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Background: As the COVID-19 pandemic began, cases of respiratory illness of unknown cause could have presented early disease signals. The detection of such signals can provide useful clues regarding disease emergence and opportunities for early outbreak control. This study assessed trends in the global incidence of reports of respiratory illness of unknown cause as early indicators of COVID-19 in late 2019, using the early warning system, EPIWATCH, to investigate the disease’s origins and early epidemiology. Methods: Global news articles published between 1-Oct and 31-Dec in 2019 and collected by EPIWATCH, an open-source Artificial Intelligence (AI)-driven epidemic surveillance system, were searched for keywords relating to unknown respiratory illness. Control periods representing the pre-COVID period (1-Oct to 31-Dec 2016-2018) were used to compare report trends over time. Data on report location, case demographics, outbreak setting, and type of illness, were extracted and descriptively analysed. Fisher’s exact tests were conducted to assess proportional differences between years. Results: Overall, 113 EPIWATCH reports of unknown respiratory illness were identified from 12 countries in 2019. Most reports (n=111 [98.2%]) were published in Northern hemisphere countries, in particular Russia (n=A72 [63.7%]) and the United States (n=17 [15.0%]). China experienced a month-on-month increase in reports. Schools were the most reported outbreak setting (n=49 [43.4%]). The proportion of included reports in 2019 was significantly higher compared to 2016-2018 (p

On June 27th, 2023, Mongolia registered its first case of bubonic plague in the Bugat settlement, Gobi-Altai province. Cases in this outbreak are widespread throughout the country with multiple close contacts identified and monitored. Environmental surveillance, including the testing of marmots, picked up the presence of Yersinia Pestis in many samples prior to the beginning of the outbreak. Marmots are seen as a delicacy in Mongolia which presents a challenge when preventing animal to human transmission of bubonic plague via the consumption of raw undercooked marmot meat. Although bubonic plague is endemic in Mongolia, cases are often sporadic and mostly registered in the western provinces of the region however, one case was recorded in the capital city of Ulan Bator on the eastern side of the country. The nature of this outbreak highlights the importance of effective preventive measures such as, PPE, awareness campaigns, health literacy and safe food handling practices.

Introduction Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.Methods and analysis SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2–6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.Ethics and dissemination The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.Trial registration number NCT04680910.

Abstract Belatedly, gastroenterologists have begun to pay attention to the role of diet in the exacerbation of gastrointestinal symptoms in many digestive disorders—a recognition that has spurred both high‐quality clinical trials and translational research into this area. It has become clear that multiple mechanisms acting either in isolation or together can induce gut symptoms and that appropriate interventions can lead to significant relief. What this review will explore is not the role of diet in the production of certain symptoms or symptom clusters, but rather whether a dietary intervention can beneficially alter the natural history of a gastrointestinal disease—a much more demanding expectation. Yet there are examples of where a diet, if sustained, can have a long‐term impact on at least some of those affected by conditions such as eosinophilic esophagitis, celiac disease, food allergy, and constipation.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Introduction Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methods In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications—ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment.Results The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular events.Conclusions While prospective studies directly assessing the predictive ability of these markers are needed, our results strengthen the role of clinical metabolomics in relation to risk assessment of diabetic complications in chronic type 1 diabetes.

Background & Aims: Infections are frequent in patients with cirrhosis and worsen prognosis. We evaluated the incidence of infections and their impact on decompensation and death in patients with early alcohol-related liver disease (ALD) during long-term follow-up. Methods: We performed a prospective cohort study of patients in secondary care with a history of excess alcohol intake, no prior decompensation, and with liver biopsies along with clinical investigations conducted at baseline. During follow-up, we reviewed the patients’ electronic healthcare records for cases of infections, hospitalizations, transient elastography measurements, decompensations, all-cause mortality, and alcohol intake. Results: We included 461 patients with a mean age of 56±10 years (76% males; fibrosis stage F0-1/F2/F3-4 = 259/107/93 [56%/23%/20%]). During a median follow-up of 4.5 years (IQR 2.9-6.3), 134 patients (29%) developed a total of 312 infections, most frequently pneumonia (106/312, 34%) and urinary tract infections (57/312, 18%). Excessive alcohol intake during follow-up, smoking ≥30 pack years, MELD score and elevated liver stiffness during follow-up were independent predictors of infections. Patients who developed at least one infection had a significantly increased risk of subsequent decompensation (hazard ratio 4.98, 95% CI 2.47-10.03) and death (hazard ratio 8.24, 95% CI 4.65-14.59). Infections increased the risk of decompensation and death independently of baseline fibrosis stage, age, gender, and MELD score. Conclusions: Almost one-third of patients with early ALD develop an infection, which worsens their prognosis by increasing the risk of decompensation and death. The risk of infections increases with liver disease severity and ongoing harmful use of alcohol. Impact and implications: This study reveals that infections significantly worsen the prognosis of patients with early alcohol-related liver disease (ALD), increasing the likelihood of decompensation and death by up to eight times. These findings, pertinent to healthcare providers, researchers, and policymakers, emphasize the importance of early prevention and management of infections in patients with ALD, even those in early stages who may be asymptomatic. It was observed that nearly one-third of patients with early-stage ALD developed infections over 4.5 years, with risk factors including alcohol overuse, smoking, and higher MELD scores. The research underscores the critical need to incorporate these insights into clinical practice and public health policies to improve patient outcomes and mitigate the impact of infections in patients with ALD.

