Motor skill competence and moderate- and vigorous-intensity physical activity: a linear and non-linear cross-sectional analysis of eight pooled trials.

BACKGROUND: Few studies have examined the relationship between motor skill competence and device-measured physical activity in large samples and none have used non-linear modelling. This study assessed the linear and non-linear associations between motor skill competence and physical activity in children using pooled data from eight studies. METHODS: Cross-sectional ActiGraph accelerometer and motor skills competence data from 988 children (50.8% boys) aged 3-11 years were included. Total, object control and locomotor skill competence were assessed using the Test of Gross Motor Skill Development. Linear mixed models were fitted to examine linear associations between motor skill competence and physical activity. Then, restricted cubic splines models were used to assess potential non-linear relationships. Interactions by sex and age were assessed. RESULTS: There was evidence of positive linear associations between total skill, and object control and locomotor skills, with moderate- and vigorous-intensity physical activity; however, the associations with total skill competence and object control better fitted a non-linear model. Non-linear models indicated associations were positive but relatively weak in the low to mid ranges of TGMD/object control scores but at high ranges (~ > 70 out of 100/ and ~ 35 out of 50) the association strength increased for both moderate- and vigorous-intensity physical activity. There were sex interactions for locomotor skills only, specifically for vigorous activity with boys having a stronger positive association than girls. CONCLUSIONS: There appears to be a threshold for object control skill proficiency that children need to reach to enhance their physical activity levels which provides support for a motor skill "proficiency barrier". This provides a tangible benchmark for children to achieve in motor competence programs.

True grit? Comparative anatomy and evolution of gizzards in fishes.

Gut morphology frequently reflects the food organisms digest. Gizzards are organs of the gut found in archosaurs and fishes that mechanically reduce food to aid digestion. Gizzards are thought to compensate for edentulism and/or provide an advantage when consuming small, tough food items (e.g., phytoplankton and algae). It is unknown how widespread gizzards are in fishes and how similar these structures are among different lineages. Here, we investigate the distribution of gizzards across bony fishes to (1) survey different fishes for gizzard presence, (2) compare the histological structure of gizzards in three species, (3) estimate how often gizzards have evolved in fishes, and (4) explore whether anatomical and ecological traits like edentulism and microphagy predict gizzard presence. According to our analyses, gizzards are rare across bony fishes, evolving only six times in a broad taxonomic sampling of 51 species, and gizzard presence is not clearly correlated with factors like gut length or dentition. We find that gizzard morphology varies among the lineages where one is present, both macroscopically (presence of a crop) and microscopically (varying tissue types). We conclude that gizzards likely aid in the mechanical reduction of food in fishes that have lost an oral dentition in their evolutionary past; however, the relative scarcity of gizzards suggests they are just one of many possible solutions for processing tough, nutrient-poor food items. Gizzards have long been present in the evolutionary history of fishes, can be found in a wide variety of marine and freshwater clades, and likely have been overlooked in many taxa.

Signal of harm in morphine use in adults with acute pulmonary oedema: A rapid systematic review.

