The after-effects of occupational whole-body vibration on human cognitive, visual, and motor function: A systematic review.

Whole-body vibration (WBV) is prevalent in labour-related activities and can have adverse effects on the health and performance of the individuals exposed. However, evidence regarding the extent to which human functionality is affected following occupational WBV exposure has not been collated. The current systematic review sought to synthesize existing literature and assess the strength and direction of evidence regarding the acute after-effects of occupational WBV exposure on cognition, visual function, postural stability, and motor control. We conducted a comprehensive search of AMED, CINAHL, MEDLINE, PubMED, Psychology and Behavioural Sciences Collection, SPORTDiscus, APA PsychInfo, Cochrane Library, EMBASE, HMIC, Global Health, ProQuest Central, Scopus, Web of Science, and the US National Technical Information Service on April 26, 2023. Studies that quantified vibration exposure and measured acute changes in cognition, visual function, postural stability, and motor control from baseline to post-vibration were considered without date restriction. Out of the 2663 studies identified, 32 were eligible for inclusion. Based on the Risk of Bias in Non-Randomized Studies of Exposure (ROBINS-E) tool, the studies demonstrated low (66%), moderate (25%) and high risk of bias (9%). The findings indicate that after exposure to WBV, postural stability either deteriorates or remains unchanged. Inconsistent effects of WBV on cognition were reported, while visual function and motor control showed no pronounced changes following WBV. This might be attributed to assessment limitations such as learning effects in neuropsychological and motor tasks, and non-functional measures of vision employed. There was a lack of consistency in the characterization of vibration exposure and the assessment of associated effects on functional performance. Current evidence is therefore insufficient to provide definitive guidance for updating occupational health and safety regulations regarding WBV. However, this review highlights the potential for WBV to jeopardize post-exposure human performance and, consequently, safety. The completion of the review was supported by a UKRI EPSRC training grant. The review has been registered on PROSPERO (ref CRD42023391075).

The influence of postural threat-induced anxiety on locomotor learning and updating.

The ability to adapt our locomotion in a feedforward (i.e., "predictive") manner is crucial for safe and efficient walking behavior. Equally important is the ability to quickly deadapt and update behavior that is no longer appropriate for the given context. It has been suggested that anxiety induced via postural threat may play a fundamental role in disrupting such deadaptation. We tested this hypothesis, using the "broken escalator" phenomenon: Fifty-six healthy young adults walked onto a stationary walkway ("BEFORE" condition, 5 trials), then onto a moving walkway akin to an airport travelator ("MOVING" condition, 10 trials), and then again onto the stationary walkway ("AFTER" condition, 5 trials). Participants completed all trials while wearing a virtual reality headset, which was used to induce postural threat-related anxiety (raised clifflike drop at the end of the walkway) during different phases of the paradigm. We found that performing the locomotor adaptation phase in a state of increased threat disrupted subsequent deadaptation during AFTER trials: These participants displayed anticipatory muscular activity as if expecting the platform to move and exhibited inappropriate anticipatory forward trunk movement that persisted during multiple AFTER trials. In contrast, postural threat induced during AFTER trials did not affect behavioral or neurophysiological outcomes. These findings highlight that actions learned in the presence of postural threat-induced anxiety are strengthened, leading to difficulties in deadapting these behaviors when no longer appropriate. Given the associations between anxiety and persistent maladaptive gait behaviors (e.g., "overly cautious" gait, functional gait disorders), the findings have implications for the understanding of such conditions.NEW & NOTEWORTHY Safe and efficient locomotion frequently requires movements to be adapted in a feedforward (i.e., "predictive") manner. These adaptations are not always correct, and thus inappropriate behavior must be quickly updated. Here we showed that increased threat disrupts this process. We found that locomotor actions learned in the presence of postural threat-induced anxiety are strengthened, subsequently impairing one's ability to update (or "deadapt") these actions when they are no longer appropriate for the current context.

Can cognitive training capitalise on near transfer effects? Limited evidence of transfer following online inhibition training in a randomised-controlled trial.

