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Research has found that psychological groups based on opinion congruence are an important group type. Previous research constructed such groups around opinions potentially connected to pre-existing identities. We strip away the socio-structural context by using novel opinions to determine whether opinion congruence alone can be a category cue which can foster identification and whether such group identification mediates the relationship between opinion exposure and opinion polarization. We assess this across two pre-registered online interactive experiments. Study 1 (N = 1168) demonstrate that opinion congruence fostered stronger identity than minimal groups. Study 2 (N = 505) demonstrate that opinion congruence fostered stronger identification than non-opinion congruence. The relationship between opinion exposure and opinion polarization occurs through group identification in both. Results demonstrate that (novel) opinions can be self-categorization cues informing identification and influencing opinion polarization., (© 2024 The Author(s). British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

The increasing burden of chronic kidney disease (CKD) on the health care system highlights the need to prioritize services and manage the use of resources efficiently. Amid these financial constraints, key decision makers must weigh the impact of an intervention or program on health care expenditure when determining the allocation of limited resources. Patient-reported outcome measures (PROMs) are relevant in health economic decision-making within nephrology. Health-related quality of life, a patient-reported outcome, can provide data that inform economic evaluations of treatments for patients with CKD. PROMs help determine the value of different therapies by assessing their impact on patients' daily lives beyond clinical outcomes and can help policymakers make decisions about funding and reimbursement that consider the priorities and preferences of patients. Economic evaluations often employ cost-utility analyses, which use quality-adjusted life years as a key metric. Quality-adjusted life years combine both the quality and quantity of life lived, allowing for comparison of the effectiveness of different interventions in a standardized manner. By integrating utilities derived from PROMs, these analyses quantify the benefits of CKD treatments in terms of how patients feel and function. Furthermore, PROMs contribute to quality improvement initiatives by identifying areas where patient care can be enhanced, guiding the implementation of programs that improve health-related quality of life while maintaining cost-effectiveness. In value-based financing environments, the integration of PROMs ensures that patient-centered outcomes are prioritized, leading to more effective and equitable health care delivery. In this article, we discuss the role of PROMs in economic evaluations in CKD and provide an overview of approaches for using PROMs in economic evaluations to inform decision-making in nephrology., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Food marketing in television and digital media negatively affects appetitive sensations and eating behaviour in children, but effects are less well understood for outdoor food advertising and adults. This research used Ecological Momentary Assessment (EMA) to explore associations between exposures to food advertising in various contexts (television, digital, outdoors) and adults' hunger and craving for highly advertised food categories. Over one week, participants provided ratings of cravings for types of food (fast food, soft drinks, snacks/confectionery, other) and hunger on a smartphone app up to six times per day when they saw a food advertisement (reactive assessment) and at random intervals (random assessment). Fifty-four participants (70.4 % female; 21.24 ± 3.84 years) provided 1223 assessments (24.7 % reactive, 75.3 % random). Data were analysed in R using multilevel multivariable linear regression models. Participants reported feeling hungrier (X 2 (1) = 5.85, p = .016, ΔAIC = 3.9) and having stronger cravings (X 2 (1) = 20.64, p < .001, ΔAIC = 318.6) after seeing food advertisements vs. random assessments. This was driven by greater hunger following television advertising exposure vs. random assessments (β = 1.58, SE = 0.61, p = .010, 95 %CIs 0.38 to 2.78), food advertising via digital devices or outdoors was not associated with hunger. Participants experienced stronger craving after seeing a food advertisement on television (β = 0.52, SE = 0.19, p = .006, 95 %CIs 0.15 to 0.89), outdoors (β = 0.39, SE = 0.12, p < .001, 95 % CIs 0.16 to 0.62) and in digital media (β = 0.36, SE = 0.14, p = .012, 95 % CIs 0.08 to 0.64), vs. random assessments. Cravings were (largely) specific to the advertised food category. EMA can be effective for assessing food marketing associations in adults. The current study provides evidence that food marketing is associated with hunger and craving in adults, which may, with replication, have implications for public health policy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul Christiansen reports a relationship with the American Beverage Association that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with neurocognitive disorders often battle sleep disturbances. Kynurenic acid is a tryptophan metabolite of the kynurenine pathway implicated in the pathology of these illnesses. Modest increases in kynurenic acid, an antagonist at glutamatergic and cholinergic receptors, result in cognitive impairments and sleep dysfunction. We explored the hypothesis that inhibition of the kynurenic acid synthesising enzyme, kynurenine aminotransferase II, may alleviate sleep disturbances. At the start of the light phase, adult male and female Wistar rats received systemic injections of either: (i) vehicle; (ii) kynurenine (100 mg kg -1 ; i.p.); (iii) the kynurenine aminotransferase II inhibitor, PF-04859989 (30 mg kg -1 ; s.c.); or (iv) PF-04859989 and kynurenine in combination. Kynurenine and kynurenic acid levels were evaluated in the plasma and brain. Separate animals were implanted with electroencephalogram and electromyogram telemetry devices to record polysomnography, and evaluate the vigilance states wake, rapid eye movement sleep and non-rapid eye movement sleep following each treatment. Kynurenine challenge increased brain kynurenic acid and resulted in reduced rapid eye movement sleep duration, non-rapid eye movement sleep delta power and sleep spindles. PF-04859989 reduced brain kynurenic acid formation when given prior to kynurenine, prevented disturbances in rapid eye movement sleep and sleep spindles, and enhanced non-rapid eye movement sleep. Our findings suggest that reducing kynurenic acid in conditions where the kynurenine pathway is activated may serve as a potential strategy for improving sleep dynamics., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

