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Abstract Background In an ageing population, low impact fragility fractures are becoming increasingly common. However, fracture risk can be reduced where low bone density can be identified at an early stage. In this study we aim to demonstrate that IBEX Bone Health (IBEX BH) can provide a clinically useful prediction from wrist radiographs of aBMD and T-score at the ultra-distal (UD) and distal-third (DT) regions of the radius. Methods A 261-participant single-centre, non-randomised, prospective, study was carried out to compare a) IBEX BH, a quantitative digital radiography software device, to b) Dual-energy X-ray Absorptiometry (DXA). A total of 257 participants with wrist digital radiograph (DR), forearm DXA pairs were included in the analysis after exclusions. Results The adjusted R2 value for IBEX BH outputs to the radial areal bone mineral density (aBMD) produced by a GE Lunar DXA system for the UD region is 0.87 (99% Confidence Interval (CI) [0.84, 0.89]). The adjusted R2 value for IBEX BH outputs to aBMD for the DT region is 0.88 (99% CI [0.85, 0.90]). The Area Under the Receiver Operating Characteristic curve (AUC) for the forearm T-score ≤ − 2.5 risk prediction model at the UD region is 0.95 (99% CI [0.93, 0.98]). The AUC for the forearm T-score ≤ − 2.5 risk prediction model at the DT region is 0.98 (99% CI [0.97, 0.99]). Conclusion From a DR of the wrist, IBEX BH provides a clinically useful i) estimate of aBMD at the two regions of interest on the radius and ii) risk prediction model of forearm T-score ≤ − 2.5 at the UD and DT regions.

Abstract Transcutaneous vagus nerve stimulation (tVNS) is a promising technique for enhancing cognitive performance and skill acquisition. Yet, its efficacy for enhancing learning rate and long-term retention in an ecologically valid learning environment has not been demonstrated. We conducted two double-blind sham-controlled experiments examining the efficacy of auricular tVNS (taVNS: Experiment (1) and cervical tVNS (tcVNS: Experiment (2), on a 5 day second-language vocabulary acquisition protocol among highly selected career linguists at the US Department of Defense’s premier language school. tcVNS produced accelerated recall performance during training (Day 2–4), benefits of which were maintained across a 24 h retention interval with no stimulation at the final test. Consistent with prior work, tcVNS also produced fatigue-mitigating and focus-promoting effects as measured by the Air Force Research Laboratory Mood Questionnaire. Based on the current and the previous findings supporting tVNS’ efficacy on performance, training enhancement, and fatigue mitigation, we believe tcVNS to be an effective learning acceleration tool that can be utilized at language-teaching and other institutions focused on intensive training of cognitive skills.

Abstract Formal theoretical models propose that cooperative networks can be maintained when individuals condition behavior on social standing. Here, we empirically examine the predictions of such models of positive and negative indirect reciprocity using a suite of network-structured economic games in four rural Colombian communities (N i n d = 496 individuals, N o b s = 53,876 ratings/transfers). We observe that, at a dyadic-level, individuals have a strong tendency to exploit and punish others in bad standing (e.g., those perceived as selfish), and allocate resources to those in good standing (e.g., those perceived as generous). These dyadic findings scale to a more generalized, community level, where reputations for being generous are associated with receipt of allocations, and reputations for being selfish are associated with receipt of punishment. These empirical results illustrate the roles that both positive and negative reciprocity, and costly punishment, play in sustaining community-wide cooperation networks.