BACKGROUND: Heart failure affects nearly 65 million people globally, resulting in recurrent hospital admissions and substantial healthcare expenditure. The use of morphine in the management of acute pulmonary oedema remains controversial, with conflicting guidance and significant variation in practice. Synthesised evidence is needed to inform standard treatment guidelines and clinical practice. OBJECTIVE: To determine whether morphine should be used in the treatment of acute pulmonary oedema (APE) in adults. METHODS: A rapid review of systematic reviews of randomised controlled trials or observational studies, and then randomised controlled trials, was conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and one clinical trial registry on 12 February 2022. We used a prespecified protocol following Cochrane rapid review methods and aligned to the National Standard Treatment Guidelines and Essential Medicines List methodology. We first considered relevant high-quality systematic reviews of randomised controlled trials or observational studies, then (if required) randomised controlled trials to inform time-sensitive or urgent evidence requests, clinical practice, policy, or standard treatment guidelines. RESULTS: We identified four systematic reviews of observational studies. The two most relevant, up-to-date, and highest-quality reviews were used to inform evidence for critical outcomes. Morphine may increase in-hospital mortality (odds ratio (OR) 1.78; 95% confidence interval (CI) 1.01 - 3.13; low certainty of evidence; six observational studies, n=151 735 participants), resulting in 15 more per 1 000 hospital deaths, ranging from 0 to 40 more hospital deaths. Morphine may result in a large increase in invasive mechanical ventilation (OR 2.72; 95% CI 1.09 - 6.80; low certainty of evidence; four observational studies, n=167 847 participants), resulting in 45 more per 1 000 ventilations, ranging from 2 more to 136 more. Adverse events and hospital length of stay were not measured across reviews or trials. CONCLUSION: Based on the most recent, relevant and best-available quality evidence, morphine use in adults with APE may increase in-hospital and all-cause mortality and may result in a large increase in the need for invasive mechanical ventilation compared to not using morphine. Recommending against the use of morphine in pulmonary oedema may improve patient outcomes. Disinvesting in morphine for this indication may result in cost savings, noting the possible accrued benefits of fewer patients requiring invasive ventilation and management of morphine-related side-effects.

Randomized evaluation of an online single-session intervention for minority stress in LGBTQ+ adolescents.

Background: LGBTQ+ youth face myriad adverse health outcomes due to minority stress, creating a need for accessible, mechanism-targeted interventions to mitigate these minority stress-related risk factors. We tested the effectiveness and acceptability of Project RISE, an online single-session intervention designed to ameliorate internalized stigma and improve other outcomes among LGBTQ+ youth. We hypothesized that youth assigned to RISE (versus a control) would report significantly reduced internalized stigma and increased identity pride at post-intervention and at two-week follow-up and would find RISE acceptable. Methods: We recruited adolescents nationally through Instagram advertisements in May 2022 (N = 538; M age = 15.06, SD age = 0.97). Participants were randomly assigned to RISE or an information-only control and completed questionnaires pre-intervention, immediately post-intervention, and two weeks post-intervention. Inclusion criteria included endorsing: (1) LGBTQ+ identity, (2) age 13-16, (3) English fluency (4) Internet access, and (5) subjective negative impact of LGBTQ+ stigma. Results: Relative to participants in the control condition, participants who completed RISE reported significant decreases in internalized stigma (d = -0.49) and increases in identity pride (d = 0.25) from pre- to immediately post-intervention, along with decreased internalized stigma (d = -0.26) from baseline to two-week follow-up. Participants rated both RISE and the information-only control as highly, equivalently acceptable. Conclusions: RISE appears to be an acceptable and useful online SSI for LGBTQ+ adolescents, with potential to reduce internalized stigma in both the short- and longer-term. Future directions include evaluating effects of Project RISE over longer follow-ups and in conjunction with other mental health supports.

Meta-analytic magic, ivermectin, and socially responsible reporting.

Some clinicians prescribe ivermectin for COVID-19 despite a lack of support from any credible South African professional body. They argue that when faced by clinical urgency, weak signals of efficacy should trigger action if harm is unlikely. Several recent reviews found an apparent mortality benefit by including studies at high risk of bias and with active rather than placebo controls. If these studies are discounted, the pooled mortality effect is no longer statistically significant, and evidence of benefit is very weak. Relying on this evidence could cause clinical harm if used to justify vaccine hesitancy. Clinicians remain responsible for ensuring that guidance they follow is both legitimate and reliable. In the ivermectin debate, evidence-based medicine (EBM) principles have largely been ignored under the guise thatin a pandemic the 'rules are different', probably to the detriment of vulnerable patients and certainly to the detriment of the profession's image. Medical schools and professional interest groups are responsible for transforming EBM from a taught but seldom-used tool into a process of lifelong learning, promoting a consistent call for evidence-based and unconflicted debate integral to clinical practice.