We assess the strategic alignment of attitudes and the active construction of attitude-based identity across two studies. Study one assessed the twitter response (hashtags in English) to the war in Ukraine for five months after Russia's first invasion of Ukraine 2022 (N = 8149). Results demonstrated that individuals publicly expressed hashtags similar to others close to them in the followership network, showing their support for Ukraine and condemnation of the Russian invasion in qualitatively different ways. Study two was a preregistered Prolific experiment with geographical European participants ran in September, 2022 (N = 1368). Results demonstrated that attitude interaction with ingroup members motivated interactants towards attitude alignment, and attitude alignment strengthened the identification that motivated the alignment in the first place. Results suggest that attitude expression is performative and constrained by one's group relationship with one's audience and the definition of social identity can be constrained by opinion-based identity performance., (© 2024. The Author(s).)

Background: CAR T cell therapy is a promising approach to improve outcomes and decrease toxicities for patients with cancer. While extraordinary success has been achieved using CAR T cells to treat patients with CD19-positive malignancies, multiple obstacles have so far limited the benefit of CAR T cell therapy for patients with solid tumors. Novel manufacturing and engineering approaches show great promise to enhance CAR T cell function against solid tumors. However, similar to single agent chemotherapy approaches, CAR T cell monotherapy may be unable to achieve high cure rates for patients with difficult to treat solid tumors. Thus, combinatorial drug plus CAR T cell approaches are likely required to achieve widespread clinical success., Methods: We developed a novel, confocal microscopy based, high-content screen to evaluate 1114 FDA approved drugs for the potential to increase expression of the solid tumor antigen B7-H3 on the surface of osteosarcoma cells. Western blot, RT-qPCR, siRNA knockdown and flow cytometry assays were used to validate screening results and identify mechanisms of drug-induced B7-H3 upregulation. Cytokine and cytotoxicity assays were used to determine if drug pre-treatment enhanced B7-H3-CAR T cell effector function., Results: Fifty-five drugs were identified to increase B7-H3 expression on the surface of LM7 osteosarcoma cells using a novel high-content, high-throughput screen. One drug, ingenol-3-angelate (I3A), increased B7-H3 expression by up to 100%, and was evaluated in downstream experiments. Validation assays confirmed I3A increased B7-H3 expression in a biphasic dose response and cell dependent fashion. Mechanistic studies demonstrated that I3A increased B7-H3 (CD276) mRNA, total protein, and cell surface expression via protein kinase C alpha activation. Functionally, I3A induced B7-H3 expression enhanced B7-H3-CAR T cell function in cytokine production and cytotoxicity assays., Conclusions: This study demonstrates a novel high-content and high-throughput screen can identify drugs to enhance CAR T cell activity. This and other high-content technologies will pave the way to develop clinical trials implementing rational drug plus CAR T cell combinatorial therapies. Importantly, the technique could also be repurposed for an array of basic and translational research applications where drugs are needed to modulate cell surface protein expression., (© 2024. The Author(s).)