Bioblitzes are a tool for the rapid appraisal of biodiversity and are particularly useful in remote and understudied regions and for understudied taxa. Lichens are an example of an often overlooked group, despite being widespread in virtually all terrestrial ecosystems and having many important ecological functions.We report the lichens and allied fungi collected during the 2018 terrestrial bioblitz conducted on Calvert Island on the Central Coast of British Columbia, Canada. We identified 449 specimens belonging to 189 species in 85 genera, increasing the total number of species known from Calvert Island to 194, and generated Internal Transcribed Spacer (ITS) sequences for 215 specimens from 121 species. Bryoria furcellata, Chaenothecopsis lecanactidis and C. nigripunctata were collected for the first time in British Columbia. We also found Pseudocyphellaria rainierensis, which is listed as Special Concern on the federal Species at Risk Act, and other rarely reported species in British Columbia including Opegrapha sphaerophoricola, Protomicarea limosa, Raesaenenia huuskonenii and Sarea difformis. We demonstrate that DNA barcoding improves the scope and accuracy of expert-led bioblitzes by facilitating the detection of cryptic species and allowing for consistent identification of chemically and morphologically overlapping taxa. Despite the spatial and temporal limitations of our study, the results highlight the value of intact forest ecosystems on the Central Coast of British Columbia for lichen biodiversity, education and conservation.

Risk index tools have the potential to assist farmers in making strategic decisions regarding their farm design to manage losses of nutrients. Such tools require a vulnerability framework, and these are often based on scores or rankings. These frameworks struggle to take account of interactions between elements of the physical environment. Process-based simulation models inherently take account of interactions and may be a viable alternative to score-based methods. We describe the method to populate a database of transport factors that covers the agricultural lands of New Zealand that is designed for usage as the susceptibility framework within a risk index tool. The method gives both leaching and runoff transport factors and gives values by month. The simulation model used had already been validated for simulating water and nitrogen balances and the generated spatial patterns of the transport factors was validated via expert assessment. These features allow good representation of the risks posed across a wide range of farming activities. • Use of a simulation model to quantify transport factors. • Captures the interactions between soil and weather factors in the physical environment. • Produces a country-wide database intended as a susceptibility framework for a risk index tool.

AbstractPerforming head CT in intoxicated patients presenting to the emergency department (ED) is common, yet low yield. In our previous study, acute findings were found only in patients with at least one of: neurological Deficits, Intubation, Trauma, Convulsions or Headache. We hypothesise that the absence of these DITCH clinical features rules out the need for immediate CT. We collected data for intoxicated patients attending EDs in our district from March 2021 to May 2022 inclusive. We recorded clinical presentation features, agents, disposition and head CT results. There were 1,308 intoxicated patients out of a total of 219,273 ED presentations. Median age was 38 years. Common ingestions were ethanol, stimulants, GABA-ergics and opioids. 407 patients (31%) had head CT, with 31 patients (7.6%) having 36 acute findings: 19 intracranial haemorrhages, 8 fractures, 2 cerebral oedema and 7 haematomas. All patients with acute CT findings had one of the DITCH features, and all had trauma. The sensitivity and NPV of the hypothesis were 100%. In patients that were not scanned, there were no re-presentations.Our internal validation study is further evidence that acute findings on head CT in intoxicated patients presenting to the ED are only found in those who had one of the DITCH features.

Background: Distal radius fractures are a common presentation in the orthopedic practice. There is extensive literature on the appropriate management of these injuries based on age, displacement, and other factors. Attritional tendon ruptures are a rare but described complication in both surgically and closed managed fractures. We report a case of delayed extensor indicis and extensor digitorum tendon rupture after conservatively managed distal radius fracture. Case report: A 68 year old female presents with a right wrist injury after a mechanical fall. She was found to have an isolated right distal radius fracture with minimal displacement. She was immobilized in a splint for 5 weeks and progressed to full weightbearing activity at 8 weeks. 14 weeks after injury, she suffered attritional rupture of the EIP and EDC tendons to the index finger. Intraoperatively impending rupture of the EPL tendon was also noted. She successfully underwent tendon reconstruction but had persistent index extensor lag at final follow-up. Literature review: There are 643,000 distal radius fractures annually, with an extensor tendon rupture incidence of up to 5% in those treated without surgery. This most commonly involves the EPL tendon. Tendon reconstruction and tendon transfer are the mainstays of operative management of these complications. Clinical relevance: Distal radius fractures with attritional tendon ruptures present a relatively rare but challenging problem. This case reports one of the only examples of isolated index extensor rupture in an adult and highlights the importance of clinical vigilance and patient counseling on the possible complications.

