‘I like to run to feel’: Embodiment and wearable mobile tracking devices in distance running

Many experienced runners consider the use of wearable devices an important element of the training process. A key techno-utopic promise of wearables lies in the use of proprietary algorithms to identify training load errors in real-time and alert users to risks of running-related injuries. Such real-time ‘knowing’ is claimed to obviate the need for athletes’ subjective judgements by telling runners how they have deviated from a desired or optimal training load or intensity. This realist-contoured perspective is, however, at odds with sociological research indicating that users of wearables engage in active ‘data sense-making’ that is highly contextualised. To investigate how athletes use (or not) algorithmic analysis to understand, make sense of, and improve their performance in real-time, we undertook qualitative interviews with distance runners to explore lived experiences of running with wearables. The runners described how they actively interpreted data from wearables, drawing on their own experience, ‘somatic knowledge’, and embodied ways of knowing. This allowed them to assess the relevance and usefulness of data in relation to their own goals, intentions, and feelings. Our findings challenge the techno-utopic promises of real-time and predictive analytics

Dopamine D2 receptor gene variants and response to rasagiline in early Parkinson's disease:a pharmacogenetic study

The treatment of early Parkinson's disease with dopaminergic agents remains the mainstay of symptomatic therapy for this incurable neurodegenerative disorder. However, clinical responses to dopaminergic drugs vary substantially from person to person due to individual-, drug- and disease-related factors that may in part be genetically determined. Using clinical data and DNA samples ascertained through the largest placebo-controlled clinical trial of the monoamine oxidase B inhibitor, rasagiline (ClinicalTrials.gov number, NCT00256204), we examined how polymorphisms in candidate genes associate with the clinical response to rasagiline in early Parkinson's disease. Variants in genes that express proteins involved in the pharmacokinetics and pharmacodynamics of rasagiline, and genes previously associated with the risk to develop Parkinson's disease were genotyped. The LifeTechnologies OpenArray NT genotyping platform and polymerase chain reaction-based methods were used to analyse 204 single nucleotide polymorphisms and five variable number tandem repeats from 30 candidate genes in 692 available DNA samples from this clinical trial. The peak symptomatic response to rasagiline, the rate of symptom progression, and their relation to genetic variation were examined controlling for placebo effects using general linear and mixed effects models, respectively. Single nucleotide polymorphisms, rs2283265 and rs1076560, in the dopamine D2 receptor gene (DRD2) were found to be significantly associated with a favourable peak response to rasagiline at 12 weeks in early Parkinson's disease after controlling for multiple testing. From a linear regression, the betas were 2.5 and 2.38, respectively, with false discovery rate-corrected P-values of 0.032. These polymorphisms were in high linkage disequilibrium with each other (r(2) = 0.96) meaning that the same clinical response signal was identified by each of them. No polymorphisms were associated with slowing the rate of worsening in Parkinson symptoms from Weeks 12 to 36 after correction for multiple testing. This is the largest and most comprehensive pharmacogenetics study to date examining clinical response to an anti-parkinsonian drug and the first to be conducted in patients with early stage Parkinson's disease receiving monotherapy. The results indicate a clinically meaningful benefit to rasagiline in terms of the magnitude of improvement in parkinsonian symptoms for those with the favourable response genotypes. Future work is needed to elucidate the specific mechanisms through which these DRD2 variants operate in modulating the function of the nigrostriatal dopaminergic system

The prevalence of scabies in Monrovia, Liberia: A population-based survey.

Scabies is known to be a public health problem in many settings but the majority of recent data is from rural settings in the Pacific. There is a need for high quality data from sub-Saharan Africa and peri-urban settings to inform scale up of scabies control efforts. There have been anecdotal reports of scabies being a public health problem in Liberia but robust data are lacking. We conducted a cross-sectional cluster-randomised prevalence survey for scabies in a peri-urban community in Monrovia, Liberia in February-March 2020. Participants underwent a standardised examination conducted by trained local health care workers. Health related quality of life (HRQoL) was assessed using age-appropriate versions of the dermatology life quality index (DLQI). Prevalence estimates were calculated accounting for clustering at community and household levels and associations with key demographic variables assessed through multivariable random-effects logistic regression. 1,318 participants from 477 households were surveyed. The prevalence of scabies was 9.3% (95% CI: 6.5-13.2%), across 75 (19.7%) households; impetigo or infected scabies prevalence was 0.8% (95% CI: 0.4-1.9%). The majority (52%) of scabies cases were classified as severe. Scabies prevalence was lower in females and higher in the youngest age group; no associations were found with other collected demographic or socio-economic variables. DLQI scores indicated a very or extremely large effect on HRQoL in 29% of adults and 18% of children diagnosed with scabies. Our study indicates a substantial burden of scabies in this peri-urban population in Liberia. This was associated with significant impact on quality of life, highlighting the need for action to control scabies in this population. Further work is needed to assess the impact of interventions in this context on both the prevalence of scabies and quality of life