Despite early promise, cognitive training research has failed to deliver consistent real-world benefits and questions have been raised about the experimental rigour of many studies. Several meta-analyses have suggested that there is little to no evidence for transfer of training from computerised tasks to real-world skills. More targeted training approaches that aim to optimise performance on specific tasks have, however, shown more promising effects. In particular, the use of inhibition training for improving shoot/don't-shoot decision-making has returned positive far transfer effects. In the present work, we tested whether an online inhibition training task could generate near and mid-transfer effects in the context of response inhibition tasks. As there has been relatively little testing of retention effects in the literature to date, we also examined whether any benefits would persist over a 1-month interval. In a pre-registered, randomised-controlled trial, participants (n = 73) were allocated to either an inhibition training programme (six training sessions of a visual search task with singleton distractor) or a closely matched active control task (that omitted the distractor element). We assessed near transfer to a Flanker task, and mid-transfer to a computerised shoot/don't-shoot task. There was evidence for a near transfer effect, but no evidence for mid-transfer. There was also no evidence that the magnitude of training improvement was related to transfer task performance. This finding adds to the growing body of literature questioning the effectiveness of cognitive training. Given previous positive findings, however, there may still be value in continuing to explore the extent to which cognitive training can capitalise on near or mid-transfer effects for performance optimisation.

The functional role of visual information and fixation stillness in the quiet eye.

The final fixation to a target in far-aiming tasks, known as the quiet eye, has been consistently identified as an important perceptual-cognitive variable for task execution. Yet, despite a number of proposed mechanisms it remains unclear whether the fixation itself is driving performance effects or is simply an emergent property of underpinning cognitions. Across two pre-registered studies, novice golfers (n = 127) completed a series of golf putts in a virtual reality simulation to examine the function of the quiet eye in the absence of visual information. In experiment 1 participants maintained a quiet eye fixation even when all visual information was occluded. Visual occlusion did significantly disrupt motor skill accuracy, but the effect was relatively small (89cm vs 105cm radial error, std. beta = 0.25). In experiment 2, a 'noisy eye' was induced using covertly moving fixation points, which disrupted skill execution (p = .04, BF = 318.07, std. beta = -0.25) even though visual input was equivalent across conditions. Overall, the results showed that performers persist with a long pre-shot fixation even in the absence of visual information, and that the stillness of this fixation confers a functional benefit that is not merely related to improved information extraction.

Exome Sequencing and the Identification of New Genes and Shared Mechanisms in Polymicrogyria.

Importance: Polymicrogyria is the most commonly diagnosed cortical malformation and is associated with neurodevelopmental sequelae including epilepsy, motor abnormalities, and cognitive deficits. Polymicrogyria frequently co-occurs with other brain malformations or as part of syndromic diseases. Past studies of polymicrogyria have defined heterogeneous genetic and nongenetic causes but have explained only a small fraction of cases. Objective: To survey germline genetic causes of polymicrogyria in a large cohort and to consider novel polymicrogyria gene associations. Design, Setting, and Participants: This genetic association study analyzed panel sequencing and exome sequencing of accrued DNA samples from a retrospective cohort of families with members with polymicrogyria. Samples were accrued over more than 20 years (1994 to 2020), and sequencing occurred in 2 stages: panel sequencing (June 2015 to January 2016) and whole-exome sequencing (September 2019 to March 2020). Individuals seen at multiple clinical sites for neurological complaints found to have polymicrogyria on neuroimaging, then referred to the research team by evaluating clinicians, were included in the study. Targeted next-generation sequencing and/or exome sequencing were performed on probands (and available parents and siblings) from 284 families with individuals who had isolated polymicrogyria or polymicrogyria as part of a clinical syndrome and no genetic diagnosis at time of referral from clinic, with sequencing from 275 families passing quality control. Main Outcomes and Measures: The number of families in whom genetic sequencing yielded a molecular diagnosis that explained the polymicrogyria in the family. Secondarily, the relative frequency of different genetic causes of polymicrogyria and whether specific genetic causes were associated with co-occurring head size changes were also analyzed. Results: In 32.7% (90 of 275) of polymicrogyria-affected families, genetic variants were identified that provided satisfactory molecular explanations. Known genes most frequently implicated by polymicrogyria-associated variants in this cohort were PIK3R2, TUBB2B, COL4A1, and SCN3A. Six candidate novel polymicrogyria genes were identified or confirmed: de novo missense variants in PANX1, QRICH1, and SCN2A and compound heterozygous variants in TMEM161B, KIF26A, and MAN2C1, each with consistent genotype-phenotype relationships in multiple families. Conclusions and Relevance: This study's findings reveal a higher than previously recognized rate of identifiable genetic causes, specifically of channelopathies, in individuals with polymicrogyria and support the utility of exome sequencing for families affected with polymicrogyria.