Background: Australia has one of the highest incidences of colorectal cancer (CRC) worldwide. The Australian National Bowel Cancer Screening Program (NBCSP) is a best-practice, organised screening programme, but uptake is low (40.9%) and increasing participation could reduce morbidity and mortality associated with CRC. Endorsement by GPs is strongly associated with increasing screening uptake., Aim: This study (SMARTscreen) aimed to test whether a multi-intervention short message service (SMS) sent by general practices to 50-60-year-old patients who were due to receive the NBCSP kit would increase NBCSP uptake, by comparing it with usual care., Design and Setting: A stratified cluster randomised controlled trial was undertaken, involving 21 Australian general practices in Western Victoria, Australia., Method: For intervention practices, people due to receive the NBCSP kit within a 6-month study period were sent an SMS just before receiving the kit. The SMS included a personalised message from the person's general practice endorsing the kit, a motivational narrative video, an instructional video, and a link to more information. Control practices continued with usual care, comprising at-home testing with a faecal immunochemical test (FIT) through the NBCSP. The primary outcome was the between-arm percentage difference in uptake of FIT screening within 12 months from randomisation, which was estimated using generalised linear model regression., Results: In total, 39.2% (1143/2914) of people in 11 intervention practices and 23.0% (583/2537) of people in 10 control practices had a FIT result in their electronic health records - a difference of 16.5% (95% confidence interval = 2.02 to 30.9)., Conclusion: The SMS intervention increased NBCSP kit return in 50-60-year-old patients in general practice. This finding informed a larger trial - SMARTERscreen - to test this intervention in a broader Australian population., (© The Authors.)

Background: Time-sensitive emergencies in areas of low population density have statistically poorer outcomes. This includes incidents of major trauma. This study assesses the effect that population density at a receiving hospital of a major trauma patient has on survival., Methods: Patients meeting Trauma Audit Research Network criteria for major trauma from 2016 to 2020 in Ireland were included in this retrospective observational study. Incident data were retrieved from the Major Trauma Audit, while data on population density were calculated from Irish state sources. The primary outcome measure of survival to discharge was compared to population density using logistic regression, adjusted for demographic and incident variables. Records were divided into population density tertiles to assess for between-group differences in potential predictor variables., Results: Population density at a receiving hospital had no impact on mortality in Irish major trauma patients from our logistic regression model (OR = 1.01, 95% CI 0.98-1.05, p = 0.53). Factors that did have an impact were age, Charlson Comorbidity Index, Injury Severity Score, and the presence of an Orthopaedic Surgery service at the receiving hospital (all p < 0.001). Age and Charlson Comorbidity Index differed slightly by population density tertile; both were higher in areas of high population density (all p < 0.001)., Conclusions: Survival to discharge in Irish major trauma patients does not differ substantially based on population density. This is an important finding as Ireland moves to a new trauma system, with features based on population distribution. An Orthopaedic Surgery service is an important feature of a major trauma receiving hospital and its presence improves outcomes., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Person-centred goal planning is increasingly being incorporated into healthcare interventions. People experiencing severe and persistent mental illnesses (SPMIs) have high levels of co-occurring health conditions, reducing their life expectancy when compared with the general population. As medications are commonly used in the treatment of SPMIs, community pharmacists are well-placed to support the health and wellbeing of this population., Objectives: To examine pharmacists' and service users' experiences of goal planning as a component of a community pharmacy-based health intervention for people experiencing SPMIs (PharMIbridge intervention)., Methods: This study utilised a qualitative exploratory approach with an interpretive description method. Semistructured interviews were undertaken with community pharmacists (n = 16) and service user participants (n = 26) who had participated in pharmacist support services for people experiencing SPMIs (PharMIbridge intervention)., Results: Four themes relating to goal planning were identified. First, goal planning provided purpose and motivation for participation in the intervention. Planning realistic goals was important but often challenging. Both pharmacists and service users highlighted the relational aspects of goal planning and how strong relationships supported positive behaviour change and outcomes. Finally, individualised and flexible approaches were important aspects of the intervention, ensuring goals were meaningful to service users., Conclusions: The findings from this study identified positive outcomes from the inclusion of goal-planning processes in a community pharmacy-based health intervention. Further research regarding tools, strategies or training that could support future goal-planning interventions in primary healthcare is needed., Patient or Public Contribution: The PharMIbridge randomised controlled trial research team included lived experience members and was overseen by an expert panel that included members with a lived experience of mental illness and representatives from key organisations. The training provided to pharmacists was co-designed and co-delivered by the researchers and lived experience representatives, and pharmacists were supported by lived experience mentors. Service user participants were invited to participate in the interviews through a number of pathways (e.g., at the completion of the intervention, flyers). Those interested were provided with the full study participant information and provided with a $30 gift voucher at the conclusion of the interview., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy., Methods: We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6 and 12 months of age in infants at typical (N = 92) or elevated likelihood for ASD (N = 90), determined by the presence of an older sibling with ASD. We computed the functional connectivity between cortical sources of EEG during video watching using the corrected imaginary part of phase-locking values., Results: Our main analysis found no significant association between functional connectivity and ASD, showing only significant effects for age, sex, age-sex interaction, and site. Given these null results, we performed an exploratory analysis and observed, at 12 months, a negative correlation between functional connectivity and ADOS calibrated severity scores for restrictive and repetitive behaviors (RRB)., Limitations: The small sample of ASD participants inherent to sibling studies limits diagnostic group comparisons. Also, results from our secondary exploratory analysis should be considered only as potential relationships to further explore, given their increased vulnerability to false positives., Conclusions: These results are inconclusive concerning an association between EEG functional connectivity and ASD in infancy. Exploratory analyses provided preliminary support for a relationship between RRB and functional connectivity specifically, but these preliminary observations need corroboration on larger samples., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: People living with severe and persistent mental illnesses are more likely to experience co-morbid health conditions. Health-related behavior change can be promoted by the use of goal planning within community pharmacy settings., Objectives: To trial and refine a recently developed taxonomy to categorize goals co-designed between community pharmacists and people living with severe and persistent mental illnesses. This study also compared the data to the previously published taxonomy data to determine if the taxonomy could be applied across a range of mental health conditions., Methods: The published goal taxonomy was refined using data from a cluster randomized controlled trial (PharMIbridge). Community pharmacists provided an individualized support service using goal planning with people living with severe and persistent mental illnesses. Goals were categorized using the existing taxonomy and inconsistencies were used to modify and refine the taxonomy. Additionally, participant characteristics and categorization of goals were compared with results from the previous study., Results: 512 goals were reported by 158 consumer participants and categorized into five domains that included a diverse range of health behaviors (e.g., relationships, diet). Minor refinements to the taxonomy were made by replacing, adding or removing categories/descriptors., Conclusions: Significant overlap between the goals of participants and the existing taxonomy was found, supporting the application of the taxonomy across different mental health conditions., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a "healthier profile" and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest.