Purpose: To evaluate the clinical and radiographic outcomes of patients who have undergone bioabsorbable screw fixation for intact, stable grade I and II osteochondritis dissecans (OCD) lesions for which at least 6 months of conservative management has failed. Methods: A retrospective review of prospectively collected data from a single institution was performed to identify patients who underwent internal fixation of stable grade I and II OCD lesions (according to the Guhl classification) between January 2010 and January 2020. Patients were included regardless of the presence of concomitant procedures. The inclusion criteria consisted of (1) primary surgery, (2) failure of at least 6 months of conservative management, (3) the use of a bioabsorbable screw (or screws), and (4) minimum 2-year clinical follow-up. Radiographs were obtained at a minimum of 1 year postoperatively. Patient demographic characteristics, clinical patient-reported outcomes, complications, and failure rates were noted. Results: Twenty-four knees among 23 patients (96% follow-up) were analyzed and followed up for 6.36 ± 3.42 years (range, 2.0-12.7 years). Patients showed statistically significant postoperative improvements in all patient-reported outcomes including the Lysholm score, International Knee Documentation Committee score, and Knee Injury and Osteoarthritis Outcome Score subscales (P < .05). In 3 knees (12%), a reoperation was required due to failure at an average of 3.64 years after the index procedure. No specific complications were attributed to the use of bioabsorbable screws. Patients in whom primary surgical treatment failed did not differ in demographic characteristics, arthroscopic findings, or surgical treatment from those who had successful treatment. Conclusions: Internal fixation of stable grade I and II OCD lesions with bioabsorbable screws produces reliable results with a 12% rate of failure in appropriately indicated patients in whom at least 6 months of conservative management has failed. Clinical outcomes improved significantly during the mid-term follow-up period. Level of Evidence: Level IV, therapeutic case series.

Cognitive health is a significant concern for people aging with HIV/AIDS. Psychosocial group therapies may help people aging with HIV who experience cognitive challenges cope with their symptoms. The COVID-19 pandemic revealed in-person group therapies need adaptation for technology-mediated delivery. Peer-led focus groups discussed adapting cognitive remediation group therapy (CRGT) as an online intervention. CRGT combines mindfulness-based stress reduction and brain training activities. Purposive sampling recruited people aging with HIV (40+) who self-identified cognitive concerns and resided in one of two Canadian provinces. Thematic content analysis was employed on transcripts by seven independent coders. Ten, 2-hour focus groups were conducted between August and November 2022. Participants (n=45) responded favorably to CRGT's modalities. Alongside support for its continued implementation in-person, participants requested online synchronous and online asynchronous formats. Preferred intervention facilitators were peers and mental health professionals. We also discuss how to adapt psychosocial HIV therapies for technology-mediated delivery.

Advanced Air Mobility (AAM), the use of drones for the delivery of goods and for transport of passengers, is an emerging mode of transportation. However, numerous challenges remain before AAM on a commercial scale will be a reality. AAM forces changes to the current air transportation system and governments globally are tasked with formulating new policies and regulations. In this work, we evaluate AAM policies from four different countries by utilising a case study approach and comparing those to emerging policies in Australia. We found that approaches differ between very comprehensive frameworks to simple, more general regulation. Results also show that Australia can learn a lot from Dubai’s example. In summary, these findings suggest that AAM policy development globally is in its infancy and provide insights into possible future pathways for AAM policy development in Australia and beyond.

