Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project.

Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms. Methods: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities. Results: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18-100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates. Conclusion: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

Large language models and agricultural extension services.

Several factors have traditionally hampered the effectiveness of agricultural extension services, including limited institutional capacity and reach. Here we assess the potential of large language models (LLMs), specifically Generative Pre-trained Transformer (GPT), to transform agricultural extension. We focus on the ability of LLMs to simplify scientific knowledge and provide personalized, location-specific and data-driven agricultural recommendations. We emphasize shortcomings of this technology, informed by real-life testing of GPT to generate technical advice for Nigerian cassava farmers. To ensure a safe and responsible dissemination of LLM functionality across farming worldwide, we propose an idealized LLM design process with human experts in the loop.

Impact of the COVID-19 pandemic on a post-mortem CT service for adult non-suspicious death.

Due to the COVID-19 pandemic, the post-mortem computed tomography (PMCT) service was expanded from three to seven cases per day to help mortuary services and avoid invasive autopsy. Additional targeted angiography and pulmonary ventilation procedures were stopped and triage rules relaxed to allow more indications to be scanned, including those requiring toxicology. A service evaluation was performed for the first 3-months of the COVID-19 pandemic compared to the equivalent period the previous year to study the impact of these changes. It was found that, despite the increase in deaths regionally, coronial referrals remained about 100 per month, a reduction in referral rate. The number undergoing PMCT rose from 28% to 74% of cases. Turnaround time remained the same. For cases triaged to PMCT, the need for subsequent autopsy increased from 7.9% to 15.8%. No significant changes were seen in diagnosis rates, including cardiac or respiratory. There was an increase in patients with coronary death without severe coronary calcification who underwent autopsy after PMCT. These may have been diagnosed by targeted coronary angiography. Fifty-three cases requiring toxicology/biochemistry had PMCT, with 38 having PMCT only. In 8/11 (72.7%) cases with normal PMCT and toxicology as the key diagnostic test, autopsy was performed prior to results. This suggests the pathology team were reluctant to risk an "unascertained" outcome. This study shows that it is possible to increase PMCT services by widening referral criteria and by limiting the use of enhanced imaging techniques, without significantly changing diagnosis rates of key diseases; however, selectively restarting targeted angiography may help avoid autopsy in some cases.

Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon.

The Healthy Oregon Project (HOP) is a statewide effort that aims to build a large research repository and influence the health of Oregonians through providing no-cost genetic screening to participants for a next-generation sequencing 32-gene panel comprising genes related to inherited cancers and familial hypercholesterolemia. This type of unbiased population screening can detect at-risk individuals who may otherwise be missed by conventional medical approaches. However, challenges exist for this type of high-throughput testing in an academic setting, including developing a low-cost high-efficiency test and scaling up the clinical laboratory for processing large numbers of samples. Modifications to our academic clinical laboratory including efficient test design, robotics, and a streamlined analysis approach increased our ability to test more than 1,000 samples per month for HOP using only one dedicated HOP laboratory technologist. Additionally, enrollment using a HIPAA-compliant smartphone app and sample collection using mouthwash increased efficiency and reduced cost. Here, we present our experience three years into HOP and discuss the lessons learned, including our successes, challenges, opportunities, and future directions, as well as the genetic screening results for the first 13,670 participants tested. Overall, we have identified 730 pathogenic/likely pathogenic variants in 710 participants in 24 of the 32 genes on the panel. The carrier rate for pathogenic/likely pathogenic variants in the inherited cancer genes on the panel for an unselected population was 5.0% and for familial hypercholesterolemia was 0.3%. Our laboratory experience described here may provide a useful model for population screening projects in other states.

The 10-year trajectory of aggressive behaviours in autistic individuals.

