Learning to Walk With Deep Reinforcement Learning: Forward Dynamic Simulation of a Physics-Based Musculoskeletal Model of an Osseointegrated Transfemoral Amputee.

This paper leverages the OpenSim physics-based simulation environment for the forward dynamic simulation of an osseointegrated transfemoral amputee musculoskeletal model, wearing a generic prosthesis. A deep reinforcement learning architecture, which combines the proximal policy optimization algorithm with imitation learning, is designed to enable the model to walk by using three different observation states. The first is a complete state that includes the agent's kinematics, ground reaction forces, and muscle data; the second is a reduced state that only includes the kinematics and ground reaction forces; the third is an augmented state that combines the kinematics and ground reaction forces with a prediction of the muscle data generated by a fully-connected feed-forward neural network. The empirical results demonstrate that the model trained with the augmented observation state can achieve walking patterns with rewards and gait symmetry ratings comparable to those of the model trained with the complete observation state, while there are no symmetric walking patterns when using the reduced observation state. This paper shows the importance of including muscle data in a deep reinforcement learning architecture for the forward dynamic simulation of musculoskeletal models of transfemoral amputees.

The community engagement course and action network: strengthening community and academic research partnerships to advance health equity.

Background: Historically Black Colleges and Universities and Minority Serving Institutions are uniquely positioned to implement community-campus research partnerships based on a history of service, the pursuit of community trustworthiness and student demographics often similar to surrounding marginalized communities. The Morehouse School of Medicine Prevention Research Center collaborates with members of Historically Black Colleges and Universities, Minority Serving Institutes, and community organizations on the Community Engaged Course and Action Network. This network is the first of its kind and aims to strengthen members' ability to implement Community-Based Participatory Research (CBPR) principles and partnerships. Projects address public health priorities including mental health among communities of color, zoonotic disease prevention, and urban food deserts. Materials and methods: To assess the effectiveness of the network, a Participatory Evaluation framework was implemented to conduct process evaluation which included review of partnership structures, operations, project implementation processes, and preliminary outcomes of the research collaborations. A focus group of Community Engagement Course and Action Network members (community and academic) was also conducted to identify benefits and challenges of the network with emphasis on key areas for improvement to further enhance the relationships between partners and to facilitate their subsequent community-campus research. Results: Network improvements were tied to themes strengthening community-academic partnerships including sharing and fellowship, coalition building and collaboration, and greater connections and awareness of community needs through their current community-academic partnerships. The need to conduct ongoing evaluation during and after implementation, for determining the early adoption of CBPR approaches was also identified. Conclusion: Evaluation of the network's processes, infrastructure, and operation provides early lessons learned to strengthen the network. Ongoing assessment is also essential for ensuring continuous quality improvement across partnerships such as determining CBPR fidelity, assessing partnership synergy, and dynamics, and for quality improvement of research protocol. The implications and potential for advancing implementation science through this and similar networks are great towards advancing leadership in modeling how foundations in community service can advance to CBPR partnership formation and ultimately, health equity approaches, that are local defined and assessed.

Impact of the Covid pandemic on health care equity in NHS General Dental Practice.

INTRODUCTION: Oral health inequalities existed before Covid, but the pandemic presented an unprecedented challenge for health services. Our aim was to determine whether patient groups at risk of health care inequality due to the pandemic could be identified from NHS dental claims. METHODS: Secondary analysis of routinely collected NHS Business Services Authority data for patients treated by General Dental Practitioners in England and Wales between April 2019 and January 2022 to assess the effect of the Covid pandemic on claims for patients attending general dental practices. Data for treatment items claimed after the start of the first lockdown were compared to the pre-lockdown period. RESULTS: The proportion of claims for child fillings, child extractions and child fluoride varnish application after March 2020 were lower than equivalent proportions for adults, in both England and Wales. Similarly, there were consistently fewer claims for fillings and extractions for patients claiming pension credit guarantee credit than all pensioners in both England and Wales. CONCLUSION: The Covid pandemic may have caused health care inequality for children and patients claiming pension credit guarantee credit. This may compound the inequality in oral health for these patients.