Personal values influence goals and motivate actions. The case study reported in this paper explored whether an understanding of values would provide a useful framework to guide the co-creation of the undergraduate cognitive psychology curriculum at a UK University. A design team composed of staff and students ran two co-creation workshops to explore underlying values. These values were translated into curriculum ideas which were then shared via an online survey to students and staff for feedback. The activities revealed a set of values that were salient when imagining future curriculum designs: feeling stimulated, choice and autonomy, developing competence, feeling safe and secure, community and fairness. In addition, a deeper value layer was visible which reflected participants' orientations to learning and education. We describe our process for eliciting values and the intertwined and iterative relationship between value elicitation and a co-created curriculum. We also reflect on the position of co-creation within the value landscape of higher education and the social dynamics of staff-student partnerships. We argue that whilst using values to frame co-creation allows for deeper insight into how to embed curriculum re-innovation, it is important to attend to the value system of co-creation and those who do not participate.

The United Kingdom’s Medicines and Medical Devices Act (MMD Act) 2021 received royal assent on 11 February 2021. In its passage through parliament, as well as in the accompanying Explanatory Notes, the Act was framed by the government as a necessary post-Brexit bill. Yet prior to this, it was widely presumed that existing statutory instruments, enacted in 2019 to address medical devices regulation in anticipation of a ‘No Deal Brexit’, would provide the United Kingdom (UK) with the necessary legal framework through the transition period and beyond. The European Union (EU) exit legislation included provisions aimed at aligning domestic law with the new EU Medical Devices Regulation (EU MDR) and In Vitro Devices Regulation (EU IVDR) (which were initially due to be implemented during the EU exit transition period). However, just over a year later, at the end of 2020, while the 2021 Act was in the final stages of its parliamentary journey, legislation was introduced that reversed the provisions of the domestic medical device regulations concerning alignment for Great Britain (GB: England, Wales, and Scotland). The result is that the UK now has a dual system of regulation, with Northern Ireland (NI) being governed by the new EU MDR and EU IVDR and GB by older pre-Brexit (yet still EU-derived) law. This article is an attempt to analyse the complex situation now in existence regarding the regulation of medical devices in the UK. To this end, we focus on three main issues. First, we examine the difficulties and challenges presented by the dual system of regulation between NI and GB, highlighting the potentially far-reaching consequences of regulatory divergence between different UK jurisdictions. Second, we ask whether, in the rush to new legislation in 2021, opportunities to properly reform the approach to medical devices were missed. Finally, we look to the future, focusing on the recent Medicine and Healthcare products Regulatory Agency Consultation on the future of medical devices regulation in the UK and the challenges and opportunities that remain.

The symposium in this issue of Law, Technology and Humans brings together a range of scholars looking at the broad question of where next for medical devices regulation in the European Union (EU) and the United Kingdom (UK). Initially arising out of a workshop held in September 2022,[1] our motivation for the symposium is rooted in the challenges raised by what has been a significant period of change in both the EU and the UK when it comes to medical devices regulation.

Abstract Background Owner comprehension is vital to recruitment and study success, but limited information exists regarding the readability of public‐facing veterinary clinical trial descriptions. Objectives The current study sought to evaluate the readability of public‐facing online veterinary clinical trial descriptions from academic institutions and private referral practices. Animals None. Methods This prospective study assessed readability in a convenience sample of veterinary clinical trial study descriptions using 3 common methods: the Flesch‐Kincaid Grade Level (F‐K), Flesch Reading Ease Score (FRES), and online Automatic Readability Checker (ARC). Results were compared across specialties and between academic and private institutions. Results Grade level and readability consensus scores (RCSs) were obtained for 61 online clinical trial descriptions at universities (n = 49) and private practices (n = 12). Average grade‐level RCS for study descriptions was 14.13 (range, 9‐21). Using Microsoft Word, the FRES score was higher in descriptions from universities compared to private practices (P = .03), and F‐K scores were lower in university compared to private practice descriptions (P = .03). FRES (P = .07), F‐K (P = .12), and readability consensus (P = .17) scores obtained from ARC were not different between institution types. Forty‐eight studies (79%) had RCSs over 12, equivalent to reading material at college or graduate school levels. Conclusions and Clinical Importance Similar to other areas in veterinary communication, the evaluated veterinary clinical trial descriptions used for advertising and recruitment far exceeded the recommended 6th‐grade reading level for medical information. Readability assessments are straightforward to conduct, and ensuring health literacy should be a customary best practice in veterinary medicine and clinical research.

