Impact of supervisors' research style on young biomedical scientists' capacity development as measured by REDi, a novel index of crossdisciplinarity.

The challenge for medical schools in Japan is to develop research activities for innovation. This study aimed at analyzing the connection between the research output of "promising researchers" (next-generation leaders in terms of research activity) and their supervisors' past research activities to identify those factors that impact researchers' performance. Activity was analyzed from the viewpoints of productivity, coauthorship networks, and research impact using a novel index called the Research Diversity Index (REDi) that quantifies crossdisciplinarity. Research funding, which has not yet been fully utilized in correlation studies of the characteristics of authors, was also considered in this study. For the promising researchers extracted using betweenness centrality scores within coauthorship networks, there were diachronic correlations between the records of the promising researchers and those of their supervisors. Supervisor leadership as measured by the number of last-authored publications and extent of networking had a positive effect on the promising researchers productivity. Supervisors' research style of integrating knowledge from multiple fields, as measured by REDi, was negatively correlated with the publication impact of promising researchers, suggesting that REDi is useful as a novel indicator of research quality not being captured by existing indices. It was also noted that establishing an academic presence through extensive collaborations could be advantageous for obtaining research funding, especially from top-down government programs. The possible implications of this study for promoting research activities are the importance of incorporating new doctorates into research groups at an early stage and that of promoting interinstitutional, crossdisciplinary collaborations. Classification code: MSC: 62P10 Applications of statistics to biology and medical sciences; meta-analysis.JEL: Z1Z10 Cultural Economics • Economic Sociology • Economic Anthropology- General.

The Remote Emerging Disease Intelligence-NETwork.

Accurate prediction of zoonotic spillover events requires a detailed understanding of baseline pathogens circulating in differing global environments. By characterizing the diversity and determining the natural baseline of pathogens in a given biological system, any perturbations to this balance can be detected, leading to estimates of risk for emerging diseases. As epidemics and probability for pandemics increase, there is a fundamental need for building global collaborations to fill gaps in the surveillance effort, especially to build remote in-county capacity and standardize timely sample processing and data analysis. To this point, a new consortium, the Remote Emerging Disease Intelligence-NETwork (REDI-NET) has been established to enhance surveillance approaches and characterize natural pathogens in temperate, tropical forest, and tropical grassland biomes. The REDI-NET is envisioned to be a long-term, phased initiative. All phases will integrate accompanying training resources such as videos reflecting SOPs and Quick Reference Guides. Routine bio- and xenosurveillance will facilitate the characterization of ecological parameters, enhance the accuracy of vector species identification using artificial intelligence technology, and guide the establishment of epidemiological risk thresholds critical for mitigating disease outbreaks in a timely manner. A key deliverable of the REDI-NET is a custom-designed electronically merged (e-MERGE) data pipeline and alert dashboard that integrates remotely captured data with state-of-the-art metagenomic next-generation sequencing technology. This pipeline incorporates data generated from field and laboratory best practices, to furnish health decision-makers with a centralized, timely, and rigorous database to efficiently search interdisciplinary and heterogeneous data sources necessary to alert, prepare and mitigate health threats. The e-MERGE pipeline, once fully established, will be a flexible, scalable, and expandable tool for varied health applications. Program success will result in an operational framework that addresses resource gaps in pathogen surveillance and enhances health protection with broad global applicability. The objective of this manuscript is to introduce the REDI-NET framework to anticipated stakeholders engaged in metagenomics, epidemiological surveillance, and One Health with a focus on Phase 1.

Does an Optimal Relationship Between Injury Risk and Workload Represented by the "Sweet Spot" Really Exist? An Example From Elite French Soccer Players and Pentathletes.