This paper demonstrates how Longitudinal Qualitative Research (LQR) is an innovative method to understand the lived experiences of members of minoritized groups when temporality is a structuring element of their experiences. Most qualitative research in psychology is cross-sectional, which limits our understanding of individuals whose experiences are context-dependent and linked to the temporal norms of specific social environments. LQR is unique for allowing researchers to compare change and stability over time and reveal how social challenges and barriers impact perspective shifts and long-term decision-making. To demonstrate the usefulness of LQR as an inclusive methodology, we discuss an ongoing study of career decision-making among a diverse cohort of biomedical scientists. We have used annual interviews to follow biomedical science trainees from the beginning of their PhD into the initial stages of their careers. We present case studies of minoritized scientists to illustrate the methods for long-term engagement used to elicit sensitive and critical information during their training. We show how LQR is a viable methodology for a variety of research questions and can be accomplished using large or small sample sizes and limited resources. Our primary goal is to show how LQR is useful to understand the experiences of minoritized individuals in contexts that have historically excluded them.

BackgroundOlder people can experience health and social challenges such as loneliness, depression, and lack of social connectedness. There is need for programs and approaches that address the growing incidence of social isolation and loneliness for older people. One initiative that aims to address these challenges is the Sporting Memories program. This program was developed in the United Kingdom and licensed to South Australia in 2019. The program is currently delivered across six community locations.MethodsThe aim of this study was to explore participants perspectives of the Sporting Memories program in South Australia. Underpinned by qualitative research, three focus groups were conducted, led by an experienced interviewer. Focus groups occurred at three of the six locations, including a day respite center, assisted living center and a government community center. The data were analyzed thematically by the research team.ResultsThere were 16 participants over 65 years old, including four women and 12 men. Three key themes were developed: “free to talk about anything,” “not feeling left out” and “a chance to share and learn.” Collectively, participants reflected on how they built social connections, felt safe and included and learnt more about each other.ConclusionThe Sporting Memories program provides a group program for older people to come together and develop new friendships. The use of sports as a means of reminiscence was considered relatable for the participants who reported social benefits and plans to keep attending. They valued learning through the program which was enhanced by having a facilitator who was knowledgeable about sport.

One of the main priorities of the Integrated Care Systems (ICS) is to expand the number of ‘virtual wards’ and deliver multidisciplinary care for patients closer to home. We present to you the Specialist Neurological Rehabilitation Service (SNRS) which has demonstrated over the last 7 years that intensive neurological rehabilitation can be delivered successfully in the patients’ own homes. A novel commissioning model has been used in partnership with different NHS trusts to provide a unified neurorehabilitation service with both inpatient hospital beds and virtual beds in the patients’ own homes. While patients are on the virtual bed pathway, they remain under the care of the Consultant in Rehabilitation Medicine with support from the Clinical Nurse Specialist and have access to diagnostics/interventions and clinic reviews. The patients get daily intensive MDT therapy input from the skilled community team who provide the same frequency of therapy sessions at home (as they would get in a level 2 inpatient neurorehabilitation unit). This pathway is supporting the earlier discharge of patients from hospital. Additionally, the analysis of data from the virtual bed pathway shows that rehabilitation outcomes in patients’ own homes are similar to those of bedded units for this subset of patients with complex neurological needs. This illustrates that the virtual ward model can be successfully implemented in neurorehabilitation.