ABSTRACT: Restricting milk or milk replacer (MR) fed to dairy calves to 10% of body weight at 12.5% total solids (TS) concentration is a common feeding strategy that promotes early weaning and lowers total feed costs for raising young calves. However, this strategy has been associated with inferior performance and compromised welfare. Because a restricted liquid nutrition plan limits calf growth due to limited supply of nutrients, research on increased supply of nutrients from liquid has shown improved growth, health, and welfare of calves. Nutrient supply may be increased by feeding larger amounts of milk or MR averaging 12.5% TS, or by increasing TS above the usual 12.5% TS by increasing MR TS concentration alone (TS+), or by increasing TS concentration and volume simultaneously (TSV+). The objective of this review is to discuss liquid nutrition plans with greater TS concentration in MR or in milk diets, considering the effects of such strategies on performance and digestive tract development before weaning and the future performance of dairy calves. This review will focus on liquid nutrition plans that are based on increased TS concentration (i.e., TS+ or TSV+); therefore, enhanced liquid nutrition plans based only on increased volumes will not be the discussed. Improved growth rates have been observed in calves fed TSV+ programs. However, reduced starter intake preweaning can also have negative effects on dry matter intake, average daily gain, and digestibility postweaning. Feeding a TS+ program may reduce impairment of starter intake and therefore have positive effects on performance, nutrient digestibility, and health. When considering an accelerated nutrition plan with TS+ or TSV+, it is important to consider osmolality of the liquid diet. Further studies are necessary to confirm this hypothesis and the cost-benefit of alternative liquid nutrition plans, as well as the optimal TS concentration of milk or MR fed to dairy calves.

Introduction and aim: In recent years, probiotics have been used in functional gastrointestinal disorders, including chronic constipation (CC). The effect of Bifidobacterium infantis strain 35624 on the gut microbiota of CC patients has not been previously studied.Our aim was to analyze the fecal microbiota of constipated patients, before and after consuming a single-strain probiotic (B. infantis strain 35624). Materials and methods: We used 16S rRNA gene high-throughput sequencing to analyze the fecal microbiota of female patients (n = 13) with CC. Patients were instructed to ingest one capsule of Alflorex® (containing 1 × 109 CFUs/g B. infantis strain 35624) daily for eight weeks. Fecal samples were obtained at the baseline and end (final) of probiotic administration. Results: Alpha diversity metrics did not differ between the baseline and final periods. The butyrate producer, Oscillospira, was the taxon most strongly correlated with amplicon sequence variants (R2 = 0.55, p

Resumen: Introducción y objetivo: En los últimos años, los probióticos se han utilizado en trastornos gastrointestinales funcionales, incluido el estreñimiento crónico (EC). El efecto de la cepa 35624 de Bifidobacterium infantis sobre la microbiota intestinal de pacientes con EC no se ha estudiado previamente.Nuestro objetivo fue analizar la microbiota fecal de pacientes estreñidos antes y después de consumir un probiótico de una sola cepa (B. infantis cepa 35624). Material y métodos: Usamos secuenciación de alto rendimiento del gen 16S ARNr para analizar la microbiota fecal de pacientes mujeres (n = 13) con EC. Se indicó a los pacientes que consumieran una cápsula de Alflorex® (con 1 × 109 UFC/g de B. infantis 35624) al día durante 8 semanas. Se obtuvieron muestras fecales al inicio del estudio y al final de la administración de probióticos. Resultados: Las métricas de diversidad alfa no fueron diferentes entre la línea de base y la final. El productor de butirato Oscillospira fue el taxón más fuertemente correlacionado con las variantes de secuencia de amplicones (R2 = 0.55, p

Abstract Background Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences. Methods We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects. Results Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers. Conclusions These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.