If you rise, I fall: Equality is prevented by the misperception that it harms advantaged groups.

Nine preregistered studies (n = 4197) demonstrate that advantaged group members misperceive equality as necessarily harming their access to resources and inequality as necessarily benefitting them. Only when equality is increased within their ingroup, instead of between groups, do advantaged group members accurately perceive it as unharmful. Misperceptions persist when equality-enhancing policies offer broad benefits to society or when resources, and resource access, are unlimited. A longitudinal survey of the 2020 U.S. voters reveals that harm perceptions predict voting against actual equality-enhancing policies, more so than voters' political and egalitarian beliefs. Finally two novel-groups experiments experiments reveal that advantaged participants' harm misperceptions predict voting for inequality-enhancing policies that financially hurt them and against equality-enhancing policies that financially benefit them. Misperceptions persist even after an intervention to improve decision-making. This misperception that equality is necessarily zero-sum may explain why inequality prevails even as it incurs societal costs that harm everyone.

Detecting Prejudice From Egalitarianism: Why Black Americans Don't Trust White Egalitarians' Claims.

Although White Americans increasingly express egalitarian views, how they express egalitarianism may reveal inegalitarian tendencies and sow mistrust with Black Americans. In the present experiments, Black perceivers inferred likability and trustworthiness and accurately inferred underlying racial attitudes and motivations from White writers' declarations that they are nonprejudiced and egalitarian (Experiments 1 and 2). White writers believed that their egalitarianism seemed more inoffensive and indicative of allyship than was perceived by Black Americans (Experiment 1a). Linguistic analysis revealed that, when inferring racial attitudes and motivations, Black perceivers accurately attended to language emphasizing humanization, support for equal opportunity, personal responsibility, and the idea that equality already exists (Experiment 1b). We found causal evidence that these linguistic cues informed Black Americans' perceptions of White egalitarians (Experiment 2). Suggesting societal costs of these perceptions, White egalitarians' underlying racial beliefs negatively predicted Black participants' actual trust and cooperation in an economic game (Experiment 3). Our experiments (N = 1,335 adults) showed that White Americans' insistence that they are egalitarian itself perpetuates mistrust with Black Americans.

The molecular basis of spinocerebellar ataxia type 48 caused by a de novo mutation in the ubiquitin ligase CHIP.

The spinocerebellar ataxias (SCAs) are a class of incurable diseases characterized by degeneration of the cerebellum that results in movement disorder. Recently, a new heritable form of SCA, spinocerebellar ataxia type 48 (SCA48), was attributed to dominant mutations in STIP1 homology and U box-containing 1 (STUB1); however, little is known about how these mutations cause SCA48. STUB1 encodes for the protein C terminus of Hsc70 interacting protein (CHIP), an E3 ubiquitin ligase. CHIP is known to regulate proteostasis by recruiting chaperones via a N-terminal tetratricopeptide repeat domain and recruiting E2 ubiquitin-conjugating enzymes via a C-terminal U-box domain. These interactions allow CHIP to mediate the ubiquitination of chaperone-bound, misfolded proteins to promote their degradation via the proteasome. Here we have identified a novel, de novo mutation in STUB1 in a patient with SCA48 encoding for an A52G point mutation in the tetratricopeptide repeat domain of CHIP. Utilizing an array of biophysical, biochemical, and cellular assays, we demonstrate that the CHIPA52G point mutant retains E3-ligase activity but has decreased affinity for chaperones. We further show that this mutant decreases cellular fitness in response to certain cellular stressors and induces neurodegeneration in a transgenic Caenorhabditis elegans model of SCA48. Together, our data identify the A52G mutant as a cause of SCA48 and provide molecular insight into how mutations in STUB1 cause SCA48.