Background: Dupuytren disease is the result of a pathologic proliferation of myofibroblasts leading to the formation of dense nodules and eventually palpable cords over the palmar aspect of the hand. These cords have typical anatomic relationships in the palm and fingers and can distort local anatomy, leading to potential iatrogenic injury during surgical treatment. We report a case of a single pretendinous cord that branches into central cords of two individual fingers. Case report: A 75 year old male presents with painful contractures of the left hand involving the middle and ring fingers. A single pretendinous cord originates at the mid palm along the ring finger metacarpal and branches to the ulnar long finger and radial ring finger. The neurovascular bundles were identified in close proximity to the pathologic tissues but did not form true spiral nerve complexes. Literature review: Classic anatomic relationships for pretendinous, central, and spiral cords are well described in the literature. To our knowledge, this is the first reported case of this branching pattern to separate digits, although other branching patterns to the same digit have been previously described. Clinical relevance: The common and proper digital neurovascular bundles can be put at increased risk of injury in the surgical management of Dupuytren disease, especially in the setting of unexpected anatomic variants. It is paramount that surgeons remain vigilant in the unpredictable setting of these pathologic structures and strict adherence to their careful dissection and resection should be stressed.

Abstract In ovarian cancer, there is no current method to accurately predict recurrence after a complete response to chemotherapy. Here, we develop a machine learning risk score using serum proteomics for the prediction of early recurrence of ovarian cancer after initial treatment. The developed risk score was validated in an independent cohort with serum collected prospectively during the remission period. In the discovery cohort, patients scored as low-risk had a median time to recurrence (TTR) that was not reached at 10 years compared to 10.5 months (HR 4.66, p

Introduction Opioids and imaging are considered low-value care for most people with low back pain. Yet around one in three people presenting to the emergency department (ED) will receive imaging, and two in three will receive an opioid. NUDG-ED aims to determine the effectiveness of two different behavioural ‘nudge’ interventions on low-value care for ED patients with low back pain.Methods and analysis NUDG-ED is a 2×2 factorial, open-label, before-after, cluster randomised controlled trial. The trial includes 8 ED sites in Sydney, Australia. Participants will be ED clinicians who manage back pain, and patients who are 18 years or over presenting to ED with musculoskeletal back pain. EDs will be randomly assigned to receive (i) patient nudges, (ii) clinician nudges, (iii) both interventions or (iv) no nudge control. The primary outcome will be the proportion of encounters in ED for musculoskeletal back pain where a person received a non-indicated lumbar imaging test, an opioid at discharge or both. We will require 2416 encounters over a 9-month study period (3-month before period and 6-month after period) to detect an absolute difference of 10% in use of low-value care due to either nudge, with 80% power, alpha set at 0.05 and assuming an intra-class correlation coefficient of 0.10, and an intraperiod correlation of 0.09. Patient-reported outcome measures will be collected in a subsample of patients (n≥456) 1 week after their initial ED visit. To estimate effects, we will use a multilevel regression model, with a random effect for cluster and patient, a fixed effect indicating the group assignment of each cluster and a fixed effect of time.Ethics and dissemination This study has ethical approval from Southwestern Sydney Local Health District Human Research Ethics Committee (2023/ETH00472). We will disseminate the results of this trial via media, presenting at conferences and scientific publications.Trial registration number ACTRN12623001000695.

Summary: Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

IntroductionVeterinary biobanks store samples for future use and distribute samples to academic researchers and industry entities; however, informed consent provided by owners for pets contributing to biobanks can be complicated by limited understanding of goals, purpose, and logistics of biobanking.MethodsThis survey-based study aimed to gather feedback from pet owners on how they viewed allowing their pet to contribute to a veterinary biobank, with the goal of identifying opportunities to improve education, awareness of veterinary biobanking initiatives, and the consent processes. An electronic survey was distributed to a listserv of 2,119 pet owners and responses were received from 118 respondents (5.6%).ResultsMost respondents (67%) were not familiar with the concept of veterinary biobanking prior to having responded to the survey. Most (89%) were willing to allow their healthy pet to contribute samples to a veterinary biobanking program. Ninety-five percent would allow their sick pet to contribute. Most were neutral about financial incentives as a motivator to participate, although 40% indicated that if their pet’s condition resulted in a decision to humanely euthanize, they would be more likely to contribute to the biobank if the veterinary biobanking program covered the cost of euthanasia. Common concerns included security/confidentiality (36%), that results would not be shared with them (33%) or that samples would be used for other purposes beyond those advertised (22%).DiscussionThese results suggest veterinary biobanking initiatives are well received by owners and most are willing to allow their pets to participate. Respondent concerns represent opportunities for veterinary biobanks to improve messaging and dissemination of results from work they support.