Abstract Background Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide has been shown to induce beneficial changes in the lipid profile and reduce the risk of CVD. Reducing lipotoxic lipids with an antidiabetic drug therapy could be a path towards precision medicine approaches for the treatment of complications to diabetes. In this post-hoc study, an investigation was carried out on the effect of liraglutide on CVD-risk associated ceramides in two randomized clinical trials including participants with type 2 diabetes (T2D). Methods This study analyzed plasma samples from two independent randomized placebo-controlled clinical trials. The first trial, Antiproteinuric Effects of Liraglutide Treatment (LirAlbu12) followed a crossover design where 27 participants were treated for 12 weeks with either liraglutide (1.8 mg/d) or placebo, followed by a four-week washout period, and then another 12 weeks of the other treatment. The second clinical trial, Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LiraFlame26), lasted for 26 weeks and followed a parallel design, where 102 participants were randomized 1:1 to either liraglutide or placebo. Heresix prespecified plasma ceramides were measured using liquid chromatography mass spectrometry and assessed their changes using linear mixed models. Possible confounders were assessed with mediation analyses. Results In the LiraFlame26 trial, 26-week treatment with liraglutide resulted in a significant reduction of two ceramides associated with CVD risk, C16 Cer and C24:1 Cer (p

Abstract Background Symbiotic nitrogen fixation differs among Bradyrhizobium japonicum strains. Soybean inoculated with USDA123 has a lower yield than strains known to have high nitrogen fixation efficiency, such as USDA110. In the main soybean-producing area in the Midwest of the United States, USDA123 has a high nodule incidence in field-grown soybean and is competitive but inefficient in nitrogen fixation. In this study, a high-throughput system was developed to characterize nodule number among 1,321 Glycine max and 69 Glycine soja accessions single inoculated with USDA110 and USDA123. Results Seventy-three G. max accessions with significantly different nodule number of USDA110 and USDA123 were identified. After double inoculating 35 of the 73 accessions, it was observed that PI189939, PI317335, PI324187B, PI548461, PI562373, and PI628961 were occupied by USDA110 and double-strain nodules but not by USDA123 nodules alone. PI567624 was only occupied by USDA110 nodules, and PI507429 restricted all strains. Analysis showed that 35 loci were associated with nodule number in G. max when inoculated with strain USDA110 and 35 loci with USDA123. Twenty-three loci were identified in G. soja when inoculated with strain USDA110 and 34 with USDA123. Only four loci were common across two treatments, and each locus could only explain 0.8 to 1.5% of phenotypic variation. Conclusions High-throughput phenotyping systems to characterize nodule number and occupancy were developed, and soybean germplasm restricting rhizobium strain USDA123 but preferring USDA110 was identified. The larger number of minor effects and a small few common loci controlling the nodule number indicated trait genetic complexity and strain-dependent nodulation restriction. The information from the present study will add to the development of cultivars that limit USDA123, thereby increasing nitrogen fixation efficiency and productivity.

Abstract Background Perineal trauma, involving either naturally occurring tears or episiotomy, is common during childbirth but little is known about its psychological impact. This study aimed to determine the associations between childbirth related perineal trauma and psychological outcomes reported by women three months after giving birth and to explore factors that could mediate relationships between perineal trauma and maternal psychological outcomes. Methods This study was a secondary analysis of data from a cross-sectional population-based survey of maternal and infant health. A total of 4,578 women responded to the survey, of which 3,307 had a vaginal birth and were eligible for inclusion into the analysis. Symptoms of depression, anxiety, and post-traumatic stress (PTS) symptoms were assessed using validated self- report measures. Physical symptoms were derived from a checklist and combined to produce a composite physical symptoms score. Regression models were fitted to explore the associations. Results Nearly three quarters of women experienced some degree of perineal trauma. Women who experienced perineal trauma reported having more postnatal physical symptoms (adjusted proportional odds ratio 1.47, 95%CI 1.38 to 1.57, p-value

Abstract Introduction Singapore relies heavily on migrant workers to build its country and harbours a relatively large population of these workers. Importantly, tuberculosis (TB) remains a pernicious threat to the health of these workers and in line with the United Nations High-Level Meeting in 2023, this paper aims to uncover the qualitative discourse facing migrant workers’ uptake of TB services and provide policy recommendations to enable more equitable access to TB services for this population. Methods In-depth interviews were carried out with the migrant worker population recruited from a non-governmental organisation in Singapore that serves migrant workers through the provision of primary healthcare services, counselling, and social assistance. Interviews stopped once thematic saturation was achieved and no new themes and subthemes were found. Results A total of 29 participants were interviewed, including 16 Bangladeshis and 13 Chinese, aged between 22 and 54 years old, all worked in the construction sector. Four key themes emerged. They are (1) General TB knowledge: Misconceptions are prevalent, where we found that participants were aware of the disease but did not possess a clear understanding of its pathophysiology and associated health effects, (2) Contextual knowledge and perception of associated policies related to TB in Singapore: low awareness among migrant workers as participants’ accounts depicted a lack of information sources in Singapore especially on issues related to healthcare including TB, (3) Attitude to towards TB: Motivation to seek treatment is underpinned by ability to continue working and (4) Stigma: mixed perception of how society views TB patients. The gaps identified in migrant workers’ TB knowledge, their attitude towards the disease and their perception of the availability of TB-related services is despite Singapore’s efforts to curb community spread of TB and its proactive initiatives to reduce the prevalence. Conclusion Our study illuminates the various aspects that policymakers need to home in on to ensure this vulnerable group is sufficiently supported and equitably cared for if they develop active TB during their stay in Singapore as they contribute to the nation’s economy. Leveraging the COVID-19 pandemic as a window of opportunity to improve overall healthcare access for vulnerable groups in Singapore can be a starting point.