The long-term sustainability of the African Great Lakes is strongly connected to the management and monitoring of their coastal areas. Yet, the communities that live in these areas are rarely involved in monitoring and have limited influence on key management issues. Furthermore, regulatory activities and knowledge sharing in these transnational ecosystems are strongly limited by funding and infrastructure limitations. Citizen science has great potential to advance both scientific and public understanding of the state of the environment. However, there remains a limited understanding of participants' motivations and expectations, especially in developing countries, where citizen science has great potential to complement regulatory monitoring. The present study explores the motivations of citizen scientists in villages along Lake Tanganyika's northern coast and their potential to take a more active role in lake management. Motivations were examined through qualitative interviews, focus groups, and quantitative surveys with 110 citizen scientists and 110 non-citizen scientists from participating villages. Key motivational factors identified were the desire to contribute to scientific research and local knowledge, as well as aspects of financial compensation. The results confirm that participation in citizen science provides many benefits to participants beyond their role as data aggregators and final knowledge users. However, the incentives to participation varied to those typically considered in citizen science programs conducted in developed countries. To create sustainable long-term community based environmental monitoring, these motivations should be incorporated in the program design and participant recruitment., (© 2023. The Author(s).)

In recent years, there has been a rise in the prevalence of autism spectrum disorder (ASD). The diagnosis of ASD requires behavioral observation and standardized testing completed by highly trained experts. Early intervention for ASD can begin as early as 1-2 years of age, but ASD diagnoses are not typically made until ages 2-5 years, thus delaying the start of intervention. There is an urgent need for non-invasive biomarkers to detect ASD in infancy. While previous research using physiological recordings has focused on brain-based biomarkers of ASD, this study investigated the potential of electrocardiogram (ECG) recordings as an ASD biomarker in 3-6-month-old infants. We recorded the heart activity of infants at typical and elevated familial likelihood for ASD during naturalistic interactions with objects and caregivers. After obtaining the ECG signals, features such as heart rate variability (HRV) and sympathetic and parasympathetic activities were extracted. Then we evaluated the effectiveness of multiple machine learning classifiers for classifying ASD likelihood. Our findings support our hypothesis that infant ECG signals contain important information about ASD familial likelihood. Amongthe various machine learning algorithms tested, KNN performed best according to sensitivity (0.70 ± 0.117), F1-score (0.689 ± 0.124), precision (0.717 ± 0.128), accuracy (0.70 ± 0.117, p -value = 0.02), and ROC (0.686 ± 0.122, p -value = 0.06). These results suggest that ECG signals contain relevant information about the likelihood of an infant developing ASD. Future studies should consider the potential of information contained in ECG, and other indices of autonomic control, for the development of biomarkers of ASD in infancy.