Abstract The selection pressures that drove dramatic encephalisation processes through the mammal lineage remain elusive, as does knowledge of brain structure reorganisation through this process. In particular, considerable structural brain changes are present across the primate lineage, culminating in the complex human brain that allows for unique behaviours such as language and sophisticated tool use. To understand this evolution, a diverse sample set of humans' closest relatives with varying socio‐ecologies is needed. However, current brain banks predominantly curate brains from primates that died in zoological gardens. We try to address this gap by establishing a field pipeline mitigating the challenges associated with brain extractions of wild primates in their natural habitat. The success of our approach is demonstrated by our ability to acquire a novel brain sample of deceased primates with highly variable socio‐ecological exposure and a particular focus on wild chimpanzees. Methods in acquiring brain tissue from wild settings are comprehensively explained, highlighting the feasibility of conducting brain extraction procedures under strict biosafety measures by trained veterinarians in field sites. Brains are assessed at a fine‐structural level via high‐resolution MRI and state‐of‐the‐art histology. Analyses confirm that excellent tissue quality of primate brains sourced in the field can be achieved with a comparable tissue quality of brains acquired from zoo‐living primates. Our field methods are noninvasive, here defined as not harming living animals, and may be applied to other mammal systems than primates. In sum, the field protocol and methodological pipeline validated here pose a major advance for assessing the influence of socio‐ecology on medium to large mammal brains, at both macro‐ and microstructural levels as well as aiding with the functional annotation of brain regions and neuronal pathways via specific behaviour assessments.

Partial state of charge (PSOC) is an important use case for lead–acid batteries. Charging times in lead–acid cells and batteries can be variable, and when used in PSOC operation, the manufacturer’s recommended charge times for single-cycle use are not necessarily applicable. Knowing how long charging will take and what the variability in time required is allows for better planning of operations and algorithm creation for battery energy storage system (BESS) manufacturers. This paper details and demonstrates a procedure for identifying the charging time of cells when different charge throughputs occur prior to reaching full charge. The results showed that the charging time in PSOC operations was highly variable when a charge-factor-controlled full-charge procedure was used. Also noted were that higher voltages for the same state of charge were reached as the number of cycles following reaching full charge increased. None of the regimes tested in this paper caused any significant capacity degradation, which demonstrates that PSOC operations can be performed even on cells not specifically designed for them, provided the correct regime is chosen.