Majority members misperceive even "win-win" diversity policies as unbeneficial to them.

Six studies show that majority members misperceive diversity policies as unbeneficial to their ingroup, even when policies benefit them. Majority members perceived nonzero-sum university admission policies-policies that increase acceptance of both URM (i.e., underrepresented minority) and non-URM applicants-as harmful to their ingroup when merely framed as "diversity" policies. Even for policies lacking a diversity framing (i.e., "leadership" policies), majority members misperceived that their ingroup would not benefit when policies provided relatively greater benefit to URMs, but not when they provided relatively greater benefit to non-URMs. No consistent evidence emerged that these effects were driven by ideological factors: Majority members' misperceptions occurred even when accounting for self-reported beliefs around diversity, hierarchy, race, and politics. Instead, we find that majority group membership itself predicts misperceptions, such that both Black and White participants accurately perceive nonzero-sum diversity policies as also benefiting the majority when participants are represented as members of the minority group. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The impact of signposting and group support pathways on a community-based physical activity intervention grounded in motivational interviewing.

BACKGROUND: Brief advice is recommended to increase physical activity (PA) within primary care. This study assessed change in PA levels and mental well-being after a motivational interviewing (MI) community-based PA intervention and the impact of signposting (SP) and social action (SA) (i.e. weekly group support) pathways. METHODS: Participants (n = 2084) took part in a community-based, primary care PA programme using MI techniques. Self-reported PA and mental well-being data were collected at baseline (following an initial 30-min MI appointment), 12 weeks, 6 months and 12 months. Participants were assigned based upon the surgery they attended to the SP or SA pathway. Multilevel models derived point estimates and 95% confidence intervals for outcomes at each time point and change scores. RESULTS: Participants increased PA and mental well-being at each follow-up time point through both participant pathways and with little difference between pathways. Retention was similar between pathways at 12 weeks, but the SP pathway retained more participants at 6 and 12 months. CONCLUSIONS: Both pathways produced similar improvements in PA and mental well-being; however, the addition of a control would have provided further insight as to the effectiveness. Due to lower resources yet similar effects, the SP pathway could be incorporated to support PA in primary care settings.

Findings in 1,123 Men with Preoperative 68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography and Multiparametric Magnetic Resonance Imaging Compared to Totally Embedded Radical Prostatectomy Histopathology: Implications for the Diagnosis and Management of Prostate Cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT) is recommended for staging of prostate cancer, but its additional benefit above mpMRI alone in local evaluation for prostate cancer is unclear. The study aim was to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination, to predict tumor location and Gleason score ≥3+4 on robot-assisted laparoscopic radical prostatectomy (RALP) histology. MATERIALS AND METHODS: We retrospectively reviewed 1,123 men with a preoperative mpMRI and 68Ga-PSMA PET/CT prior to a RALP. Tumor locations were collected from both imaging modalities and compared to totally embedded prostate histology. Lowest apparent diffusion coefficient value on mpMRI and the highest maximum standardized uptake value (SUVmax) on 68Ga-PSMA PET/CT were collected on the index lesions to perform analysis on detection rates. RESULTS: Median prostate specific antigen was 6. Median Gleason score on biopsy and RALP histology was 4+3. The index lesion and multifocal tumor detection were similar between mpMRI and 68Ga-PSMA PET/CT (p=0.10; p=0.11). When combining mpMRI and 68Ga-PSMA PET/CT, index Gleason score ≥3+4 cancer at RALP was identified in 92%. Only 10% of patients with Gleason score ≤3+4 on biopsy with an SUVmax <5 were upgraded to ≥4+3 on RALP histology, compared to 90% if the SUVmax was >11. CONCLUSIONS: The addition of a diagnostic 68Ga-PSMA PET/CT to mpMRI can improve the detection of significant prostate cancer and improve the ability to identify men suitable for active surveillance.

Demand for regional level III neonatal services is not reduced during national COVID lockdowns.