Understanding the neural processes underpinning individual differences in early language development is of increasing interest, as it is known to vary in typical development and to be quite heterogeneous in neurodevelopmental conditions. However, few studies to date have tested whether early brain measures are indicative of the developmental trajectory of language, as opposed to language outcomes at specific ages. We combined recordings from two longitudinal studies, including typically developing infants without a family history of autism, and infants with increased likelihood of developing autism (infant-siblings) (N = 191). Electroencephalograms (EEG) were recorded at 6 months, and behavioral assessments at 6, 12, 18, 24 and 36 months of age. Using a growth curve model, we tested whether absolute EEG spectral power at 6 months was associated with concurrent language abilities, and developmental change in language between 6 and 36 months. We found evidence of an association between 6-month alpha-band power and concurrent, but not developmental change in, expressive language ability in both infant-siblings and control infants. The observed association between 6-month alpha-band power and 6-month expressive language was not moderated by group status, suggesting some continuity in neural mechanisms., (© 2023 The Authors. Infancy published by Wiley Periodicals LLC on behalf of International Congress of Infant Studies.)

Objective: To determine the SARS-CoV-2 seroprevalence among school workers within the Greater Vancouver area, British Columbia, Canada, after the first Omicron wave., Design: Cross-sectional study by online questionnaire, with blood serology testing., Setting: Three main school districts (Vancouver, Richmond and Delta) in the Vancouver metropolitan area., Participants: Active school staff enrolled from January to April 2022, with serology testing between 27 January and 8 April 2022. Seroprevalence estimates were compared with data obtained from Canadian blood donors weighted over the same sampling period, age, sex and postal code distribution., Primary and Secondary Outcomes: SARS-CoV-2 nucleocapsid antibody testing results adjusted for test sensitivity and specificity, and regional variation across school districts using Bayesian models., Results: Of 1850 school staff enrolled, 65.8% (1214/1845) reported close contact with a COVID-19 case outside the household. Of those close contacts, 51.5% (625/1214) were a student and 54.9% (666/1214) were a coworker. Cumulative incidence of COVID-19 positive testing by self-reported nucleic acid or rapid antigen testing since the beginning of the pandemic was 15.8% (291/1845). In a representative sample of 1620 school staff who completed serology testing (87.6%), the adjusted seroprevalence was 26.5% (95% CrI 23.9% to 29.3%), compared with 32.4% (95% CrI 30.6% to 34.5%) among 7164 blood donors., Conclusion: Despite frequent COVID-19 exposures reported, SARS-CoV-2 seroprevalence among school staff in this setting remained no greater than the community reference group. Results are consistent with the premise that many infections were acquired outside the school setting, even with Omicron., Competing Interests: Competing interests: CO'R is an employee of the Vancouver School District, but the latter was not involved in the design, analysis, interpretation of data or the drafting of this manuscript. LifeLabs played no role in the study other than providing a service for the collection of blood samples., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Modeling is essential to better understand the generative mechanisms responsible for experimental observations gathered from complex systems. In this work, we are using such an approach to analyze the electrocardiogram (ECG). We present a systematic framework to decompose ECG signals into sums of overlapping lognormal components. We use reinforcement learning to train a deep neural network to estimate the modeling parameters from an ECG recorded in babies from 1 to 24 months of age. We demonstrate this model-driven approach by showing how the extracted parameters vary with age. From the 751,510 PQRST complexes modeled, 82.7% provided a signal-to-noise ratio that was sufficient for further analysis (>5 dB). After correction for multiple tests, 10 of the 24 modeling parameters exhibited statistical significance below the 0.01 threshold, with absolute Kendall rank correlation coefficients in the [0.27, 0.51] range. These results confirm that this model-driven approach can capture sensitive ECG parameters. Due to its physiological interpretability, this approach can provide a window into latent variables which are important for understanding the heart-beating process and its control by the autonomous nervous system.