Abstract Background Breast cancer (BC) is a leading cause of premature death in women and the most expensive malignancy to treat. Since the introduction of targeted therapies has resulted in changes to BC therapy practices, health economic evaluations have become more important in this area. Taking generic medications, Aromatase Inhibitors (AIs), as a case study, we conducted a systematic review of the recent economic evaluations of AIs for estrogen receptor-positive breast cancer patients and evaluated the quality of these health economic studies. Objective To systematically review and examine the quality of the available economic studies of AIs in estrogen receptor-positive breast cancer. Methods A literature search was performed using six relevant databases (MEDLINE, Embase, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, NHS Economic Evaluation Database, and SCOPUS) from January 2010 to July 2021. All economic studies were independently assessed by two reviewers using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist to evaluate the quality of the economic evaluations. This systematic review is registered in the PROSPERO database. To compare the different currencies used in these studies, all costs were converted to international dollars (2021). Results A total of eight studies were included in the review; six (75%) were performed from the healthcare providers’ perspective. They were conducted in seven different countries, and all were model-based analyses using Markov models. Six (75%) considered both Quality Adjusted Life Years (QALYs) and Life Years (LY) outcomes, and all costs were derived from national databases. When compared to tamoxifen, AIs were generally cost-effective in postmenopausal women. Only half of the studies addressed the increased mortality following adverse events, and none mentioned medication adherence. For the quality assessment, six studies fulfilled 85% of the CHEERS checklist requirements and are deemed good quality. Conclusion AIs are generally considered cost-effective compared to tamoxifen in estrogen receptor-positive breast cancer. The overall quality of the included studies was between high and average but characterizing heterogeneity, and distributional effects should be considered in any future economic evaluation studies of AIs. Studies should include adherence and adverse effects profiles to provide evidence to facilitate decision-making among policymakers.

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.

Over the past decades, morphometric analysis of brain MRI has contributed substantially to the understanding of healthy brain structure, development and aging as well as to improved characterisation of disease related pathologies. Certified commercial tools based on normative modeling of these metrics are meanwhile available for diagnostic purposes, but they are cost intensive and their clinical evaluation is still in its infancy. Here we have compared the performance of “ScanOMetrics”, an open-source research-level tool for detection of statistical anomalies in individual MRI scans, depending on whether it is operated on the output of FreeSurfer or of the deep learning based brain morphometry tool DL + DiReCT. When applied to the public OASIS3 dataset, containing patients with Alzheimer’s disease (AD) and healthy controls (HC), cortical thickness anomalies in patient scans were mainly detected in regions that are known as predilection areas of cortical atrophy in AD, regardless of the software used for extraction of the metrics. By contrast, anomaly detections in HCs were up to twenty-fold reduced and spatially unspecific using both DL + DiReCT and FreeSurfer. Progression of the atrophy pattern with clinical dementia rating (CDR) was clearly observable with both methods. DL + DiReCT provided results in less than 25 min, more than 15 times faster than FreeSurfer. This difference in computation time might be relevant when considering application of this or similar methodology as diagnostic decision support for neuroradiologists.

Acoustic surveys for sperm whales (Physeter macrocephalus) were conducted in the Mediterranean Sea in summer 2018 as part of the vessel-based component of the ACCOBAMS Survey Initiative (ASI). Equal-spaced zigzag transects provided uniform coverage of key sperm whale habitats and were surveyed using a towed hydrophone array deployed from a research vessel at speeds of 5-8 knots. A total of 14,039 km of tracklines were surveyed in the western basin, Hellenic Trench and Libyan waters, with an acoustic coverage of 10% realised for sperm whales. During these surveys, 254 individual sperm whales were detected on the trackline, with an additional 66 individuals off-track. Sperm whales were only seen ten times on-track, with an additional 16 off-track sightings. Estimates of slant range to echolocating whales were used to derive density estimates through both design- and model-based distance sampling methodologies. An acoustic availability of 0.912 (sd = 0.036) was derived from via published models. When correcting for availability bias, a design-based abundance estimates of 2,673 individuals (95% CI 1,739-4,105; CV = 0.21) was derived for the surveyed blocks, which incorporated most known sperm whale habitat in the Mediterranean Sea. The equivalent model-based estimate was 2,825 whales (2,053-3,888; CV = 0.16). Over 97% of detected whales were in the western basin, with highest densities in the Algerian and Liguro-Provencal Basins between Algeria and Spain/France. In the eastern basin, detections were sparse and concentrated along the Hellenic Trench. A density surface modelling (DSM) exercise identified location and benthic aspect as being the most instructive covariates for predicting whale abundance. Distance sampling results were used in a power analysis to quantify the survey effort required to identify population trends. In the most extreme scenario modelled (10% per annum decline with decennial surveys), the population could have dropped by 90% before the decline was identified with high statistical power. Increasing the regularity of surveys would allow population trends to be detected more expediently. Mediterranean sperm whales are listed as Endangered on the IUCN’s Red List and the need for urgent conservation measures to reduce injury and mortality remains paramount for this unique sub-population.