Societal Impact Statement Citrus are intrinsically connected to human health and culture, preventing human diseases like scurvy and inspiring sacred rituals. Citrus fruits come in a stunning number of different sizes and shapes, ranging from small clementines to oversized pummelos, and fruits display a vast diversity of flavors and aromas. These qualities are key in both traditional and modern medicine and in the production of cleaning and perfume products. By quantifying and modeling overall fruit shape and oil gland distribution, we can gain further insight into citrus development and the impacts of domestication and improvement on multiple characteristics of the fruit. Summary Citrus come in diverse sizes and shapes, and play a key role in world culture and economy. Citrus oil glands in particular contain essential oils which include plant secondary metabolites associated with flavor and aroma. Capturing and analyzing nuanced information behind the citrus fruit shape and its oil gland distribution provide a morphology‐driven path to further our insight into phenotype–genotype interactions. We investigated the shape of citrus fruit of 51 accessions based on 3D X‐ray computed tomography (CT) scan reconstructions. Accessions include members of the three ancestral citrus species as well as related genera, and several interspecific hybrids. We digitally separate and compare the size of fruit endocarp, mesocarp, exocarp, and oil gland tissue. Based on the centers of the oil glands, overall fruit shape is approximated with an ellipsoid. Possible oil gland distributions on this ellipsoid surface are explored using directional statistics. There is a strong allometry along fruit tissues; that is, we observe a strong linear relationship between the logarithmic volume of any pair of major tissues. This suggests that the relative growth of fruit tissues with respect to each other follows a power law. We also observe that on average, glands distance themselves from their nearest neighbor following a square root relationship, which suggests normal diffusion dynamics at play. The observed allometry and square root models point to the existence of biophysical developmental constraints that govern novel relationships between fruit dimensions from both evolutionary and breeding perspectives. Understanding these biophysical interactions prompts an exciting research path on fruit development and breeding.

BackgroundHealthcare organizations want to improve patient care experiences. Some use 'shadow coaching' to improve interactions between providers and patients. A Federally Qualified Health Center (FQHC) implemented a half-day observation of individual primary-care providers by a 'shadow coach' during real-time patient visits, including an in-person verbal debrief afterwards and a written report with specific recommendations. Shadow coaching identified areas for improvement. We aimed to characterize lessons and barriers to implementing shadow coaching as a mechanism to improve interactions with patients and change organizational culture.MethodsWe examined provider and coach perceptions of shadow coaching through interviewing coached providers, stratified by provider type and Consumer Assessment of Healthcare Providers and Systems (CAHPS) performance, and the coaches who coached the most providers. We interviewed 19 coached providers and 2 coaches in a large, urban FQHC. Content analysis identified implementation barriers, facilitators and themes.ResultsCoaches reported needing 'buy-in' throughout the organization and the need to be credible and empathize with the providers being coached. Most providers reported behaviour changes based on recommendations. Almost all providers recalled at least one coaching recommendation that was actionable. Providers and coaches highlighted patient-level and practise-level barriers that impeded their ability to implement recommended improvements. CAHPS data was reported as an effective performance management metric for measuring change, counselling providers, and evaluating provider-level efforts but was not always specific enough to yield tangible recommendations.ConclusionsRegular messaging by leadership about the priority and purpose of shadow coaching was essential for both physician engagement and its mature implementation across the organization. Coaching could be embedded into a long-term strategy of professional development with periodic re-coaching. Re-coaching sessions could target issues raised by providers, such as dealing with difficult patients or specific populations. Research on the timing and content of re-coaching is needed.