Nisin is a broad spectrum bacteriocin used extensively as a food preservative that was identified in Lactococcus lactis nearly a century ago. We show that orally-ingested nisin survives transit through the porcine gastrointestinal tract intact (as evidenced by activity and molecular weight determination) where it impacts both the composition and functioning of the microbiota. Specifically, nisin treatment caused a reversible decrease in Gram positive bacteria, resulting in a reshaping of the Firmicutes and a corresponding relative increase in Gram negative Proteobacteria. These changes were mirrored by the modification in relative abundance of pathways involved in acetate, butyrate (decreased) and propionate (increased) synthesis which correlated with overall reductions in short chain fatty acid levels in stool. These reversible changes that occur as a result of nisin ingestion demonstrate the potential of bacteriocins like nisin to shape mammalian microbiomes and impact on the functionality of the community., (© 2023. The Author(s).)

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Mental Health First Aid (MHFA) training teaches participants how to respond to mental health crises, including suicide. Little is known about the impact of training on participants' observed MHFA behaviours. This exploratory study aimed to compare MHFA-trained Australian and US student pharmacists' performance and suicide assessment language during simulated patient role-play (SPRP) assessments., Methods: Student pharmacists (n = 265) completed MHFA training and participated (n = 81) in SPRPs with simulated patients (SP) who were people with lived experience of mental illness. Each SPRP was marked by three raters (student, tutor and SP). One-way ANOVA, chi-squared tests and independent samples t-tests were used to compare scores and pass/fail rates, where appropriate. Transcribed audio-recordings of suicide assessments underwent discourse analysis. A chi-squared test was conducted to investigate the differences in how suicide assessment language was coded across six discursive frames ('confident'/'timid', 'empathetic'/'apathetic', and 'direct'/'indirect')., Results: Three raters assessed 81 SPRPs, resulting in quantitative analysis of 243 rubrics. There were no significant differences between student pharmacists' mean scores and pass/fail rates across countries. Overall, both cohorts across Australia and the US performed better during the mania scenario, with a low failure rate of 13.9 and 19.0%, respectively. Most students in both countries passed their SPRP assessment; however, 27.8% did not assess for suicide or used indirect language during suicide assessment, despite completing MHFA training. Australian student pharmacists demonstrated, more direct language (76.9% versus 67.9%) and empathy (42.3% versus 32.1%) but less confidence (57.7% versus 60.7%) compared to US student pharmacists, during their suicide assessment; however, these differences were not statistically significant., Conclusions: Findings indicate most MHFA-trained student pharmacists from Australia and the US can provide MHFA during SPRPs, as well as assess for suicide directly, empathetically and confidently. This exploratory study demonstrates the importance of practicing skills post-training and the need for further research exploring participants' hesitance to assess for suicide, despite training completion., (© 2022. The Author(s).)

Introduction: Routine outpatient follow-up visits for surgical patients are a source of strain on health-care resources and patients. With the COVID-19 pandemic adding a new urgency to finding the safest follow-up arrangement, text message follow-up might prove an acceptable alternative to a phone call or an in-person clinic visit., Methods: An open-label, three-arm, parallel randomized trial was conducted. The interventions were traditional in-person appointment, a telephone call, or a text message. The primary outcome was the number of postdischarge complications identified. The secondary outcomes were patient satisfaction with follow-up, future preference, default to follow-up, and preference to receiving medical information by text message., Results: Two hundred eight patients underwent randomization: 50 in the in-person group, 80 in the telephone group, and 78 in the text message group. There was no difference in the number of reported complications: 5 (10%) patients in the in-person group, 7 (9%) patients in the text group, and 11 (14%) patients in the telephone group (P = 0.613). The preferred method of follow-up was by telephone (106, 61.6%). The least preferred was the in-person follow-up (15, 8.7%, P = 0.002), which also had the highest default rate (44%)., Conclusions: There was no evidence that text messages and telephone calls are unsafe and ineffective methods of follow-up. Although most patients are happy to receive results by text message, the majority of patients would prefer a telephone follow-up and are less likely to default by this method. Health-care systems should develop telehealth initiatives when planning health-care services in the wake of the COVID-19 pandemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Computer mediated communication has marked differences from the face-to-face context. One major difference is that, in the online context, we often have explicit access to others' opinions and these opinions are often the only informational cues available. We investigate if awareness of opinion congruence, in the absence of any other reference categories, may be sufficient to foster social identification. In a pre-registered experiment (N = 681), we manipulated exposure to opinions, and measured levels of ingroup identification, opinion-based identification and their social influence on activism intentions. Our results demonstrate exposure to others' opinions in an otherwise anonymous context fosters ingroup and opinion-based identification. There was no effect on opinion-based group activism intentions. We conclude that computer mediated contexts have consequences for identification - opinion (in)congruence is becoming more relevant as a source of social categorization. While we did not find this identification had a social influence on activism, we discuss avenues for future research to disentangle the features of opinion-based groups necessary to foster activism., Competing Interests: Declaration of competing interest We have no conflict of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