BACKGROUND: Aggressive behaviours are common in people with neurodevelopmental conditions, contributing to poorer quality of life and placement breakdown. However, there is limited empirical research documenting the prevalence and persistence of aggressive behaviours in autism. In this longitudinal study, aggressive behaviours were investigated in a sample of autistic individuals over 10 years. METHODS: Caregivers of autistic individuals, both with and without intellectual disability, completed questionnaires relating to the presence of aggressive behaviours at T1 [N = 229, mean age in years 11.8, standard deviation (SD) 5.9], T2 (T1 + 3 years, N = 81, mean age in years 15.1, SD 5.9) and T3 (T1 + 10 years, N = 54, mean age in years 24.5, SD 8.1). Analyses examined the presence and persistence of aggressive behaviours and the predictive value of established correlates of aggression. RESULTS: Aggressive behaviours were common at baseline (61.6%) but only persistent in 30% of the sample over 10 years. Higher composite scores of overactivity and impulsivity at T1 were significantly associated with the persistence of aggressive behaviours at T2 (P = 0.027) and T3 (P = 0.012) with medium effect size. CONCLUSIONS: Aggressive behaviours are common in autism, but reduce with age. Behavioural correlates of attention deficit hyperactivity disorder (ADHD) predict the presence and persistence of aggressive behaviour and as such may be useful clinical indicators to direct proactive intervention resources to ameliorate aggressive behaviours.

An evaluation of a novel bowel preparation regimen and its effect on the utility of colon capsule endoscopy: a prospective cohort study with historical controls.

BACKGROUND: The aim of this study was to evaluate the efficacy of a novel bowel preparation and booster regimen for colon capsule endoscopy (CCE) using macrogol, phospho-soda and gastrografin, compared with a control regimen consisting of polyethylene glycol and sodium picosulfate. METHODS: This was a prospective cohort study using historical controls. Symptomatic patients undergoing CCE between 11/07/2021 and 21/12/2021 using the novel regimen were included. Symptomatic patients who underwent CCE in the ScotCap evaluation using the control regimen were used as historical controls. We measured the rate of complete test (visualisation of the whole colon and rectum), adequate bowel preparation, successful test (complete and adequate bowel preparation) and need for further test following CCE. The rate of adverse events was also collected. RESULTS: Patients undergoing CCE using the new and control regimen were 200 and 316, respectively. The median age, age range and proportion of female patients in the new and control regimen cohorts was 61 vs 60 years, 16-86 vs 20-83 years, and 60.5% vs 56.6%. The rate of complete test, adequate bowel reparation and successful test for the new and control regimen was 69% vs 72.2%, 86.6% vs 80.7% and 60.5% vs 65.8%. Comparing the new and control regimen, 39.5% vs 37.3% of patients required no test following CCE, 26% vs 32.6% required a colonoscopy, 31.5% vs 21.5% required a flexible sigmoidoscopy and 3% vs 2.9% required a computed tomography colonogram. No adverse events were reported using the new regimen compared to 2 (0.6%) in the control group. CONCLUSIONS: The rate of adequate bowel preparation has improved following the introduction of a new regimen. However, further work is needed to increase the complete test rate. A significant proportion of patients continue to avoid colonoscopy following CCE.

Proton damage in (Y,Lu,Gd)3(Al,Ga)5O12:Ce mixed garnet scintillators.

Scintillators are vital components for nuclear instrumentation and its applications, including plasma diagnostics and imaging. As yields in controlled fusion experiments increase, the radiation tolerance of scintillator candidates for use in instrumentation is of particular importance. High radiation exposure can damage scintillating materials and alter the optical properties. The effects of radiation damage in Ce-doped mixed garnet ceramics over the compositional range (Y,Gd,Lu)3(Al,Ga)5O12 are investigated using optical techniques. The samples were exposed to 200 keV protons to an accumulated fluence of 1016 protons per square centimeter, then characterized using diffuse reflectance spectroscopy (DRS). DRS with visible light can assess the radiation tolerance of opaque poly-crystalline samples, which can be easily sintered from powders and thus offer distinct advantages in characterization compared to single crystals. Qualitative trends in induced absorption are presented as a function of composition, and the ideal cerium dopant concentration for Y2LuAl5O12 is determined to be 0.60-0.75 mol. %.

Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.

Age and the anaesthetist: considerations for the individual anaesthetist and workforce planning: Guidelines about the ageing anaesthetic workforce from the Association of Anaesthetists: Guidelines for the ageing anaesthetic workforce from the Association of Anaesthetists.

There is clear evidence of a growing workforce gap and this is compounded by demographic data that show the current workforce is ageing. Within the current workforce, more doctors are taking voluntary early retirement and the loss of these experienced clinicians from departments can have wide-ranging effects. Older doctors are at risk of age-related health problems (e.g. sight, musculoskeletal, menopause) and are more susceptible to the effects of fatigue, which may increase the risk of error and or complaint. The purpose of this working party and advocacy campaign was to address concerns over the number of consultants retiring at the earliest opportunity and whether a different approach could extend the working career of consultant anaesthetists and SAS doctors. This could be viewed as 'pacing your career'. The earlier this is considered in a clinician's career the greater the potential mitigation on individuals.

