1,101 research outputs found

    Post hoc support vector machine learning for impedimetric biosensors based on weak protein-ligand interactions

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    Impedimetric biosensors for measuring small molecules based on weak/transient interactions between bioreceptor and target analyte are a challenge for detection electronics, particularly in field studies or in analysis of complex matrices. Protein-ligand binding sensors have enormous potential for biosensing, but accuracy in complex solutions is a major challenge. There is a need for simple post hoc analytical tools that are not computationally expensive, yet provide near real time feedback on data derived from impedance spectra. Here, we show use of a simple, open source support vector machine learning algorithm for analyzing impedimetric data in lieu of using equivalent circuit analysis. We demonstrte two different protein-based biosensors to show that the tool can be used for various applications. We conclude with a mobile phone-based demonstration focused on measurement of acetone, an important biomarker related to onset of diabetic ketoacidosis. In all conditions tested, the open source classifier was capable of performing as well, or better, than equivalent circuit analysis for characterizing weak/transient interactions between a model ligand (acetone) and a small chemosensory protein derived from tsetse fly. In addition, the tool has a low computational requirement, facilitating use for mobile acquisition systems such as mobile phone. The protocol is deployed through Jupyter notebook (an open source computing environment available for mobile phone, tablet, or computer use) and the code was written in Python. For each of the applications we provide step-by-step instructions in English, Spanish, Mandarin, and Portuguese to facilitate widespread use. All codes were based on scikit-learn, an open source software machine learning library in the Python language, and were processed in Jupyter notebook, an open-source web application for Python. The tool can easily be integrated with mobile biosensor equipment for rapid detection, facilitating use by a broad range of impedimetric biosensor users. This post hoc analysis tool can serve as a launchpad for convergence of nanobiosensors in planetary health monitoring applications based on mobile phone hardware

    Assessment of Adolescents’ Victimization, Aggression, and Problem Behaviors: Evaluation of the Problem Behavior Frequency Scale

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    This study evaluated the Problem Behavior Frequency Scale (PBFS), a self-report measure designed to assess adolescents’ frequency of victimization, aggression, and other problem behaviors. Analyses were conducted on a sample of 5,532 adolescents from 37 schools at 4 sites. About half (49%) of participants were male; 48% self-identified as Black non-Hispanic; 21% as Hispanic, 18% as White non-Hispanic. Adolescents completed the PBFS and measures of beliefs and values related to aggression, and delinquent peer associations at the start of the 6th grade and over 2 years later. Ratings of participants’ behavior were also obtained from teachers on the Behavioral Assessment System for Children. Confirmatory factor analyses supported a 7-factor model that differentiated among 3 forms of aggression (physical, verbal, and relational), 2 forms of victimization (overt and relational), drug use, and other delinquent behavior. Support was found for strong measurement invariance across gender, sites, and time. The PBFS factors generally showed the expected pattern of correlations with teacher ratings of adolescents’ behavior and self-report measures of relevant constructs

    Seroprevalence of Pandemic Influenza H1N1 in Ontario from January 2009–May 2010

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    We designed a seroprevalence study using multiple testing assays and population sources to estimate the community seroprevalence of pH1N1/09 and risk factors for infection before the outbreak was recognized and throughout the pandemic to the end of 2009/10 influenza season.Residual serum specimens from five time points (between 01/2009 and 05/2010) and samples from two time points from a prospectively recruited cohort were included. The distribution of risk factors was explored in multivariate adjusted analyses using logistic regression among the cohort. Antibody levels were measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays.Residual sera from 3375 patients and 1024 prospectively recruited cohort participants were analyzed. Pre-pandemic seroprevalence ranged from 2%-12% across age groups. Overall seropositivity ranged from 10%-19% post-first wave and 32%-41% by the end of the 2009/10 influenza season. Seroprevalence and risk factors differed between MN and HAI assays, particularly in older age groups and between waves. Following the H1N1 vaccination program, higher GMT were noted among vaccinated individuals. Overall, 20-30% of the population was estimated to be infected.Combining population sources of sera across five time points with prospectively collected epidemiological information yielded a complete description of the evolution of pH1N1 infection

    Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study.

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    BACKGROUND: CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. MATERIALS AND METHODS: Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. RESULTS: The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1-59.9) weeks for skin sTRAEs to 47.6 (47.1-48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1-123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1-79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. CONCLUSION: Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment. IMPLICATIONS FOR PRACTICE: Nivolumab is a viable treatment option for patients with previously treated advanced hepatocellular carcinoma as it has demonstrated durable tumor responses and promising survival. Nivolumab has a manageable safety profile. The most common select treatment-related adverse events (sTRAEs) in this analysis were skin related (35%). Gastrointestinal and hepatic sTRAEs were observed in approximately 14% of patients. The majority of sTRAEs resolved (68%). Safety events are easier to manage if addressed early. Patient education on signs and symptoms to watch out for and the importance of early reporting and consultation should be emphasized

    Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

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    BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

    Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study

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    Background. CheckMate 040 assessed the efficacy and safety of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is needed to support the management of treatment-related adverse events (TRAEs). This analysis assessed the safety of nivolumab monotherapy in the phase I/II, open-label CheckMate 040 study. Materials and Methods. Select TRAEs (sTRAEs; TRAEs with potential immunologic etiology requiring more frequent monitoring) occurring between first dose and 30 days after last dose were analyzed in patients in the dose-escalation and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and the outcome of treatment with immune-modulating medication (IMM) was evaluated. Results. The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal (14.5%) and hepatic (14.1%) events; the majority were grade 1/2, with 10.7% of patients experiencing grade 3/4 events. One patient had grade 5 pneumonitis. Median (range) TTO ranged from 3.6 (0.1–59.9) weeks for skin sTRAEs to 47.6 (47.1–48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs resolved, with median (range) TTR ranging from 3.7 (0.1–123.3+) weeks for gastrointestinal sTRAEs to 28.4 (0.1–79.1) weeks for endocrine sTRAEs. Most gastrointestinal and all hepatic events resolved with treatment in accordance with established toxicity management algorithms. In 57 patients (40%), sTRAEs were managed with IMM. Reoccurrence of sTRAEs was uncommon following rechallenge with nivolumab. Conclusion. Nivolumab demonstrated a manageable safety profile in this analysis of patients with advanced HCC. A majority of sTRAEs resolved with treatment

    Quantifying Excess Deaths Related to Heatwaves under Climate Change Scenarios: A multicountry time series modelling study

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    Background: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited. Methods and findings: We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave–mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971–2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031–2080 compared with 1971–2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections. Conclusions: This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change. © 2018 Guo et al. http://creativecommons.org/licenses/by/4.0/
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