Interprofessional practice between speech and language therapists and teachers involve sharing knowledge and experiences to achieve a common goal of improving child outcomes. Although interprofessional practice has widespread support from both disciplines, it is not always easily implemented in day-to-day practice and numerous challenges have been documented. This study attempts to address these challenges through an epistemological perspective of interprofessional practice between teachers and speech and language therapists. Action research methodology was employed for this inquiry that spanned the duration of a school year. Data analysis placed an explicit focus on the experiences of interprofessional practice between the speech and language therapist and teachers, including an examination of how action was agreed and the processes underpinning collaborative working. An epistemological lens facilitated a more in-depth consideration of the diverse ways of knowing implicit in interprofessional practice and provided guidance on how to overcome the barriers, and realise the potential, of collaboration between speech and language therapists and teachers in daily practice. Four factors, rooted in an epistemological perspective, were generated from the analyses as core tenets of effective interprofessional practice. These included securing a participatory space; actively facilitating power-sharing; balancing the status of practical knowing with propositional knowing and anchoring interprofessional practice in collaboratively designed, practical activities that integrate ways of knowing. The former four factors, and their implications, offer concrete and practical direction for practitioners and educators on how to achieve effective interprofessional practice to help improve child outcomes collaboratively.

Background: Continuing education programs for teachers seek to enhance outcomes for participants and their students. Experiential wilderness-based programs offer outdoor-recreational activities and experiential teaching initiatives. Research needs to be conducted to reveal how they influence individual behaviors. Purpose: This research investigated whether a wilderness-based program influenced individual beliefs and confidence in using experiential teaching methods within a classroom. Methodology/Approach: A pre-, post-, and follow-up closed survey was administered to educators who had participated in the North Carolina Outward Bound Educators Initiative (NCOBEI) 2017-2018. Furthermore, retrospective follow-up surveys were administered to alumni (years 2007-2016). Responses were analyzed to determine how participants integrated learning within the classroom. Findings/Conclusions: Participation positively influenced educators' beliefs, confidence, and intentions to implement experiential techniques within the classroom immediately following the experience, although the benefits diminished over time. Educator beliefs and confidence were poor predictors of using experiential learning in the classroom. Implications: Experiential wilderness-based professional development (PD) has the potential to positively build confidence and skills for use in the classroom. PD and future research should address how to perpetuate the influence of wilderness-based continuing PD programs at the individual and institutional levels.

BackgroundHealth care organizations strive to improve patient care experiences. Some use one-on-one provider counseling (shadow coaching) to identify and target modifiable provider behaviors.ObjectiveWe examined whether shadow coaching improves patient experience across 44 primary care practices in a large urban Federally Qualified Health Center.Research designSeventy-four providers with "medium" (ie, slightly below average) overall provider ratings received coaching and were compared with 246 uncoached providers. We fit mixed-effects regression models with random effects for provider (level of treatment assignment) and fixed effects for time (linear spline with a knot and "jump" at coaching date), patient characteristics and site indicators. By design, coached providers performed worse at selection; models account for the very small (0.2 point) regression-to-the-mean effects. We assessed differential effects by coach.SubjectsA total of 46,452 patients (from 320 providers) who completed the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) Visit Survey 2.0.MeasuresCAHPS overall provider rating and provider communication composite (scaled 0-100).ResultsProviders not chosen for coaching had a nonsignificant change in performance during the period when selected providers were coached. We observed a statistically significant 2-point (small-to-medium) jump among coached providers after coaching on the CAHPS overall provider rating and provider communication score. However, these gains disappeared after 2.5 years; effects differed by coach.ConclusionsShadow coaching improved providers' overall performance and communication immediately after being coached. Regularly planned shadow coaching "booster" sessions might maintain or even increase the improvement gained in patient experience scores, but research examining additional coaching and optimal implementation is needed.

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single-molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation and neurite orientation dispersion and density imaging diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 versus 0.57, difference 0.036, 95% CI: 0.029-0.043, P < 0.001). Lesion volume (Spearman's rho rs= 0.38, P < 0.001) and g-ratio (rs= 0.24, P < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) [11/23 (48%) versus 2/15 (13%), P < 0.05]. These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity and help to identify individuals with a high degree of axonal damage at disease onset.

Based on interviews with big data researchers at UC Berkeley as part of an Ithaka S+R project, this local report provides insights on researcher practices and challenges in six thematic areas: data collection & processing; analysis: methods, tools, infrastructure; research outputs; collaboration; training; and balancing domain vs data science expertise. The report makes several recommendations based on these findings. A summary post with the recommendations is available at https://update.lib.berkeley.edu/2021/10/04/big-data-as-a-way-of-life/.