Introduction Cerebrovascular disease and neurodegeneration are causes of cognitive decline and dementia, for which primary prevention options are currently lacking. Statins are well-tolerated and widely available medications that potentially have neuroprotective effects. The STAREE-Mind Imaging Study is a randomised, double-blind, placebo-controlled clinical trial that will investigate the impact of atorvastatin on markers of neurovascular health and brain atrophy in a healthy, older population using MRI. This is a nested substudy of the ‘Statins for Reducing Events in the Elderly’ (STAREE) primary prevention trial.Methods Participants aged 70 years or older (n=340) will be randomised to atorvastatin or placebo. Comprehensive brain MRI assessment will be undertaken at baseline and up to 4 years follow-up, including structural, diffusion, perfusion and susceptibility imaging. The primary outcome measures will be change in brain free water fraction (a composite marker of vascular leakage, neuroinflammation and neurodegeneration) and white matter hyperintensity volume (small vessel disease). Secondary outcomes will include change in perivascular space volume (glymphatic drainage), cortical thickness, hippocampal volume, microbleeds and lacunae, prefrontal cerebral perfusion and white matter microstructure.Ethics and dissemination Academic publications from this work will address the current uncertainty regarding the impact of statins on brain structure and vascular integrity. This study will inform the utility of repurposing these well-tolerated, inexpensive and widely available drugs for primary prevention of neurological outcomes in older individuals. Ethics approval was given by Monash University Human Research Ethics Committee, Protocol 12206.Trial registration number ClinicalTrials.gov Identifier: NCT05586750.

In 2020, the World Health Organization (WHO) reported 604,000 new diagnoses of cervical cancer (CC) worldwide, and over 300,000 CC-related fatalities. The vast majority of CC cases are caused by persistent human papillomavirus (HPV) infections. HPV-related CC incidence and mortality rates have declined worldwide because of increased HPV vaccination and CC screening with the Papanicolaou test (PAP test). Despite these significant improvements, developing countries face difficulty implementing these programs, while developed nations are challenged with identifying HPV-independent cases. Molecular and proteomic information obtained from blood or tumor samples have a strong potential to provide information on malignancy progression and response to therapy in CC. There is a large amount of published biomarker data related to CC available but the extensive validation required by the FDA approval for clinical use is lacking. The ability of researchers to use the big data obtained from clinical studies and to draw meaningful relationships from these data are two obstacles that must be overcome for implementation into clinical practice. We report on identified multimarker panels of serum proteomic studies in CC for the past 5 years, the potential for modern computational biology efforts, and the utilization of nationwide biobanks to bridge the gap between multivariate protein signature development and the prediction of clinically relevant CC patient outcomes.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Abstract Background and Aim Up to a third of patients with inflammatory bowel disease (IBD) have elevated liver enzymes (ELE). We evaluated the incidence, predictors, and outcomes associated with ELE in a diverse and vulnerable IBD cohort. Methods We retrospectively evaluated 336 IBD patients receiving care at the San Francisco safety net gastroenterology clinics between June 1996 and December 2019. Baseline characteristics were captured at first visit, then patients were followed until last clinic activity or death. Testing and etiology, pattern of ELE defined as transient (