Sengers syndrome and AGK-related disorders - Minireview of phenotypic variability and clinical outcomes in molecularly confirmed cases.

Sengers syndrome (OMIM# 212350) is a rare autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the AGK gene, which encodes the acylglycerol kinase enzyme. The syndrome was originally defined as a "triad" of hypertrophic cardiomyopathy, cataracts, and lactic acidosis, with or without skeletal myopathy. The clinical manifestation of Sengers Syndrome exhibits substantial heterogeneity, with mild and severe/infantile forms reported. Further, biallelic AGK pathogenic variants have also been identified in a familial case of non-syndromic isolated cataract (OMIM# 614691), expanding our understanding of the gene's influence beyond the originally defined syndrome. In this study, we provide a systematic review of molecularly confirmed cases with biallelic AGK pathogenic variants (Supplementary Table 1). Our analysis demonstrates the variable expressivity and penetrance of the central features of Sengers syndrome, as follows: cataracts (98%), cardiomyopathy (88%), lactic acidosis (adjusted 88%), and skeletal myopathy (adjusted 74%) (Table 1). Furthermore, we investigate the associations between genotype, biochemical profiles, and clinical outcomes, with a particular focus on infantile mortality. Our findings reveal that patients carrying homozygous nonsense variants have a higher incidence of infant mortality and a lower median age of death (p = 0.005 and p = 0.02, Table 2a). However, the location of pathogenic variants within the AGK domains was not significantly associated with infantile death (p = 0.62, Table 2b). Additionally, we observe a borderline association between the absence of lactic acidosis and longer survival (p = 0.053, Table 2c). Overall, our systematic review sheds light on the diverse clinical manifestations of AGK-related disorders and highlights potential factors that influence its prognosis. These provide important implications for the diagnosis, treatment, and counseling of affected individuals and families.

A systematic literature review of evidence for the use of assistive exoskeletons in defence and security use cases.

Advances in assistive exoskeleton technology, and a boom in related scientific literature, prompted a need to review the potential use of exoskeletons in defence and security. A systematic review examined the evidence for successful augmentation of human performance in activities deemed most relevant to military tasks. Categories of activities were determined a priori through literature scoping and Human Factors workshops with military stakeholders. Workshops identified promising opportunities and risks for integration of exoskeletons into military use cases. The review revealed promising evidence for exoskeletons' capacity to assist with load carriage, manual lifting, and working with tools. However, the review also revealed significant gaps in exoskeleton capabilities and likely performance levels required in the use case scenarios. Consequently, it was recommended that a future roadmap for introducing exoskeletons to military environments requires development of performance criteria for exoskeletons that can be used to implement a human-centred approach to research and development.

We assessed the state-of-the-art for the use of wearable assistive exoskeletons in UK defence and security use cases. A full systematic review of the literature was undertaken, informed by use cases developed in military stakeholder workshops. Clear gaps in exoskeleton capability and use case requirements were identified, leading to recommendations for future work.

A Bayesian computational model to investigate expert anticipation of a seemingly unpredictable ball bounce.