We prospectively studied SARS-CoV-2 transmission at schools in an era of variants of concern, offering all close contacts serial viral asymptomatic testing up to 14 days. From the 69 primary cases detected in schools, 392 close contacts were identified and offered asymptomatic testing. A total of 229 (58%) were close school contacts, and of these, 3 tested positive (1.3%), 2 of which were detected through asymptomatic testing. This is in contrast to the 117 household contacts, where 43 (37%) went on to become secondary cases. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission. IMPORTANCE There is concern that schools may be a setting where asymptomatic infections might result in significant "silent" transmission of SARS-CoV-2, particularly after the emergence of more transmissible variants of concern. After the programmatic implementation of a strategy of asymptomatic testing of close COVID-19 contacts as part of contact tracing in the school setting, the majority of the secondary cases were still found to have occurred in home or social contacts. However, for the 6.2% of secondary cases that occurred in close school contacts, the majority were detected through asymptomatic testing. The potential added yield of this approach needs to be considered within the overall setting, including consideration of the local epidemiology, ongoing goals of case and contact management, additional costs, logistical challenges for families, and possible health impacts of asymptomatic transmission.

Several studies in Lake Tanganyika have effectively employed traditional methods to explore changes in water quality in open waters; however, coastal monitoring has been restricted and sporadic, relying on costly sample and analytical methods that require skilled technical staff. This study aims in validating citizen science water quality collected data (nitrate, phosphate and turbidity) with those collected and measured by professional scientists in the laboratory. A second objective of the study is to use citizen scientist data to identify the patterns of seasonal and spatial variations in nutrient conditions and forecast potential changes based on expected changes in population and climate (to 2050). The results showed that the concentrations of nitrate and phosphate measured by citizen scientists nearly matched those established by professional scientists, with overall accuracy of 91% and 74%, respectively. For total suspended solids measured by professional and turbidity measured by citizen scientists, results show that, using 14 NTU as a cut-off, citizen scientist measurements of Secchi tube depth to identify lake TSS below 7.0 mg/L showed an accuracy of 88%. In both laboratory and citizen scientist-based studies, all measured water quality variables were significantly higher during the wet season compared to the dry season. Climate factors were discovered to have a major impact on the likelihood of exceeding water quality restrictions in the next decades (2050), which could deteriorate lake conditions. Upscaling citizen science to more communities on the lake and other African Great Lakes would raise environmental awareness, inform management and mitigation activities, and aid long-term decision-making., (© 2022. The Author(s).)

The orexigenic hormone ghrelin has multifaceted roles in health and disease. We have reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), protects against metabolic dysfunction of adipose tissues in aging. Our further observation interestingly revealed that GHS-R deficiency phenocopies the effects of myokine irisin. In this study, we aim to determine whether GHS-R affects the metabolic functions of aging skeletal muscle and whether GHS-R regulates the muscular functions via irisin. We first studied the expression of metabolic signature genes in gastrocnemius muscle of young, middle-aged and old mice. Then, old GHS-R knockout ( Ghsr -/- ) mice and their wild type counterparts were used to assess the impact of GHS-R ablation on the metabolic characteristics of gastrocnemius and soleus muscle. There was an increase of GHS-R expression in skeletal muscle during aging, inversely correlated with the decline of metabolic functions. Remarkedly the muscle of old GHS-R knockout ( Ghsr -/- ) mice exhibited a youthful metabolic profile and better maintenance of oxidative type 2 muscle fibers. Furthermore, old Ghsr -/- mice showed improved treadmill performance, supporting better functionality. Also intriguing to note was the fact that old GHS-R-ablated mice showed increased expression of the irisin precursor FNDC5 in the muscle and elevated plasma irisin levels in circulation, which supports a potential interrelationship between GHS-R and irisin. Overall, our work suggests that GHS-R has deleterious effects on the metabolism of aging muscle, which may be at least partially mediated by myokine irisin.