OBJECTIVE: To examine the relationships between the occurrence and severity of injuries using three workload ratios (ACWR, EWMA, REDI) in elite female soccer players and international male and female pentathletes. MATERIALS AND METHODS: Female soccer players in the U16 to U18 national French teams (n = 24) and international athletes (n = 12, 4 women and 8 men) in the French modern pentathlon team were monitored throughout an entire season. The Acute Chronic Workload Ratio (ACWR), the Exponentially Weighted Moving Averages (EWMA), and the Robust Exponential Decreasing Index (REDI) were calculated for internal load by the ROE method in soccer and external load in pentathlon. The occurrence and severity of injuries (determined according to time-loss) were quantified in the sweet spot zone [0.8; 1.3] and compared to the other zones of load variation: [0; 0.8], [1.3; 1.5], [1.5; +8], using the three ratios. RESULTS: Over the study period, a total of sixty-six injuries (2.75 per athlete) were reported in the soccer players and twelve in pentathletes (1 per athlete). The cumulative severity of all injuries was 788 days lost in soccer and 36 in pentathlon: respectively, 11.9 days lost per injury in soccer player and 3.0 per pentathlete. The mean values across the three methods in soccer showed a higher number of injuries detected in the [0; 0.8] workload ratio zone: 22.3 ± 6.4. They were 17.3 ± 3.5 in the sweet spot ([0.8-1.3] zone) and 17.6 ± 5.5 in the [1.5; +8] zone. In comparison to the [1.5; +8] zone, soccer players reported a higher number of days lost to injuries in the presumed sweet spot and in the [0-0.8] zone: 204.7 ± 28.7 and 275.0 ± 120.7 days, respectively. In pentathletes, ten of the twelve injuries (83.3%) occurred in the presumed sweet spot. REDI was the only method capable of tracking workloads over all-time series. CONCLUSION: In the present cohort of elite soccer players and pentathletes, acute chronic workload calculations showed an association with injury occurrence and severity but did not provide evidence supporting existence of a sweet spot diminishing injury risk.

US human factors engineering evaluation of an updated follitropin alfa pen injector (GONAL-f® RFF Redi-ject®) and instructions for use.

OBJECTIVES: The multi-dose, pre-filled GONAL-f® RFF Redi-ject® (follitropin alfa injection) pen injector was updated following feedback on user experience and pen functionality, as part of a continuous assessment program. Human-factors engineering (HFE) evaluations were conducted to confirm that the updated pen injector could be used by intended users to safely and effectively perform critical tasks identified by the risk-management plan. METHODS: Five rounds of formative evaluation and a simulated-use summative evaluation of the pen injector, instructions for use (IFU), and training video were conducted by HFE specialists or the intended users of the pen injector. RESULTS: The IFU and training video were revised following formative evaluations. Summative evaluation of simulated-use involved 60 participants, each of whom performed six use-scenarios related to potential hazards, selected on the basis of the risk-management plan. Overall, participants found the pen injector easy to use and the IFU clear and effective. CONCLUSIONS: Through an iterative process involving a series of HFE evaluations, modifications were made to the injection mechanism, the dose display, the IFU and the training video. Summative evaluation confirmed that the updated pen injector and associated user materials can be used safely and effectively to perform critical tasks identified through the risk-management plan.

Rapid Proteomics to Prospect and Validate Novel Bacterial Metabolism Induced by Environmental Burden.

Understanding the pathophysiology of genes and enzymes involved in caffeine metabolism can have extracurricular benefits, such as providing distinct methylxanthines as intermediates for pharmaceutical synthesis, and also improve environmental waste remediation. The strains Pseudomonas putida CBB5 and CES may provide insights into these applications because they may both be induced to degrade caffeine, yet the latter thrives in concentrations >8.0gL-1; threefold higher than any other bacteria. We took a novel approach toward identifying the enzymatic pathways in both Pseudomonas sp. CES and a deletion mutation of strain CBB5, which largely circumvented the need for exhaustive isolation of enzymes and the stepwise reconstitution of their activities to determine caffeine response elements. Here, we describe two optimized, rapid alternative strategies based on multiplexed SIL assays and demonstrate their application by discovering caffeine-degrading enzymes in the CES strain based on quantitative comparison between enriched lysate fractions drawn from bacterial proteomes grown in the absence and presence of caffeine. Comparisons were made using stable isotope dimethyl labeling and expression differences were substantiated by reciprocal labeling experiments. The role of the identified proteins in caffeine degradation was independently verified by genetic sequencing. Multiple new components of N-demethylase system were discovered within a fraction of the lysate enriched specifically for this activity. We also describe how to expand the biological context (and reduce systemic bias) by adapting the protocol for total lysate analysis. We combined off-line prefractionation with the speed and resolution advantages of the Orbitrap LUMOS. The global protocol revealed 2406 proteins 1789 of which were quantified between treatments revealing, among other insights, a new antagonistic degradation pathway for vanillin that is completely suppressed by caffeine treatment.