Following the first peak of the COVID-19 pandemic, reports from around the world suggested a reduction in preterm deliveries during lockdown periods. We reviewed preterm admissions to a large tertiary neonatal unit in inner North East London during two United Kingdom (UK) national lockdowns in 2020 and 2021. We found no evidence of difference in admissions during two national lockdowns compared to previous years. Based on these findings, we recommend that neonatal services remain as vigilant and prepared as ever for the unpredictable nature of preterm birth, and their staff protected to provide this highly specialist care.

Empirical audit and review and an assessment of evidentiary value in research on the psychological consequences of scarcity.

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.

A new species of Proegernia from the Namba Formation in South Australia and the early evolution and environment of Australian egerniine skinks.

The diverse living Australian lizard fauna contrasts greatly with their limited Oligo-Miocene fossil record. New Oligo-Miocene fossil vertebrates from the Namba Formation (south of Lake Frome, South Australia) were uncovered from multiple expeditions from 2007 to 2018. Abundant disarticulated material of small vertebrates was concentrated in shallow lenses along the palaeolake edges, now exposed on the western of Lake Pinpa also known from Billeroo Creek 2 km northeast. The fossiliferous lens within the Namba Formation hosting the abundant aquatic (such as fish, platypus Obdurodon and waterfowl) and diverse terrestrial (such as possums, dasyuromorphs and scincids) vertebrates and is hereafter recognized as the Fish Lens. The stratigraphic provenance of these deposits in relation to prior finds in the area is also established. A new egerniine scincid taxon Proegernia mikebulli sp. nov. described herein, is based on a near-complete reconstructed mandible, maxilla, premaxilla and pterygoid. Postcranial scincid elements were also recovered with this material, but could not yet be confidently associated with P. mikebulli. This new taxon is recovered as the sister species to P. palankarinnensis, in a tip-dated total-evidence phylogenetic analysis, where both are recovered as stem Australian egerniines. These taxa also help pinpoint the timing of the arrival of scincids to Australia, with egerniines the first radiation to reach the continent.

Relationships between nitrogen cycling microbial community abundance and composition reveal the indirect effect of soil pH on oak decline.

Tree decline is a global concern and the primary cause is often unknown. Complex interactions between fluctuations in nitrogen (N) and acidifying compounds have been proposed as factors causing nutrient imbalances and decreasing stress tolerance of oak trees. Microorganisms are crucial in regulating soil N available to plants, yet little is known about the relationships between soil N-cycling and tree health. Here, we combined high-throughput sequencing and qPCR analysis of key nitrification and denitrification genes with soil chemical analyses to characterise ammonia-oxidising bacteria (AOB), archaea (AOA) and denitrifying communities in soils associated with symptomatic (declining) and asymptomatic (apparently healthy) oak trees (Quercus robur and Q. petraea) in the United Kingdom. Asymptomatic trees were associated with a higher abundance of AOB that is driven positively by soil pH. No relationship was found between AOA abundance and tree health. However, AOA abundance was driven by lower concentrations of NH4+, further supporting the idea of AOA favouring lower soil NH4+ concentrations. Denitrifier abundance was influenced primarily by soil C:N ratio, and correlations with AOB regardless of tree health. These findings indicate that amelioration of soil acidification by balancing C:N may affect AOB abundance driving N transformations, reducing stress on declining oak trees.

British Journal of Biomedical Science in 2020. What have we learned?

Each year the British Journal of Biomedical Science publishes a 'What have we learned' editorial designed to introduce readers within the major disciplines of laboratory medicine to developments outside their immediate area. In addition it is designed to inform a wider readership of the advances in the diagnosis and treatment of disease. To this end, in 2020 the journal published 39 articles covering the disciplines within Biomedical Science in the 4 issues comprising volume 77. These included a review of COVID-19 in this issue, 27 original articles, 6 Biomedical Science 'In Brief' and 4 case histories. 27 of the articles involved molecular techniques, with one of these comparing results with a mass spectrometry based method. The preponderance of molecular genetic studies gives us a good idea of the likely future direction of the disciplines.

