Spatially Explicit Data: Stewardship and Ethical Challenges in Science

Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration

Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Worldwide diagnostic reference levels for single-photon emission computed tomography myocardial perfusion imaging: findings from INCAPS.

OBJECTIVES: This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). BACKGROUND: Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. METHODS: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. RESULTS: The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m-labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. CONCLUSIONS: This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs

Resource Selection and Its Implications for Wide-Ranging Mammals of the Brazilian Cerrado

Conserving animals beyond protected areas is critical because even the largest reserves may be too small to maintain viable populations for many wide-ranging species. Identification of landscape features that will promote persistence of a diverse array of species is a high priority, particularly, for protected areas that reside in regions of otherwise extensive habitat loss. This is the case for Emas National Park, a small but important protected area located in the Brazilian Cerrado, the world's most biologically diverse savanna. Emas Park is a large-mammal global conservation priority area but is too small to protect wide-ranging mammals for the long-term and conserving these populations will depend on the landscape surrounding the park. We employed novel, noninvasive methods to determine the relative importance of resources found within the park, as well as identify landscape features that promote persistence of wide-ranging mammals outside reserve borders. We used scat detection dogs to survey for five large mammals of conservation concern: giant armadillo (Priodontes maximus), giant anteater (Myrmecophaga tridactyla), maned wolf (Chrysocyon brachyurus), jaguar (Panthera onca), and puma (Puma concolor). We estimated resource selection probability functions for each species from 1,572 scat locations and 434 giant armadillo burrow locations. Results indicate that giant armadillos and jaguars are highly selective of natural habitats, which makes both species sensitive to landscape change from agricultural development. Due to the high amount of such development outside of the Emas Park boundary, the park provides rare resource conditions that are particularly important for these two species. We also reveal that both woodland and forest vegetation remnants enable use of the agricultural landscape as a whole for maned wolves, pumas, and giant anteaters. We identify those features and their landscape compositions that should be prioritized for conservation, arguing that a multi-faceted approach is required to protect these species

Biophysical mechanisms of single-cell interactions with microtopographical cues

Biophysical cues encoded in the extracellular matrix (ECM) are increasingly being explored to control cell behavior in tissue engineering applications. Recently, we showed that cell adhesion to microtopographical structures (“micropegs”) can suppress proliferation in a manner that may be blunted by inhibiting cellular contractility, suggesting that this effect is related to altered cell-scaffold mechanotransduction. We now directly investigate this possibility at the microscale through a combination of live-cell imaging, single-cell mechanics methods, and analysis of gene expression. Using time-lapse imaging, we show that when cells break adhesive contacts with micropegs, they form F-actin-filled tethers that extend and then rupture at a maximum, critical length that is greater than trailing-edge tethers observed on topographically flat substrates. This critical tether length depends on myosin activation, with inhibition of Rho-associated kinase abolishing topography-dependent differences in tether length. Using cellular de-adhesion and atomic force microscopy indentation measurements, we show that the micropegs enhance cell-scaffold adhesive interactions without changing whole-cell elasticity. Moreover, micropeg adhesion increases expression of specific mechanotransductive genes, including RhoA GTPase and myosin heavy chain II, and, in myoblasts, the functional marker connexin 43. Together, our data support a model in which microtopographical cues alter the local mechanical microenvironment of cells by modulating adhesion and adhesion-dependent mechanotransductive signaling

Evaluating the sustainability, scalability, and replicability of an STH transmission interruption intervention: The DeWorm3 implementation science protocol.

Hybrid trials that include both clinical and implementation science outcomes are increasingly relevant for public health researchers that aim to rapidly translate study findings into evidence-based practice. The DeWorm3 Project is a series of hybrid trials testing the feasibility of interrupting the transmission of soil transmitted helminths (STH), while conducting implementation science research that contextualizes clinical research findings and provides guidance on opportunities to optimize delivery of STH interventions. The purpose of DeWorm3 implementation science studies is to ensure rapid and efficient translation of evidence into practice. DeWorm3 will use stakeholder mapping to identify individuals who influence or are influenced by school-based or community-wide mass drug administration (MDA) for STH and to evaluate network dynamics that may affect study outcomes and future policy development. Individual interviews and focus groups will generate the qualitative data needed to identify factors that shape, contextualize, and explain DeWorm3 trial outputs and outcomes. Structural readiness surveys will be used to evaluate the factors that drive health system readiness to implement novel interventions, such as community-wide MDA for STH, in order to target change management activities and identify opportunities for sustaining or scaling the intervention. Process mapping will be used to understand what aspects of the intervention are adaptable across heterogeneous implementation settings and to identify contextually-relevant modifiable bottlenecks that may be addressed to improve the intervention delivery process and to achieve intervention outputs. Lastly, intervention costs and incremental cost-effectiveness will be evaluated to compare the efficiency of community-wide MDA to standard-of-care targeted MDA both over the duration of the trial and over a longer elimination time horizon

Dysmorphometrics: the modelling of morphological abnormalities

<p>Abstract</p> <p>Background</p> <p>The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited.</p> <p>Methods</p> <p>A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram.</p> <p>Results</p> <p>We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities.</p> <p>Conclusion</p> <p>The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.</p