During dynamic and time-constrained sporting tasks performers rely on both online perceptual information and prior contextual knowledge to make effective anticipatory judgments. It has been suggested that performers may integrate these sources of information in an approximately Bayesian fashion, by weighting available information sources according to their expected precision. In the present work, we extended Bayesian brain approaches to anticipation by using formal computational models to estimate how performers weighted different information sources when anticipating the bounce direction of a rugby ball. Both recreational (novice) and professional (expert) rugby players (n = 58) were asked to predict the bounce height of an oncoming rugby ball in a temporal occlusion paradigm. A computational model, based on a partially observable Markov decision process, was fitted to observed responses to estimate participants' weighting of online sensory cues and prior beliefs about ball bounce height. The results showed that experts were more sensitive to online sensory information, but that neither experts nor novices relied heavily on prior beliefs about ball trajectories in this task. Experts, but not novices, were observed to down-weight priors in their anticipatory decisions as later and more precise visual cues emerged, as predicted by Bayesian and active inference accounts of perception.

Treatment and Prevention of Cardiovascular Implantable Electronic Device (CIED) Infections.

An expanded role for cardiac implantable electronic devices (CIEDs) in recent decades reflects an aging population and broader indications for devices, including both primary prevention and management of dysrhythmias. CIED infection is one of the most important device-related complications and has a major impact on mortality, quality of life, healthcare utilization, and cost. Unfortunately, the investigation and management of CIED infection remain complex, often necessitating complete and timely removal of the device and leads in order to eradicate the infection. In addition, the translation of knowledge from an extensive literature to a disparate group of medical practitioners has often been inadequate. This review of CIED infection management highlights the significant advances made during the past decade, including diagnostic criteria, advanced imaging, and next-generation sequencing for culture-negative cases or those in which uncertainty remains. We also outline the role and indication for powered lead extraction, the process of antibiotic choice and treatment duration, considerations related to the timing and location for reimplantation, and preimplantation risk stratification and associated interventions to reduce the risk of CIED infection.

L'élargissement du rôle des dispositifs électroniques cardiaques implantables (DECI) au cours des dernières décennies reflète le vieillissement de la population et les indications plus vastes des dispositifs, notamment dans la prévention primaire et la prise en charge des dysrythmies. Les infections liées aux DECI sont l'une des plus importantes complications liées aux dispositifs et ont des conséquences majeures sur la mortalité, la qualité de vie, l'utilisation et les coûts des soins de santé. Malheureusement, le dépistage et la prise en charge des infections liées aux DECI demeurent complexes et nécessitent souvent le retrait complet et rapide du dispositif et des sondes en vue d'éradiquer l'infection. De plus, l'application des connaissances issues d'une vaste littérature à un groupe disparate de médecins praticiens a souvent été inadéquate. La présente revue sur la prise en charge des infections liées aux DECI illustre les avancées importantes réalisées au cours de la dernière décennie, notamment les critères diagnostiques, l'imagerie avancée et le séquençage de prochaine génération des cas à culture négative ou de ceux pour lesquels des incertitudes demeurent. Nous avons aussi décrit le rôle et les indications d'extraction des sondes fonctionnelles, le processus du choix des antibiotiques et de la durée du traitement, les considérations relatives au moment et au lieu de la réimplantation, et la stratification du risque en préimplantation et les interventions associées afin de réduire le risque d'infections liées aux DECI.

An Active Inference Account of Skilled Anticipation in Sport: Using Computational Models to Formalise Theory and Generate New Hypotheses.

Optimal performance in time-constrained and dynamically changing environments depends on making reliable predictions about future outcomes. In sporting tasks, performers have been found to employ multiple information sources to maximise the accuracy of their predictions, but questions remain about how different information sources are weighted and integrated to guide anticipation. In this paper, we outline how predictive processing approaches, and active inference in particular, provide a unifying account of perception and action that explains many of the prominent findings in the sports anticipation literature. Active inference proposes that perception and action are underpinned by the organism's need to remain within certain stable states. To this end, decision making approximates Bayesian inference and actions are used to minimise future prediction errors during brain-body-environment interactions. Using a series of Bayesian neurocomputational models based on a partially observable Markov process, we demonstrate that key findings from the literature can be recreated from the first principles of active inference. In doing so, we formulate a number of novel and empirically falsifiable hypotheses about human anticipation capabilities that could guide future investigations in the field.