Testing of a (Spiritual) Self-Assessment Tool ((S)SAT) in a Community Hospital Setting.

The (Spiritual) Self-Assessment Tool Study was designed to test the novel engagement tool's effectiveness. Providing the (Spiritual) Self-Assessment Tool Study to newly admitted medical patients led to few instances where the tool was completed. Nevertheless, the (Spiritual) Self-Assessment Tool Study patient questionnaire generated significant secondary findings: a third of responding patients consider their hospital care incomplete without their care team having access to (Spiritual) Self-Assessment Tool data. Nursing staff also desire this data, but are unable to access it without the (Spiritual) Self-Assessment Tool or an equivalent source.

RHDV2 epidemic in UK pet rabbits. Part 2: PCR results and correlation with vaccination status.

OBJECTIVE: To report PCR results and vaccination status of rabbits with rabbit haemorrhagic disease following an investigation into sudden or unexpected death. MATERIALS AND METHODS: PCR testing for RHDV2 and RHDV1 was performed on rabbit liver samples at two laboratories. Laboratory A reported results as positive or negative; Laboratory B reported results quantitatively as RNA copies per mg liver, categorised as negative, inconclusive or positive. The vaccination status of rabbits with both histopathological features of rabbit haemorrhagic disease and positive PCR test results were collated. RESULTS: PCR results matched histopathological findings in 188 of 195 (96%) cases. Seven individuals showed equivocal results, all of which had histopathological features of RHD but three tested PCR-negative and four results conflicted between laboratories. RHDV2 was the serotype detected in all PCR-positive cases. Histological features of rabbit haemorrhagic disease and PCR test results were positive in 125 rabbits; 51 unvaccinated, 56 in-date with Nobivac Myxo-RHD and 13 vaccinated against RHDV2 - although nine of these were vaccinated within 10 days of death. CLINICAL SIGNIFICANCE: PCR testing complements histopathology in cases of sudden death in rabbits by confirming the diagnosis and identifying virus serotype, but there can be false negatives. Although RHDV2 is currently prevalent in UK pet rabbits, vaccination against both RHDV1 and RHDV2 is recommended. Failures of RHDV2 vaccine are infrequent.

RHDV2 epidemic in UK pet rabbits. Part 1: clinical features, gross post mortem and histopathological findings.

OBJECTIVES: To report clinical features, gross post mortem and histopathological findings from an investigation into sudden or unexpected death in rabbits that was undertaken during an outbreak of rabbit haemorrhagic disease. MATERIALS AND METHODS: Using a standard protocol, veterinarians were invited to submit case histories and results of their post mortem examination of pet rabbits that died unexpectedly. Histopathological examination of heart, lungs, liver, spleen and kidney samples was collated with macroscopic appearance and clinical details. RESULTS: Hepatocellular necrosis, characteristic of rabbit haemorrhagic disease, was observed in 185 of 300 (62%) submissions, often accompanied by glomerular thrombosis and changes in other organs. Evidence of rabbit haemorrhagic disease was not apparent on histopathology in 113 of 300 (38%) rabbits. Gross post mortem examination by veterinary practitioners did not always reflect reported histopathological changes. No macroscopic abnormalities were seen in 78/185 (42%) of rabbit haemorrhagic disease cases. Rapid death and death of other rabbits in the household were common features of rabbit haemorrhagic disease. Ante mortem clinical signs included anorexia, collapse, lethargy, seizures, icterus, bleeding from the mouth, dyspnoea, hypothermia, pyrexia, bradycardia or poor blood clotting. CLINICAL IMPORTANCE: Rabbit haemorrhagic disease can be suspected from a history of sudden death, especially if multiple rabbits are affected. There is not always macroscopic evidence of the disease but histopathology is useful to support or refute a diagnosis of rabbit haemorrhagic disease and provide information about other causes of death.