Digital Drugs: an anatomy of new medicines

Medicines are digitalized as aspects of their regulation and use are embodied in or draw from interlinked computerized systems and databases. This paper considers how this development changes the delivery of health care, the pharma industry, and regulatory and professional structures, as it reconfigures the material character of drugs themselves. It draws on the concept of assemblage in presenting a theory-based analysis that explores digital drugs’ ontological status including how they embody benefit and value. The paper addresses three interconnected domains – that of use of drugs (practice), of research (epistemology) and of regulation (structures)

Glucose-6-Phosphate Dehydrogenase Deficiency in an Endemic Area for Malaria in Manaus: A Cross-Sectional Survey in the Brazilian Amazon

BACKGROUND: There is a paucity of information regarding glucose-6-phosphate dehydrogenase (G6PD) deficiency in endemic areas for malaria in Latin America. METHODOLOGY/PRINCIPAL FINDINGS: This study determined the prevalence of the G6PD deficiency in 200 male non-consanguineous individuals residing in the Ismail Aziz Community, on the outskirts of Manaus (Brazilian Amazon). Six individuals (3%) were deficient using the qualitative Brewer's test. Gel electrophoresis showed that five of these patients were G6PD A(-). The deficiency was not associated with the ethnic origin (P = 0.571). In a multivariate logistic regression analysis, G6PD deficiency protected against three or more episodes of malaria (P = 0.049), independently of the age, and was associated with a history of jaundice (P = 0.020) and need of blood transfusion (P = 0.045) during previous treatment for malarial infection, independently of the age and the previous malarial exposure. CONCLUSIONS/SIGNIFICANCE: The frequency of G6PD deficiency was similar to other studies performed in Brazil and the finding of a predominant G6PD A(-) variant will help the clinical management of patients with drug-induced haemolysis. The history of jaundice and blood transfusion during previous malarial infection may trigger the screening of patients for G6PD deficiency. The apparent protection against multiple malarial infections in an area primarily endemic for Plasmodium vivax needs further investigation

Massively distributed authorship of academic papers

Wiki-like or crowdsourcing models of collaboration can provide a number of benefits to academic work. These techniques may engage expertise from different disciplines, and potentially increase productivity. This paper presents a model of massively distributed collaborative authorship of academic papers. This model, developed by a collective of thirty authors, identifies key tools and techniques that would be necessary or useful to the writing process. The process of collaboratively writing this paper was used to discover, negotiate, and document issues in massively authored scholarship. Our work provides the first extensive discussion of the experiential aspects of large-scale collaborative research.Peer ReviewedPostprint (author's final draft

Facing differences with an open mind: Openness to Experience, salience of intra-group differences, and performance of diverse groups.

This study examined how the performance of diverse teams is affected by member openness to experience and the extent to which team reward structure emphasizes intragroup differences. Fifty-eight heterogeneous four-person teams engaged in an interactive task. Teams in which reward structure converged with diversity (i.e., "faultline" teams) performed more poorly than teams in which reward structure cut across differences between group members or pointed to a "superordinate identity." High openness to experience positively influenced teams in which differences were salient (i.e., faultline and "cross-categorized" teams) but not teams with a superordinate identity. This effect was mediated by information elaboration

Process evaluation of a workplace-based health promotion and exercise cluster-randomised trial to increase productivity and reduce neck pain in office workers: A RE-AIM approach

© 2020 The Author(s). Background: This study uses the RE-AIM framework to provide a process evaluation of a workplace-based cluster randomised trial comparing an ergonomic plus exercise intervention to an ergonomic plus health promotion intervention; and to highlight variations across organisations; and consider the implications of the findings for intervention translation. Method: This study applied the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) methodology to examine the interventions' implementation and to explore the extent to which differences between participating organisations contributed to the variations in findings. Qualitative and quantitative data collected from individual participants, research team observations and organisations were interrogated to report on the five RE-AIM domains. Results: Overall reach was 22.7% but varied across organisations (range 9 to 83%). Participants were generally representative of the recruitment pool though more females (n = 452 or 59%) were recruited than were in the pool (49%). Effectiveness measures (health-related productivity loss and neck pain) varied across all organisations, with no clear pattern emerging to indicate the source of the variation. Organisation-level adoption (66%) and staffing level adoption (91%) were high. The interventions were implemented with minimal protocol variations and high staffing consistency, but organisations varied in their provision of resources (e.g. training space, seniority of liaisons). Mean adherence of participants to the EET intervention was 56% during the intervention period, but varied from 41 to 71% across organisations. At 12 months, 15% of participants reported regular EET adherence. Overall mean (SD) adherence to EHP was 56% (29%) across organisations during the intervention period (range 28 to 77%), with 62% of participants reporting regular adherence at 12 months. No organisations continued the interventions after the follow-up period. Conclusion: Although the study protocol was implemented with high consistency and fidelity, variations in four domains (reach, effectiveness, adoption and implementation) arose between the 14 participating organisations. These variations may be the source of mixed effectiveness across organisations. Factors known to increase the success of workplace interventions, such as strong management support, a visible commitment to employee wellbeing and participant engagement in intervention design should be considered and adequately measured for future interventions. Trial registration: ACTRN12612001154897; 29 October 2012

Comparative Omics-Driven Genome Annotation Refinement: Application across Yersiniae

Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. The annotation process is now performed almost exclusively in an automated fashion to balance the large number of sequences generated. One possible way of reducing errors inherent to automated computational annotations is to apply data from omics measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. Here, the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species. Transcriptomic and proteomic data derived from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 incorrect (i.e., observed frameshifts, extended start sites, and translated pseudogenes) protein-coding sequences within the three current genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent pathogen, thus the discovery of many translated pseudogenes, including the insertion-ablated argD, underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, a transcriptional regulator, and many hypothetical proteins that were missed during annotation

The Human Connectome Project's neuroimaging approach

Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease

Spin state behavior of iron(II)/dipyrazolylpyridine complexes. New insights from crystallographic and solution measurements

The isomeric complexes [Fe(1-bpp)2]2+ and [Fe(3-bpp)2]2+ (1-bpp=2,6-di[pyrazol-1-yl]pyridine; 3-bpp=2,6-di[1H-pyrazol-3-yl]pyridine) and their derivatives are some of the most widely investigated complexes in spin-crossover research. This article addresses two unique aspects of their spin-state chemistry. First, is an unusual structural distortion in the high-spin form that can inhibit spin-crossover in the solid state. A new analysis of these structures using continuous shape measures has explained this distortion in terms of its effect on the metal coordination geometry, and has shown that the most highly distorted structures are a consequence of crystal packing effects. Second, solution studies have quantified the influence of second-sphere hydrogen bonding on spin-crossover in [Fe(3-bpp)2]2+, which responds to the presence of different anions and solvents (especially water). Previously unpublished data from the unsymmetric isomer [Fe(1,3-bpp)2]2+ (1,3-bpp=2-[pyrazol-1-yl]-6-[1H-pyrazol-3-yl]pyridine) are presented for comparison. Modifications to the structure of [Fe(3-bpp)2]2+, intended to augment these supramolecular effects, are also described