Generalizing Treatment Effect Estimates From Sample to Population: A Case Study in the Difficulties of Finding Sufficient Data.

BACKGROUND: Given increasing concerns about the relevance of research to policy and practice, there is growing interest in assessing and enhancing the external validity of randomized trials: determining how useful a given randomized trial is for informing a policy question for a specific target population. OBJECTIVES: This article highlights recent advances in assessing and enhancing external validity, with a focus on the data needed to make ex post statistical adjustments to enhance the applicability of experimental findings to populations potentially different from their study sample. RESEARCH DESIGN: We use a case study to illustrate how to generalize treatment effect estimates from a randomized trial sample to a target population, in particular comparing the sample of children in a randomized trial of a supplemental program for Head Start centers (the Research-Based, Developmentally Informed study) to the national population of children eligible for Head Start, as represented in the Head Start Impact Study. RESULTS: For this case study, common data elements between the trial sample and population were limited, making reliable generalization from the trial sample to the population challenging. CONCLUSIONS: To answer important questions about external validity, more publicly available data are needed. In addition, future studies should make an effort to collect measures similar to those in other data sets. Measure comparability between population data sets and randomized trials that use samples of convenience will greatly enhance the range of research and policy relevant questions that can be answered.

Rapid identification and quantitative validation of a caffeine-degrading pathway in Pseudomonas sp. CES.

Understanding the genes and enzymes involved in caffeine metabolism can lead to applications such as production of methylxanthines and environmental waste remediation. Pseudomonas sp. CES may provide insights into these applications, since this bacterium degrades caffeine and thrives in concentrations of caffeine that are three times higher (9.0 g L(-1)) than the maximum tolerable levels of other reported bacteria. We took a novel approach toward identifying the enzymatic pathways in Pseudomonas sp. CES that metabolize caffeine, which largely circumvented the need for exhaustive isolation of enzymes and the stepwise reconstitution of their activities. Here we describe an optimized, rapid alternative strategy based on multiplexed LC-MS/MS assays and show its application by discovering caffeine-degrading enzymes in the CES strain based on quantitative comparison of proteomes from bacteria grown in the absence and presence of caffeine, the latter condition of which was found to have a highly induced capacity for caffeine degradation. Comparisons were made using stable isotope dimethyl labeling, differences in the abundance of particular proteins were substantiated by reciprocal labeling experiments, and the role of the identified proteins in caffeine degradation was independently verified by genetic sequencing. Overall, multiple new components of a N-demethylase system were identified that resulted in rapid pathway validation and gene isolation using this new approach.

Flies from meat and wasps from trees: Reevaluating Francesco Redi's spontaneous generation experiments.

Francesco Redi's seventeenth-century experiments on insect generation are regarded as a key contribution to the downfall of belief in spontaneous generation. Scholars praise Redi for his experiments demonstrating that meat does not generate insects, but condemn him for his claim elsewhere that trees can generate wasps and gallflies. He has been charged with rejecting spontaneous generation only to change his mind and accept it, and in the process, with failing (at least in some sense) as a rigorous experimental philosopher. In this paper I defend Redi from both of these charges. In doing so, I draw some broader lessons for our understanding of spontaneous generation. 'Spontaneous generation' does not refer to a single theory, but rather a landscape of possible views. I analyze Redi's theoretical commitments and situate them within this landscape, and argue that his error in the case of insects from plants is not as problematic as previous commentators have said it is. In his research on gall insects Redi was addressing a different question from that of his experiments on insect generation-the question was not "Can insects come from nonliving matter?," but rather, "Can insects come from living organisms which are not their parents (namely, trees)?" In the latter case, he gave an answer which we now know to be false, but this was not due to any failure in his rigor as an experimental philosopher.