The moment of tooth: rate, fate and pattern of Pacific lingcod dentition revealed by pulse-chase.

Tooth replacement rates of polyphyodont cartilaginous and bony fishes are hard to determine because of a lack of obvious patterning and maintaining specimens long enough to observe replacement. Pulse-chase is a fluorescent technique that differentially colours developing mineralized tissue. We present in situ tooth replacement rate and position data for the oral and pharyngeal detentions of Ophiodon elongatus (Pacific lingcod). We assessed over 10 000 teeth, in 20 fish, and found a daily replacement rate of about two teeth (3.6% of the dentition). The average tooth is in the dental battery for 27 days. The replacement was higher in the lower pharyngeal jaw (LPJ). We found no difference between replacement rates of feeding and non-feeding fish, suggesting feeding was not a driver of tooth replacement. Lingcod teeth have both a size and location fate; smaller teeth at one spot will not grow into larger teeth, even if a large tooth nearby is lost. We also found increased rates of replacement at the posterior of the LPJ relative to the anterior. We propose that lingcod teeth do not migrate in the jaw as they develop; their teeth are fated in size and location, erupting in their functional position.

Adverse drug reactions reported to a provincial public health sector pharmacovigilance programme in South Africa.

BACKGROUND: There are limited data in South Africa (SA) on adverse drug reaction (ADR) patterns and common causative medicines, outside of HIV and tuberculosis treatment programmes. In SA, Western Cape Province has a pharmacovigilance programme that collects spontaneous reports of suspected ADRs from public sector healthcare facilities. OBJECTIVES: To describe reports received by the pharmacovigilance programme over a 4-year period (excluding those ascribed to medicines used to treat HIV and tuberculosis), as well as challenges faced in the implementation of such a system. METHODS: Reports of suspected ADRs and deaths possibly related to ADRs received between January 2015 and December 2018 were reviewed. Causality was assessed by a pharmacist, with multidisciplinary team involvement for all deaths and complicated cases. Causality was categorised according to the World Health Organization-Uppsala Monitoring Centre system. Preventability was assessed using Schumock and Thornton criteria. Observations on preventability and challenges faced in the operation of a spontaneous reporting system were also noted. RESULTS: We received 5 346 reports containing 6 023 suspected ADRs. There were 5 486 ADRs confirmed after causality assessment, in 5 103 reports. Cough, angio-oedema, movement disorders and uterine bleeding disorders were the most common ADRs. Enalapril, etonogestrel, amlodipine and hydrochlorothiazide were the most commonly implicated drugs. Seven deaths were reported; 3 of these reports of deaths had confirmed ADRs, and these ADRs were assessed as contributing to the deaths. Approximately 3.8% of commonly reported ADRs were preventable. CONCLUSIONS: Enalapril and etonogestrel were responsible for a significant proportion of ADRs reported to this provincial programme. Future work should include quantification of preventability aspects to better inform gaps in healthcare worker knowledge that can be addressed in order to improve patient care.

Essential medicine selection during the COVID-19 pandemic: Enabling access in uncharted territory.

The COVID-19 pandemic requires urgent decisions regarding treatment policy in the face of rapidly evolving evidence. In response, the South African Essential Medicines List Committee established a subcommittee to systematically review and appraise emerging evidence, within very short timelines, in order to inform the National Department of Health COVID-19 treatment guidelines. To date, the subcommittee has reviewed 14 potential treatments, and made recommendations based on local context, feasibility, resource requirements and equity. Here we describe the rapid review and evidence-to-decision process, using remdesivir and dexamethasone as examples. Our experience is that conducting rapid reviews is a practical and efficient way to address medicine policy questions under pandemic conditions.

P-Hacking Lexical Richness Through Definitions of "Type" and "Token".