An update on oral cavity cancer: epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis.

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput 'omics' technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease.

Functional Analysis of Anuran Pelvic and Thigh Anatomy Using Musculoskeletal Modelling of Phlyctimantis maculatus.

Using their abundant musculature, frogs are able to exhibit outstanding behavioural versatility. However, understanding the dynamic motion of their 30 + hindlimb muscles, with multi-joint action, and curved pathways, is challenging. This is particularly true in walking, a relatively understudied, but complex frog gait. Building on prior musculoskeletal modelling work we construct and analyse a 3D musculoskeletal model of the spine, pelvis, and hindlimb of Phlyctimantis maculatus (previously known as Kassina maculata) to simulate the natural motion of muscle pathways as joints rotate during locomotion. Combining experimental kinematics and DICE-CT scan data we use several simulations conducted in MuJoCo to decouple femur and pelvic motions, generating new insights into the functional mechanics of walking in frogs. Outputs demonstrate pelvic lateral rotation about the iliosacral joint influences moment arm magnitude in the majority of hindlimb muscles. The extent of pelvic influence depends on femoral angle which changes muscle function in some instances. The workflow presented here can be used to help experimentalists predict which muscles to probe with in vivo techniques towards a better understanding of how anuran musculoskeletal mechanics enable multiple behaviours.

An Educational Assessment of Evidence Used for Variant Classification: A Report of the Association for Molecular Pathology.

The Association for Molecular Pathology Variant Interpretation Testing Among Laboratories (VITAL) Working Group convened to evaluate the Standards and Guidelines for the Interpretation of Sequence Variants implementation into clinical practice, identify problematic classification rules, and define implementation challenges. Variants and associated clinical information were provided to volunteer respondents. Participant variant classifications were compared with intended consensus-derived classifications of the Working Group. The 24 variant challenges received 1379 responses; 1119 agreed with the intended response (81%; 95% CI, 79% to 83%). Agreement ranged from 44% to 100%, with 16 challenges (67%; 47% to 82%) reaching consensus (≥80% agreement). Participant classifications were also compared to a calculated interpretation of the ACMG Guidelines using the participant-reported criteria as input. The 24 variant challenges had 1368 responses with specific evidence provided and 1121 (82%; 80% to 84%) agreed with the calculated interpretation. Agreement for challenges ranged from 63% to 98%; 15 (63%; 43% to 79%) reaching consensus. Among 81 individual participants, 32 (40%; 30% to 50%) reached agreement with at least 80% of the intended classifications and 42 (52%; 41% to 62%) with the calculated classifications. This study demonstrated that although variant classification remains challenging, published guidelines are being utilized and adapted to improve variant calling consensus. This study identified situations where clarifications are warranted and provides a model for competency assessment.

Artificial intelligence (AI)-assisted exome reanalysis greatly aids in the identification of new positive cases and reduces analysis time in a clinical diagnostic laboratory.

PURPOSE: Artificial intelligence (AI) and variant prioritization tools for genomic variant analysis are being rapidly developed for use in clinical diagnostic testing. However, their clinical utility and reliability are currently limited. Therefore, we performed a validation of a commercial AI tool (Moon) and a comprehensive reanalysis of previously collected clinical exome sequencing cases using an open-source variant prioritization tool (Exomiser) and the now-validated AI tool to test their feasibility in clinical diagnostics. METHODS: A validation study of Moon was performed with 29 positive cases determined by previous manual analysis. After validation, reanalysis was performed on 80 previously manually analyzed nondiagnostic exome cases using Moon. Finally, a comparison between Moon and Exomiser was completed regarding their ability to identify previously completed positive cases and to identify new positive cases. RESULTS: Moon correctly selected the causal variant(s) in 97% of manually analyzed positive cases and identified 7 new positive cases. Exomiser correctly identified the causal gene in 85% of positive cases and agreed with Moon by ranking the new gene in its top 10 list 43% of the time. CONCLUSION: The use of AI in diagnostic laboratories greatly enhances exome sequencing analysis by reducing analysis time and increasing the diagnostic rate.