A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay.

We report seven affected individuals from six families with a recurrent, de novo variant in the ARPC4 gene (c.472C>T [p.Arg158Cys (GenBank: NM_005718.4)]). Core features in affected individuals include microcephaly, mild motor delays, and significant speech impairment. ARPC4 is a core subunit of the actin-related protein (ARP2/3) complex, which catalyzes the formation of F-actin networks. We show that the recurrent ARPC4 missense change is associated with a decreased amount of F-actin in cells from two affected individuals. Taken together, our results implicate heterozygous ARPC4 missense variants as a cause of neurodevelopmental disorders and microcephaly.

Transcranial direct current stimulation and sporting performance: A systematic review and meta-analysis of transcranial direct current stimulation effects on physical endurance, muscular strength and visuomotor skills.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been linked with a range of physiological and cognitive enhancements relevant to sporting performance. As a number of positive and null findings have been reported in the literature, the present meta-analysis sought to synthesise results across endurance, strength and visuomotor skill domains to investigate if tDCS improves any aspect of sporting performance. Online database searches in August 2020 identified 43 full-text studies which examined the acute effects of tDCS compared to sham/control conditions on physical endurance, muscular strength, and visuomotor skills in healthy adults. Meta-analysis indicated a small overall effect favouring tDCS stimulation over sham/control (standardized mean difference (SMD) = 0.25, CI95%[.14;.36]). Effects on strength (SMD = 0.31, CI95%[.10;.51]) and visuomotor (SMD = 0.29, CI95%[.00;.57]) tasks were larger than endurance performance (SMD = 0.18, CI95%[.00;.37]). Meta-regressions indicated effect sizes were not related to stimulation parameters, but other factors such as genetics, gender, and experience may modulate tDCS effects. The results suggest tDCS has the potential to be used as an ergogenic aid in conjunction with a specified training regime.

Assessment of cognitive biases in Augmented Reality: Beyond eye tracking.

We study an individual's propensity for rational thinking; the avoidance of cognitive biases (unconscious errors generated by our mental simplification methods) using a novel augmented reality (AR) platform. Specifically, we developed an odd-one-out (OOO) game-like task in AR designed to try to induce and assess confirmatory biases. Forty students completed the AR task in the laboratory, and the short form of the comprehensive assessment of rational thinking (CART) online via the Qualtrics platform. We demonstrate that behavioural markers (based on eye, hand and head movements) can be associated (linear regression) with the short CART score - more rational thinkers have slower head and hand movements and faster gaze movements in the second more ambiguous round of the OOO task. Furthermore, short CART scores can be associated with the change in behaviour between two rounds of the OOO task (one less and one more ambiguous) - hand-eye-head coordination patterns of the more rational thinkers are more consistent in the two rounds. Overall, we demonstrate the benefits of augmenting eye-tracking recordings with additional data modalities when trying to understand complicated behaviours.

Predictive eye movements are adjusted in a Bayes-optimal fashion in response to unexpectedly changing environmental probabilities.

This study examined the application of active inference to dynamic visuomotor control. Active inference proposes that actions are dynamically planned according to uncertainty about sensory information, prior expectations, and the environment, with motor adjustments serving to minimise future prediction errors. We investigated whether predictive gaze behaviours are indeed adjusted in this Bayes-optimal fashion during a virtual racquetball task. In this task, participants intercepted bouncing balls with varying levels of elasticity, under conditions of higher or lower environmental volatility. Participants' gaze patterns differed between stable and volatile conditions in a manner consistent with generative models of Bayes-optimal behaviour. Partially observable Markov models also revealed an increased rate of associative learning in response to unpredictable shifts in environmental probabilities, although there was no overall effect of volatility on this parameter. Findings extend active inference frameworks into complex and unconstrained visuomotor tasks and present important implications for a neurocomputational understanding of the visual guidance of action.

