Accepted for publication in Astrophysics & Space Science

    Reducing publication delay to improve the efficiency and impact of conservation science.

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    Evidence-based decision-making is most effective with comprehensive access to scientific studies. If studies face significant publication delays or barriers, the useful information they contain may not reach decision-makers in a timely manner. This represents a potential problem for mission-oriented disciplines where access to the latest data is required to ensure effective actions are undertaken. We sought to analyse the severity of publication delay in conservation science-a field that requires urgent action to prevent the loss of biodiversity. We used the Conservation Evidence database to assess the length of publication delay (time from finishing data collection to publication) in the literature that tests the effectiveness of conservation interventions. From 7,447 peer-reviewed and non-peer-reviewed studies of conservation interventions published over eleven decades, we find that the raw mean publication delay was 3.2 years (±2SD = 0.1) and varied by conservation subject. A significantly shorter delay was observed for studies focused on Bee Conservation, Sustainable Aquaculture, Management of Captive Animals, Amphibian Conservation, and Control of Freshwater Invasive Species (Estimated Marginal Mean range from 1.4-1.9 years). Publication delay was significantly shorter for the non-peer-reviewed literature (Estimated Marginal Mean delay of 1.9 years ± 0.2) compared to the peer-reviewed literature (i.e., scientific journals; Estimated Marginal Mean delay of 3.0 years ± 0.1). We found publication delay has significantly increased over time (an increase of ~1.2 years from 1912 (1.4 years ± 0.2) to 2020 (2.6 years ± 0.1)), but this change was much weaker and non-significant post-2000s; we found no evidence for any decline. There was also no evidence that studies on more threatened species were subject to a shorter delay-indeed, the contrary was true for mammals, and to a lesser extent for birds. We suggest a range of possible ways in which scientists, funders, publishers, and practitioners can work together to reduce delays at each stage of the publication process

    Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial

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    Background Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. Methods Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. Results We cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08–6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39–7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. Conclusions Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally

    Immunoreactive trypsinogen levels in newborn screened infants with an inconclusive diagnosis of cystic fibrosis.

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    BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF. METHODS: In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016. RESULTS: Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8-206.2) vs. 75.0 (61.0-105.9); P \u3c 0.0001). Infants with CRMS/CFSPID→CF (n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3-126.8) vs. 73.7(60.0-96.0); P = 0.02). CONCLUSIONS: Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID

    Phenotypic characterization of virological failure following lopinavir/ritonavir monotherapy using full-length Gag-protease genes.

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    OBJECTIVES: Major protease mutations are rarely observed following first-line failure with PIs and interpretation of genotyping results in this context may be difficult. We performed extensive phenotyping of viruses from five patients failing lopinavir/ritonavir monotherapy in the MONARK study without major PI mutations by standard genotyping. METHODS: Phenotypic susceptibility testing and viral infectivity assessments were performed using a single-cycle assay and fold changes (FC) relative to a lopinavir-susceptible reference strain were calculated. RESULTS: >10-fold reduced baseline susceptibility to lopinavir occurred in two of five patients and >5-fold in another two. Four of five patients exhibited phylogenetic evidence of a limited viral evolution between baseline and failure, with amino acid changes at drug resistance-associated positions in one: T81A emerged in Gag with M36I in the protease gene, correlating with a reduction in lopinavir susceptibility from FC 7 (95% CI 6-8.35) to FC 13 (95% CI 8.11-17.8). Reductions in darunavir susceptibility (>5 FC) occurred in three individuals. DISCUSSION: This study suggests both baseline reduced susceptibility and evolution of resistance could be contributing factors to PI failure, despite the absence of classical PI resistance mutations by standard testing methods. Use of phenotyping also reveals lower darunavir susceptibility, warranting further study as this agent is commonly used following lopinavir failure

    Neural Systems Underlying RDoC Social Constructs: An Activation Likelihood Estimation Meta-Analysis

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    Neuroscientists have sought to identify the underlying neural systems supporting social processing that allow interaction and communication, forming social relationships, and navigating the social world. Through the use of NIMH’s Research Domain Criteria (RDoC) framework, we evaluated consensus among studies that examined brain activity during social tasks to elucidate regions comprising the “social brain”. We examined convergence across tasks corresponding to the four RDoC social constructs, including Affiliation and Attachment, Social Communication, Perception and Understanding of Self, and Perception and Understanding of Others. We performed a series of coordinate-based meta-analyses using the activation likelihood estimate (ALE) method. Meta-analysis was performed on whole-brain coordinates reported from 864 fMRI contrasts using the NiMARE Python package, revealing convergence in medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, temporoparietal junction, bilateral insula, amygdala, fusiform gyrus, precuneus, and thalamus. Additionally, four separate RDoC-based meta-analyses revealed differential convergence associated with the four social constructs. These outcomes highlight the neural support underlying these social constructs and inform future research on alterations among neurotypical and atypical populations
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