ObjectivesQuality improvement (QI) requires data, indicators, and national benchmarks. Knowledge about the usefulness of Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child HCAHPS) data are lacking. We examined quality leader and frontline staff perceptions about patient experience measurement and use of Child HCAHPS data for QI.MethodsWe surveyed children's hospital leaders and staff about their use of Child HCAHPS for QI, including measures from other studies. We compared scale and item means for leaders and staff and compared means to other studies.ResultsAlmost all leaders, but only one-third of staff, received reports with Child HCAHPS data. Leaders found the data more useful for comparisons to other hospitals than did staff. Both agreed on the validity of Child HCAHPS scores and used these data for improving pediatric care experiences. They agreed the data accurately reflect their hospital's quality of care, provide specific information for QI, and can be used to improve pediatric care experiences. They also agreed on approaches to improve Child HCAHPS scores. Among staff, QI was reported as essential to their daily work and that Child HCAHPS data were integral to QI.ConclusionsAs uptake of the Child HCAHPS survey increases, our study of one medium-sized, urban children's hospital revealed that leaders and staff believe Child HCAHPS provides actionable metrics for improvement. Our study fills a gap in research about the use of Child HCAHPS for pediatric QI. A multisite evaluation would provide further information about how the Child HCAHPS survey can improve care.

Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97-1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10-12) but not in the rest of breast cancer subtypes.

We are now in an era of molecular medicine, where specific DNA alterations can be used to identify patients who will respond to specific drugs. However, there are only a handful of clinically used predictive biomarkers in oncology. Herein, we describe an approach utilizing in vitro DNA and RNA sequencing and drug response data to create TreAtment Response Generalized Elastic-neT Signatures (TARGETS). We trained TARGETS drug response models using Elastic-Net regression in the publicly available Genomics of Drug Sensitivity in Cancer (GDSC) database. Models were then validated on additional in-vitro data from the Cancer Cell Line Encyclopedia (CCLE), and on clinical samples from The Cancer Genome Atlas (TCGA) and Stand Up to Cancer/Prostate Cancer Foundation West Coast Prostate Cancer Dream Team (WCDT). First, we demonstrated that all TARGETS models successfully predicted treatment response in the separate in-vitro CCLE treatment response dataset. Next, we evaluated all FDA-approved biomarker-based cancer drug indications in TCGA and demonstrated that TARGETS predictions were concordant with established clinical indications. Finally, we performed independent clinical validation in the WCDT and found that the TARGETS AR signaling inhibitors (ARSI) signature successfully predicted clinical treatment response in metastatic castration-resistant prostate cancer with a statistically significant interaction between the TARGETS score and PSA response (p = 0.0252). TARGETS represents a pan-cancer, platform-independent approach to predict response to oncologic therapies and could be used as a tool to better select patients for existing therapies as well as identify new indications for testing in prospective clinical trials.

ObjectivesTo examine how primary care practices use the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey and its patient-centered medical home (PCMH) items during their PCMH transition.Study designQualitative study of practices' use of patient experience data during PCMH transformation, based on a random sample of primary care practices engaged in PCMH transformation, stratified by region, practice size, PCMH recognition history, and use of the CAHPS PCMH survey.MethodsWe interviewed 105 practice leaders from 294 sampled practices (36% response rate) and used content analysis to identify themes about uses of patient experience data for practice improvement during PCMH transformation.ResultsPatient experience data were used primarily to assess and track improvements toward PCMH goals and as quality improvement (QI) metrics. CAHPS measures were used most often to discuss best practices, share data with patient advisory councils, and improve provider performance. The CAHPS PCMH survey helped practices improve patient-centeredness, particularly in coordinating care and supporting patient self-management and communication. The CAHPS PCMH items that assisted practices most were about patient self-management and provider referrals. Most practice leaders using the CAHPS PCMH survey felt that its items were actionable for standardizing PCMH changes or making structural changes. Practices administering CAHPS surveys focused on a more diverse set of QI areas.ConclusionsCAHPS surveys were considered actionable for PCMH transformation and used in standardizing and coordinating care. The CAHPS PCMH items were considered integral to the continuous QI needed for moving beyond formal PCMH recognition and maximizing transformation. This supports the National Committee for Quality Assurance's recommendation to administer the CAHPS or CAHPS PCMH survey for PCMH transformation.