Toward more rigorous and informative nutritional epidemiology: The rational space between dismissal and defense of the status quo.

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting-and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.

Boutiques: a flexible framework to integrate command-line applications in computing platforms.

We present Boutiques, a system to automatically publish, integrate, and execute command-line applications across computational platforms. Boutiques applications are installed through software containers described in a rich and flexible JSON language. A set of core tools facilitates the construction, validation, import, execution, and publishing of applications. Boutiques is currently supported by several distinct virtual research platforms, and it has been used to describe dozens of applications in the neuroinformatics domain. We expect Boutiques to improve the quality of application integration in computational platforms, to reduce redundancy of effort, to contribute to computational reproducibility, and to foster Open Science.

Reproducibility of neuroimaging analyses across operating systems.

Neuroimaging pipelines are known to generate different results depending on the computing platform where they are compiled and executed. We quantify these differences for brain tissue classification, fMRI analysis, and cortical thickness (CT) extraction, using three of the main neuroimaging packages (FSL, Freesurfer and CIVET) and different versions of GNU/Linux. We also identify some causes of these differences using library and system call interception. We find that these packages use mathematical functions based on single-precision floating-point arithmetic whose implementations in operating systems continue to evolve. While these differences have little or no impact on simple analysis pipelines such as brain extraction and cortical tissue classification, their accumulation creates important differences in longer pipelines such as subcortical tissue classification, fMRI analysis, and cortical thickness extraction. With FSL, most Dice coefficients between subcortical classifications obtained on different operating systems remain above 0.9, but values as low as 0.59 are observed. Independent component analyses (ICA) of fMRI data differ between operating systems in one third of the tested subjects, due to differences in motion correction. With Freesurfer and CIVET, in some brain regions we find an effect of build or operating system on cortical thickness. A first step to correct these reproducibility issues would be to use more precise representations of floating-point numbers in the critical sections of the pipelines. The numerical stability of pipelines should also be reviewed.

TLR4 signaling protects from excessive muscular damage induced by Bothrops jararacussu snake venom.

Immune cells and skeletal muscle express Toll-like receptors (TLRs) that participate as sensors of tissue injury triggering signals for activation of innate and adaptive immune responses. This study aimed to investigate the involvement of TLR4 in the process of skeletal muscle repair. Muscular injury was induced by injection of 0.6 mg/kg of Bothrops jararacussu snake venom in the gastrocnemius muscle of C3H/HeJ mice that express a non-functional TLR-4 receptor and C3H/HeN mice with functional receptor. TLR4-deficient mice had persistent muscular inflammation with few F4/80 macrophages at onset but increased MMP9 activity and collagen deposition during resolution of injury. Since such effect was not observed in the mouse strain with functional receptor it is concluded that TLR4 signaling exerts a protective role preventing from excessive muscular damage induced by B. jararacussu venom.