"P-hacking" is the repeated analysis of data until a statistically significant result is achieved. We show that p-hacking can also occur during data generation, sometimes unintentionally. We use the type-token ratio to demonstrate that differences in the definitions of "type" and "token" can produce significantly different results. Since these terms are rarely defined in the biomedical literature, the result is an inability to meaningfully interpret the body of literature that makes use of this measure.

The Role of Developmental Integration and Historical Contingency in the Origin and Evolution of Cypriniform Trophic Novelties.

While functional morphologists have long studied the evolution of anatomical structures, the origin of morphological novelties has received less attention. When such novelties first originate they must become incorporated into an integrated system to be rendered fully functional. Thus, developmental integration is key at the origin of morphological novelties. However, given enough evolutionary time such integration may be broken, allowing for a division of labor that is facilitated by subsequent decoupling of structures. Cypriniformes represent a diverse group of freshwater fishes characterized by several trophic novelties that include: kinethmoid-mediated premaxillary protrusion, a muscular palatal and post-lingual organ, hypertrophied lower pharyngeal jaws that masticate against the base of the neurocranium, novel pharyngeal musculature controlling movement of the hypertrophied lower pharyngeal jaws, and in a few species an incredibly complex epibranchial organ used to aggregate filtered phytoplankton. Here, we use the wealth of such trophic novelties in different cypriniform fishes to present case studies in which developmental integration allowed for the origin of morphological innovations. As proposed in case studies 1 and 2 trophic innovations may be associated with both morphological and lineage diversification. Alternatively, case studies 3 and 4 represent a situation where ecological niche was expanded but with no concomitant increase in species diversity.

Open Agile text mining for bioinformatics: the PubAnnotation ecosystem.

MOTIVATION: Most currently available text mining tools share two characteristics that make them less than optimal for use by biomedical researchers: they require extensive specialist skills in natural language processing and they were built on the assumption that they should optimize global performance metrics on representative datasets. This is a problem because most end-users are not natural language processing specialists and because biomedical researchers often care less about global metrics like F-measure or representative datasets than they do about more granular metrics such as precision and recall on their own specialized datasets. Thus, there are fundamental mismatches between the assumptions of much text mining work and the preferences of potential end-users. RESULTS: This article introduces the concept of Agile text mining, and presents the PubAnnotation ecosystem as an example implementation. The system approaches the problems from two perspectives: it allows the reformulation of text mining by biomedical researchers from the task of assembling a complete system to the task of retrieving warehoused annotations, and it makes it possible to do very targeted customization of the pre-existing system to address specific end-user requirements. Two use cases are presented: assisted curation of the GlycoEpitope database, and assessing coverage in the literature of pre-eclampsia-associated genes. AVAILABILITY AND IMPLEMENTATION: The three tools that make up the ecosystem, PubAnnotation, PubDictionaries and TextAE are publicly available as web services, and also as open source projects. The dictionaries and the annotation datasets associated with the use cases are all publicly available through PubDictionaries and PubAnnotation, respectively.

The effects of synthetic cannabinoids (SCs) on brain structure and function.

There is an increasing use of "Novel Psychoactive Substances" containing synthetic cannabinoids worldwide. Synthetic cannabinoids (SC) are highly addictive and cause severe adverse effects. The purpose of our study was to assess whether chronic use of SC alters brain volume and function. Fifteen SC chronic users and 15 healthy control participants undertook an MRI scan to assess brain volume and function while performing a working memory N-back task and a response-inhibition Go-No-Go task. SC users showed impaired performance on the N-back task but not on the Go-No-Go task. They also showed reduced total gray matter volume compared with control participants, as well as reduced gray matter volume in several cortical regions including the middle frontal gyrus, frontal orbital gyrus, inferior frontal gyrus, insula, anterior cingulate cortex and the precuneus. Moreover, SC users showed diminished brain activations in the precuneus, cuneus, lingual gyrus, hippocampus and cerebellum while performing the N-back task. No differences were found in brain activation while performing the response-inhibition task. This is the first study showing overall reduced grey matter volume and specific reduced grey matter volumes in chronic SC users. Furthermore, this study showed for the first time impairment in the neural brain mechanisms responsible for working memory in SC users. Our results of reduced grey matter density and diminished activation during a working memory task in SC users, may suggest vulnerability of the frontal-parietal network in chronic SC users.

