The influence of cognitive resources on compensatory arm responses

The purpose of this study was to determine the influence of an ongoing cognitive task on an individual’s ability to generate a compensatory arm response. Twenty young and 16 older adults recovered their balance from a support surface translation while completing a cognitive (counting) task of varying difficulty. Surface electromyographic (EMG) recordings from the shoulders and kinematics of the right arm were collected to quantify the compensatory arm response. Results indicated that the counting task, regardless of its difficulty as well as the age of the individual, had minimal influence on the onset or magnitude of arm muscle activity that occurred following a loss of balance. In contrast to previous research, this study’s findings suggest that the cortical or cognitive resources utilized by the cognitive task are not relied upon for the generation of compensatory arm responses and that older adults are not disproportionately affected by dual-tasking than young adults

The cellular and synaptic architecture of the mechanosensory dorsal horn

The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception

Using sociotechnical theory to understand medication safety work in primary care and prescribers’ use of clinical decision support:a qualitative study

Objectives: The concept of safety work draws attention to the intentional work of ensuring safety within care systems. Clinical decision support (CDS) has been designed to enhance medication safety in primary care by providing decision-making support to prescribers. Sociotechnical theory understands that healthcare settings are complex and dynamically connected systems of fluid networks, human agents, changing relationships and social processes. This study aimed to understand the relationship between safety work and the use of CDS. Design and setting: This qualitative study took place across nine different general practices in England. Stakeholders included general practitioners (GPs) and general practice-based pharmacists and nurse prescribers. Semi-structured interviews were conducted to illicit how the system was used by the participants in the context of medication safety work. Data analysis conducted alongside data collection was thematic and drew on socio-technical theory. Participants: Twenty-three interviews were conducted with 14 GPs, three nurse prescribers and three practice pharmacists between February 2018 and June 2020. Results: Safety work was contextually situated in a complex network of relationships. Three interconnected themes were interpreted from the data: (1) the use of CDS within organisational and social practices and workflows; (2) safety work and the use of CDS within the interplay between prescribers, patients and populations; and (3) the affordances embedded in CDS systems. Conclusion: The use of sociotechnical theory here extends current thinking in patient safety particularly in the ways that safety work was co-constituted with the use of CDS alerts. This has implications for implementation and use to ensure that the contexts into which such CDS systems are implemented are taken into account. Understanding how alerts can adapt safety culture will help improve the efficacy of CDS systems, enhance prescribing safety and help to further understand how safety work is achieved in primary care

High Throughput Automated Analysis of Big Flow Cytometry Data

The rapid expansion of flow cytometry applications has outpaced the functionality of traditional manual analysis tools used to interpret flow cytometry data. Scientists are faced with the daunting prospect of manually identifying interesting cell populations in 50-dimensional datasets, equalling the complexity previously only reached in mass cytometry. Data can no longer be analyzed or interpreted fully by manual approaches. While automated gating has been the focus of intense efforts, there are many significant additional steps to the analytical pipeline (e.g., cleaning the raw files, event outlier detection, extracting immunophenotypes). We review the components of a customized automated analysis pipeline that can be generally applied to large scale flow cytometry data. We demonstrate these methodologies on data collected by the International Mouse Phenotyping Consortium (IMPC)

The Impact of Moderate Altitude on Manifestations of Coronary Artery Disease

Background: Reductions in oxygen availability at altitude reduce oxygen supply to the myocardium. This reduction in oxygen supply may be problematic for patients with cardiovascular disease and/or associated comorbidities such as hypertension, diabetes, or heart failure. Summary: The risk of adverse cardiovascular events may be increased at altitude as a result of the interaction between hypoxia and exercise, which further increases myocardial demand for oxygen. When an acute coronary syndrome occurs, outcomes may be suboptimal given limited access to medical centers with cardiac catheterization laboratories and sudden cardiac death may occur. Pretravel planning should prioritize optimizing cardiovascular health and mitigating associated risk factors to reduce risk. Key Messages: Patients should have a realistic expectation of the types of activities that can be undertaken at altitude based on their underlying cardiovascular risk profile. Travel itineraries should include a period of acclimatization to hypoxia before initiating planned activities. In this review, we provide an overview of the relevant physiology related to hypoxia, its impact on cardiovascular function and clinical considerations and management strategies for patients and providers to reduce risk of adverse events from occurring in austere environments

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

Strategies supporting sustainable prescribing safety improvement interventions in English primary care: A qualitative study

Background: While the use of prescribing safety indicators (PSI) can reduce potentially hazardous prescribing, there is a need to identify actionable strategies for the successful implementation and sustainable delivery of PSI-based interventions in general practice.Aim: To identify strategies for the successful implementation and sustainable use of PSI-based interventions in routine primary care.Design & setting: Qualitative study in primary care settings across England.Method: Anchoring on a complex pharmacist-led IT-based intervention (PINCER) and clinical decision support (CDS) for prescribing and medicines management, a qualitative study was conducted using sequential, multiple methods. The methods comprised documentary analysis, semi-structured interviews, and online workshops to identify challenges and possible solutions to the longer-term sustainability of PINCER and CDS. Thematic analysis was used for the documentary analysis and stakeholder workshops, while template analysis was used for the semi-structured interviews. Findings across the three methods were synthesised using the RE-AIM (reach, efficacy, adoption, implementation, and maintenance) framework.Results: Forty-eight documents were analysed, and 27 interviews and two workshops involving 20 participants were undertaken. Five main issues were identified, which aligned with the adoption and maintenance dimensions of RE-AIM: fitting into current context (adoption); engaging hearts and minds (maintenance); building resilience (maintenance); achieving engagement with secondary care (maintenance); and emphasising complementarity (maintenance).Conclusion: Extending ownership of prescribing safety beyond primary care-based pharmacists, and achieving greater alignment between general practice and hospital prescribing safety initiatives, is fundamental to achieve sustained impact of PSI-based interventions in primary care