Resistance of African tropical forests to an extreme climate anomaly.

The responses of tropical forests to environmental change are critical uncertainties in predicting the future impacts of climate change. The positive phase of the 2015-2016 El Niño Southern Oscillation resulted in unprecedented heat and low precipitation in the tropics with substantial impacts on the global carbon cycle. The role of African tropical forests is uncertain as their responses to short-term drought and temperature anomalies have yet to be determined using on-the-ground measurements. African tropical forests may be particularly sensitive because they exist in relatively dry conditions compared with Amazonian or Asian forests, or they may be more resistant because of an abundance of drought-adapted species. Here, we report responses of structurally intact old-growth lowland tropical forests inventoried within the African Tropical Rainforest Observatory Network (AfriTRON). We use 100 long-term inventory plots from six countries each measured at least twice prior to and once following the 2015-2016 El Niño event. These plots experienced the highest temperatures and driest conditions on record. The record temperature did not significantly reduce carbon gains from tree growth or significantly increase carbon losses from tree mortality, but the record drought did significantly decrease net carbon uptake. Overall, the long-term biomass increase of these forests was reduced due to the El Niño event, but these plots remained a live biomass carbon sink (0.51 ± 0.40 Mg C ha-1 y-1) despite extreme environmental conditions. Our analyses, while limited to African tropical forests, suggest they may be more resistant to climatic extremes than Amazonian and Asian forests.

Visuo-motor attention during object interaction in children with developmental coordination disorder.

Developmental coordination disorder (DCD) describes a condition of poor motor performance in the absence of intellectual impairment. Despite being one of the most prevalent developmental disorders, little is known about how fundamental visuomotor processes might function in this group. One prevalent idea is children with DCD interact with their environment in a less predictive fashion than typically developing children. A metric of prediction which has not been examined in this group is the degree to which the hands and eyes are coordinated when performing manual tasks. To this end, we examined hand and eye movements during an object lifting task in a group of children with DCD (n = 19) and an age-matched group of children without DCD (n = 39). We observed no differences between the groups in terms of how well they coordinated their hands and eyes when lifting objects, nor in terms of the degree by which the eye led the hand. We thus find no evidence to support the proposition that children with DCD coordinate their hands and eyes in a non-predictive fashion. In a follow-up exploratory analysis we did, however, note differences in fundamental patterns of eye movements between the groups, with children in the DCD group showing some evidence of atypical visual sampling strategies and gaze anchoring behaviours during the task.

Tectonics, climate and the diversification of the tropical African terrestrial flora and fauna.

Tropical Africa is home to an astonishing biodiversity occurring in a variety of ecosystems. Past climatic change and geological events have impacted the evolution and diversification of this biodiversity. During the last two decades, around 90 dated molecular phylogenies of different clades across animals and plants have been published leading to an increased understanding of the diversification and speciation processes generating tropical African biodiversity. In parallel, extended geological and palaeoclimatic records together with detailed numerical simulations have refined our understanding of past geological and climatic changes in Africa. To date, these important advances have not been reviewed within a common framework. Here, we critically review and synthesize African climate, tectonics and terrestrial biodiversity evolution throughout the Cenozoic to the mid-Pleistocene, drawing on recent advances in Earth and life sciences. We first review six major geo-climatic periods defining tropical African biodiversity diversification by synthesizing 89 dated molecular phylogeny studies. Two major geo-climatic factors impacting the diversification of the sub-Saharan biota are highlighted. First, Africa underwent numerous climatic fluctuations at ancient and more recent timescales, with tectonic, greenhouse gas, and orbital forcing stimulating diversification. Second, increased aridification since the Late Eocene led to important extinction events, but also provided unique diversification opportunities shaping the current tropical African biodiversity landscape. We then review diversification studies of tropical terrestrial animal and plant clades and discuss three major models of speciation: (i) geographic speciation via vicariance (allopatry); (ii) ecological speciation impacted by climate and geological changes, and (iii) genomic speciation via genome duplication. Geographic speciation has been the most widely documented to date and is a common speciation model across tropical Africa. We conclude with four important challenges faced by tropical African biodiversity research: (i) to increase knowledge by gathering basic and fundamental biodiversity information; (ii) to improve modelling of African geophysical evolution throughout the Cenozoic via better constraints and downscaling approaches; (iii) to increase the precision of phylogenetic reconstruction and molecular dating of tropical African clades by using next generation sequencing approaches together with better fossil calibrations; (iv) finally, as done here, to integrate data better from Earth and life sciences by focusing on the interdisciplinary study of the evolution of tropical African biodiversity in a wider geodiversity context.