Abstract Introduction A novel fully porous acetabular titanium shell has been designed to reduce stiffness mismatch between bone and implant and promote osseointegration in complex (cTHA) and revision total hip arthroplasty (rTHA). A highly cross-linked polyethylene (XLPE) liner is cemented within the cup to reduce wear rates and increase survivorship. This study reported the outcomes of an XLPE liner cemented into a novel 3D-printed fully porous cup in cTHA and rTHA. Methods Presented was a multicenter retrospective review of 40 patients (6 cTHA and 34 rTHA) who underwent THA with a fully porous titanium acetabular cup and cemented XLPE liner. Data were collected on demographics, surgical information, outcomes, including osseointegration and migration and implant survivorship. Results On average, patients were 71.42 ± 9.97 years old and obese (BMI: 30.36 ± 6.88 kg/m2) and were followed up for a mean time of 2.21 ± 0.77 years. Six patients underwent cTHA and 34 patients underwent rTHA. The mean hospital length of stay was 5.34 ± 3.34 days. Three (7.5%) 90-day readmissions were noted. Harris Hip Scores improved, on average, from 53.87 ± 12.58 preoperatively to 83.53 ± 12.15 postoperatively (P

Coulter et al. (2019) argue that there is an urgent need for a theoretically coherent conceptualisation of contemporary relationship-based practice (RBP) models within child and family social work. They propose that a systemic and social constructionist 'lens' can provide this coherence. This reply draws attention to one particular difficulty with their argument and makes a partial case for maintaining clear distinctions between models, with distinct nomenclature. [ABSTRACT FROM AUTHOR]

Abstract Background Null Hypothesis Significance Testing (NHST) has been well criticised over the years yet remains a pillar of statistical inference. Although NHST is well described in terms of statistical models, most textbooks for non-statisticians present the null and alternative hypotheses (H 0 and H A, respectively) in terms of differences between groups such as (μ 1 = μ 2) and (μ 1 ≠ μ 2) and H A is often stated to be the research hypothesis. Here we use propositional calculus to analyse the internal logic of NHST when couched in this popular terminology. The testable H 0 is determined by analysing the scope and limits of the P-value and the test statistic’s probability distribution curve. Results We propose a minimum axiom set NHST in which it is taken as axiomatic that H 0 is rejected if P-value< α. Using the common scenario of the comparison of the means of two sample groups as an example, the testable H 0 is {(μ 1 = μ 2) and [( $$\overline{x}$$ x ¯ 1 ≠ $$\overline{x}$$ x ¯ 2) due to chance alone]}. The H 0 and H A pair should be exhaustive to avoid false dichotomies. This entails that H A is ¬{(μ 1 = μ 2) and [( $$\overline{x}$$ x ¯ 1 ≠ $$\overline{x}$$ x ¯ 2) due to chance alone]}, rather than the research hypothesis (H T). To see the relationship between H A and H T, H A can be rewritten as the disjunction H A: ({(μ 1 = μ 2) ∧ [( $$\overline{x}$$ x ¯ 1 ≠ $$\overline{x}$$ x ¯ 2) not due to chance alone]} ∨ {(μ 1 ≠ μ 2) ∧ [ $$(\overline{x}$$ ( x ¯ 1 ≠ $$\overline{x}$$ x ¯ 2) not due to (μ 1 ≠ μ 2) alone]} ∨ {( μ 1 ≠ μ 2 ) ∧ [( $$\overline{\boldsymbol{x}}$$ x ¯ 1 ≠ $$\overline{\boldsymbol{x}}$$ x ¯ 2 ) due to ( μ 1 ≠ μ 2 ) alone]}). This reveals that H T (the last disjunct in bold) is just one possibility within H A. It is only by adding premises to NHST that H T or other conclusions can be reached. Conclusions Using this popular terminology for NHST, analysis shows that the definitions of H 0 and H A differ from those found in textbooks. In this framework, achieving a statistically significant result only justifies the broad conclusion that the results are not due to chance alone, not that the research hypothesis is true. More transparency is needed concerning the premises added to NHST to rig particular conclusions such as H T. There are also ramifications for the interpretation of Type I and II errors, as well as power, which do not specifically refer to H T as claimed by texts.