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Methods: Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed. Results: A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Conclusions: Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered

Dual Electron Spectrometer for Magnetospheric Multiscale Mission: Results of the Comprehensive Tests of the Engineering Test Unit

The Magnetospheric Multiscale mission (MMS) is designed to study fundamental phenomena in space plasma physics such as a magnetic reconnection. The mission consists of four spacecraft, equipped with identical scientific payloads, allowing for the first measurements of fast dynamics in the critical electron diffusion region where magnetic reconnection occurs and charged particles are demagnetized. The MMS orbit is optimized to ensure the spacecraft spend extended periods of time in locations where reconnection is known to occur: at the dayside magnetopause and in the magnetotail. In order to resolve fine structures of the three dimensional electron distributions in the diffusion region (reconnection site), the Fast Plasma Investigation's (FPI) Dual Electron Spectrometer (DES) is designed to measure three dimensional electron velocity distributions with an extremely high time resolution of 30 ms. In order to achieve this unprecedented sampling rate, four dual spectrometers, each sampling 180 x 45 degree sections of the sky, are installed on each spacecraft. We present results of the comprehensive tests performed on the DES Engineering & Test Unit (ETU). This includes main parameters of the spectrometer such as energy resolution, angular acceptance, and geometric factor along with their variations over the 16 pixels spanning the 180-degree tophat Electro Static Analyzer (ESA) field of view and over the energy of the test beam. A newly developed method for precisely defining the operational space of the instrument is presented as well. This allows optimization of the trade-off between pixel to pixel crosstalk and uniformity of the main spectrometer parameters

Citizen science breathes new life into participatory agricultural research : A review

Participatory research can improve the efficiency, effectiveness, and scope of research processes, and foster social inclusion, empowerment and sustainability. Yet despite four decades of agricultural research institutions exploring and developing methods for participatory research, it has never become mainstream in the agricultural technology development cycle. Citizen science promises an innovative approach to participation in research, using the unique facilities of new digital technologies, but its potential in agricultural research participation has not been systematically probed. To this end, we conducted a critical literature review. We found that citizen science opens up four opportunities for creatively reshaping research: i) new possibilities for interdisciplinary collaboration, ii) rethinking configurations of socio-computational systems, iii) research on democratization of science more broadly, and iv) new accountabilities. Citizen science also brings a fresh perspective on the barriers to institutionalizing participation in the agricultural sciences. Specifically, we show how citizen science can reconfigure cost-motivation-accountability combinations using digital tools, open up a larger conceptual space of experimentation, and stimulate new collaborations. With appropriate and persistent institutional support and investment, citizen science can therefore have a lasting impact on how agricultural science engages with farming communities and wider society, and more fully realize the promises of participation

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Micro-Foundations of Organizational Design and Sustainability: The Mediating Role of Learning Ambidexterity

This paper builds on prior scholarly works by examining the relationship between organizing paradox (formalization and decentralization), and organizational levels of learning paradoxes, i.e. exploration and exploitation, and firms’ outcomes (organizational creativity, organizational resilience and organizational energy). Using data from 98 executives and 325 senior employees working across a diverse range of firms operating in the Middle East, the findings suggest that organizing paradox (formalization and decentralization) has a positive impact on learning ambidexterity. In addition, we also found that learning ambidexterity has a positive impact on both organizational resilience and organizational energy. Furthermore, the results indicate that learning ambidexterity mediates the relationship between organizing paradox and organizational creativity. These findings provide important insights into the micro-foundation aspects of organizational ambidexterity