A critical analysis of the functional parameters of the quiet eye using immersive virtual reality.

Directing ocular fixations toward a target assists the planning and control of visually guided actions. In far aiming tasks, the quiet eye, an instance of premovement gaze anchoring, has been extensively studied as a key performance variable. However, theories of quiet eye are yet to establish the exact functional role of the location and duration of the fixation. The present work used immersive virtual reality to manipulate key parameters of the quiet eye-location (Experiment 1) and duration (Experiment 2)-to test competing theoretical predictions about their importance. Across two preregistered experiments, novice participants (n = 127) completed a series of golf putts while their eye movements, putting accuracy, and putting kinematics were recorded. In Experiment 1, participants' premovement fixation was cued to locations on the ball, near the ball, and far from the ball. In Experiment 2, long and short quiet eye durations were induced using auditory tones as cues to movement phases. Linear mixed effects models indicated that manipulations of location and duration had little effect on performance or movement kinematics. The findings suggest that, for novices, the spatial and temporal parameters of the final fixation may not be critical for movement preprogramming and may instead reflect attentional control or movement inhibition functions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Molecular screening indicates high prevalence and mixed infections of Hepatozoon parasites in wild felines from South Africa.

Genetic diversity within partial 18S rRNA sequences from Hepatozoon protozoan parasites from wild felines in South Africa was assessed and compared with data from domestic cats to assess patterns of host specificity. Lions, leopards, servals, a caracal and an African wildcat were all positive for parasites of the Hepatozoon felis-complex. However, haplotypes were not species-specific, and potential mixed infections were widespread. Additional genetic markers are needed to untangle the extremely complex situation of these parasites in both domestic cats and wild felines in South Africa.

De novo variants in MPP5 cause global developmental delay and behavioral changes.

Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein essential for cell polarity, fate and survival. Defects in cell polarity are associated with neurologic disorders including autism and microcephaly. MPP5 is essential for neurogenesis in animal models, but human variants leading to neurologic impairment have not been described. We identified three patients with heterozygous MPP5 de novo variants (DNV) and global developmental delay (GDD) and compared their phenotypes and magnetic resonance imaging (MRI) to ascertain how MPP5 DNV leads to GDD. All three patients with MPP5 DNV experienced GDD with language delay/regression and behavioral changes. MRI ranged from normal to decreased gyral folding and microcephaly. The effects of MPP5 depletion on the developing brain were assessed by creating a heterozygous conditional knock out (het CKO) murine model with central nervous system (CNS)-specific Nestin-Cre drivers. In the het CKO model, Mpp5 depletion led to microcephaly, decreased cerebellar volume and cortical thickness. Het CKO mice had decreased ependymal cells and Mpp5 at the apical surface of cortical ventricular zone compared with wild type. Het CKO mice also failed to maintain progenitor pools essential for neurogenesis. The proportion of cortical cells undergoing apoptotic cell death increased, suggesting that cell death reduces progenitor population and neuron number. Het CKO mice also showed behavioral changes, similar to our patients. To our knowledge, this is the first report to show that variants in MPP5 are associated with GDD, behavioral abnormalities and language regression/delay. Murine modeling shows that neurogenesis is likely altered in these individuals, with cell death and skewed cellular composition playing significant roles.