Poor anticoagulation control in patients taking warfarin at a tertiary and district-level prothrombin clinic in Cape Town, South Africa.

BACKGROUND: Warfarin is the most commonly used anticoagulant for both primary and secondary prevention of thromboembolism. For anticoagulation efficacy, the international normalised ratio (INR) needs to be within the therapeutic range for at least 65% of time on warfarin. OBJECTIVES: To describe INR control in patients on long-term warfarin and identified predictors of good INR control at two dedicated warfarin follow-up clinics in Cape Town, South Africa (SA). METHODS: We reviewed clinical records of patients in care at the INR clinics at Mitchell's Plain Community Health Centre and Groote Schuur Hospital. We included patients who had been on warfarin therapy for at least 27 months and excluded patients with <6 months of INR monitoring data or a >70-day gap between INR tests in the calculation period, and if >25% of follow-up time was at an alternative site. The time in therapeutic range (TTR) over 180 days using the Rosendaal method was calculated, and we categorised INR control as good if the TTR was ≥65%. We constructed a multivariate logistic regression model to identify associations with good INR control. RESULTS: We included 363 patients, with a median age of 55 years (interquartile range (IQR) 44 - 64), of whom 65.6% were women. The most common indications for warfarin were valvular heart disease (45.7%) and atrial fibrillation (25.1%). The mean TTR was 47%, with only 91/363 patients having good INR control. In a multivariate model adjusted for age, sex, clinic and target INR, patients aged ≥55 years were more likely to have good INR control than younger patients (adjusted odds ratio 1.69, 95% confidence interval 1.03 - 2.79). Poorly controlled patients had more frequent INR monitoring than those with good INR control, with a median of 8 INRs (IQR 6 - 10) v. 6 INRs (IQR 5 - 8) in the 180-day period (p<0.0001). CONCLUSIONS: Only 25.1% of patients in our study achieved good INR control, despite regular INR monitoring. There is an urgent need to improve anticoagulation control of patients receiving warfarin in SA. Validated dosing algorithms are required, and access to lower warfarin dosage formulations may optimise individual dose titration. Advocacy for these formulations is advised.

Describing key performance indicators for waiting times in emergency centres in the Western Cape Province, South Africa, between 2013 and 2014.

BACKGROUND: Data measured as key performance indicators (KPIs) are used internationally in emergency medicine to measure and monitor quality of care. The Department of Health in the Western Cape Province, South Africa, introduced time-based KPIs for emergency centres (ECs) in 2012. OBJECTIVES: To describe the most recently processed results of the audits conducted in Western Cape ECs between 2013 and 2014. METHODS: A retrospective, descriptive study was conducted on data collected in the 6-monthly Western Cape EC triage and waiting time audits for 2013 - 2014. Time variables were analysed overall and per triage category. ECs in hospitals were compared with ECs in community health centres (CHCs). A descriptive analysis of the sample was undertaken. Proportions for categorical data are presented throughout. The continuous variable time was described using means and standard deviations. The χ2 test and Fisher's exact test were used to describe associations. The level of significance was p<0.05, with the 95% confidence interval where appropriate. RESULTS: There was no significant difference in triage acuity proportions between hospital and CHC ECs. Waiting times were longer than recommended for the South African Triage Scale, but higher-acuity patients were seen faster than lower-acuity patients. Waiting times were significantly longer at hospitals than at CHCs. A red priority patient presenting to a CHC would take 6.1 times longer to reach definitive care than if the patient had presented to a hospital EC. CONCLUSIONS: The triage process appears to improve waiting times for the sickest patients, although it is protracted throughout. Acutely ill patient journeys starting at CHC ECs suggested significant delays in care. Models need to be explored that allow appropriate care at the first point of contact and rapid transfer if needed. To improve waiting times, resource allocation in the emergency care system will need to be reconsidered.

Optical skyrmion lattice in evanescent electromagnetic fields.

Topological defects play a key role in a variety of physical systems, ranging from high-energy to solid-state physics. A skyrmion is a type of topological defect that has shown promise for applications in the fields of magnetic storage and spintronics. We show that optical skyrmion lattices can be generated using evanescent electromagnetic fields and demonstrate this using surface plasmon polaritons, imaged by phase-resolved near-field optical microscopy. We show how the optical skyrmion lattice exhibits robustness to imperfections while the topological domain walls in the lattice can be continuously tuned, changing the spatial structure of the skyrmions from bubble type to Néel type. Extending the generation of skyrmions to photonic systems provides various possibilities for applications in optical information processing, transfer, and storage.

Three Dimensions of Reproducibility in Natural Language Processing.

Despite considerable recent attention to problems with reproducibility of scientific research, there is a striking lack of agreement about the definition of the term. That is a problem, because the lack of a consensus definition makes it difficult to compare studies of reproducibility, and thus to have even a broad overview of the state of the issue in natural language processing. This paper proposes an ontology of reproducibility in that field. Its goal is to enhance both future research and communication about the topic, and retrospective meta-analyses. We show that three dimensions of reproducibility, corresponding to three kinds of claims in natural language processing papers, can account for a variety of types of research reports. These dimensions are reproducibility of a conclusion, of a finding, and of a value. Three biomedical natural language processing papers by the authors of this paper are analyzed with respect to these dimensions.

A Modular Ontology for Modeling Service Provision in a Communication Network for Coordination of Care.

This paper presents a modular ontology of health care in the context in Amyotrophic Lateral Sclerosis. 4 modules cover socio-environmental, medical, and care coordination aspects of the domain. They are organized by a core module. Its goal is to understand interruptions in health care provision in the context of a neurodegenerative disease.

Fitness variation among host species and the paradox of ineffective rhizobia.

Legumes can preferentially select beneficial rhizobial symbionts and sanction ineffective strains that fail to fix nitrogen. Yet paradoxically, rhizobial populations vary from highly beneficial to ineffective in natural and agricultural soils. Classic models of symbiosis focus on the single dimension of symbiont cost-benefit to sympatric hosts, but fail to explain the widespread persistence of ineffective rhizobia. Here, we test a novel framework predicting that spatio-temporal and community dynamics can maintain ineffective strains in rhizobial populations. We used clonal and multistrain inoculations and quantitative culturing to investigate the relative fitness of four focal Bradyrhizobium strains varying from effective to ineffective on Acmispon strigosus. We found that an ineffective Bradyrhizobium strain can be sanctioned by its native A. strigosus host across the host's range, forming fewer and smaller nodules compared to beneficial strains. But the same ineffective Bradyrhizobium strain exhibits a nearly opposite pattern on the broadly sympatric host Acmispon wrangelianus, forming large nodules in both clonal and multistrain inoculations. These data suggest that community-level effects could favour the persistence of ineffective rhizobia and contribute to variation in symbiotic nitrogen fixation.

Improving precision in concept normalization.

Most natural language processing applications exhibit a trade-off between precision and recall. In some use cases for natural language processing, there are reasons to prefer to tilt that trade-off toward high precision. Relying on the Zipfian distribution of false positive results, we describe a strategy for increasing precision, using a variety of both pre-processing and post-processing methods. They draw on both knowledge-based and frequentist approaches to modeling language. Based on an existing high-performance biomedical concept recognition pipeline and a previously published manually annotated corpus, we apply this hybrid rationalist/empiricist strategy to concept normalization for eight different ontologies. Which approaches did and did not improve precision varied widely between the ontologies.