Objectives: Few studies reported COVID-19 cases in schools during the 2020/21 academic year in a setting of uninterrupted in-person schooling. The main objective was to determine the SARS-CoV-2 seroprevalence among school staff in Vancouver public schools., Design: Cumulative incident COVID-19 cases among all students and school staff based on public health data, with an embedded cross-sectional serosurvey among a school staff sample that was compared to period, age, sex and geographical location-weighted data from blood donors., Setting: Vancouver School District (British Columbia, Canada) from kindergarten to grade 12., Participants: Active school staff enrolled from 3 February to 23 April 2021 with serology testing from 10 February to 15 May 2021., Main Outcome Measures: SARS-CoV-2 seroprevalence among school staff, based on spike (S)-based (unvaccinated staff) or N-based serology testing (vaccinated staff)., Results: Public health data showed the cumulative incidence of COVID-19 among students attending in-person was 9.8 per 1000 students (n=47 280), and 13 per 1000 among school staff (n=7071). In a representative sample of 1689 school staff, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week (IQR: 5.0-25 hours). Although 21.5% (363/1686) of surveyed staff self-reported close contact with a COVID-19 case outside of their household (16.5% contacts were school-based), 5 cases likely acquired the infection at school based on viral testing. Sensitivity/Specificity-adjusted seroprevalence in 1556/1689 staff (92.1%) was 2.3% (95% CI: 1.6% to 3.2%), comparable to a sex, age, date and residency area-weighted seroprevalence of 2.6% (95% CI: 2.2% to 3.1%) among 5417 blood donors., Conclusion: Seroprevalence among staff was comparable to a reference group of blood donors from the same community. These data show that in-person schooling could be safely maintained during the 2020/21 school year with mitigation measures, in a large school district in Vancouver, Canada., Competing Interests: Competing interests: CO'R is an employee of the Vancouver School District, but the District was not involved in the design, analysis, interpretation of the data or the drafting of this manuscript; MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments; the authors declare no relevant conflicts of interest. LifeLabs and Dynacare played no role in the study other than providing a service for the collection of blood samples., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is substantial evidence of age-related declines in anatomical connectivity during adulthood, with associated alterations in functional connectivity. But the relation of those functional alterations to the structural reductions is unclear. The complexities of both the structural and the functional connectomes make it difficult to determine such relationships. We pursue this question with methods, based on animal research, that specifically target the interhemispheric connections between the visual cortices. We collect t1- and diffusion-weighted imaging data from which we assess the integrity of the white matter interconnecting the bilateral visual cortices. Functional connectivity between the visual cortices is measured with electroencephalography during the presentation of drifting sinusoidal gratings that agree or conflict across hemifields. Our results show age-related reductions in the integrity of the white matter interconnecting the visual cortices, and age-related increases in the difference in functional interhemispheric lagged coherence between agreeing versus disagreeing visual stimuli. We show that integrity of the white matter in the splenium of the corpus callosum predicts the differences in lagged coherence for the agreeing versus disagreeing stimuli; and that this relationship is mediated by age. These results give new insight into the causal relationship between age and functional connectivity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The ability to predict formulation behaviour at production scale during formulation design can reduce the time to market and decrease product development costs. However, it is challenging to extrapolate compaction settings for direct compression formulations between tablet press models during scale-up and transfer from R&D to commercial production. The aim of this study was to develop statistical process models to predict tablet tensile strength, porosity and disintegration time from compaction parameters (pre-compression and main compression force, and press speed), for three formulations, with differing deformation characteristics (plastic, brittle and elastic), on three tablet press models (one pilot-scale tablet press (KG RoTab) and two production-scale presses (Fette 1200i and GEA Modul P)). The deformation characteristics of yield pressure and elastic recovery were determined for the model placebo formulations investigated. To facilitate comparison of dwell time settings between tablet press models, the design of experiments (DoE) approach was 9 individual 16-run response surface DoEs (3 formulation × 3 press models), whose results were combined to create a polynomial regression model for each tablet property. These models predicted tablet tensile strength, porosity and disintegration time and enabled the construction of design spaces to produce tablets with specified target properties, for each formulation on each press. The models were successfully validated. This modelling approach provides an understanding of the compaction behaviour of formulations with varying deformation behaviour on development and commercial tablet press models. This understanding can be applied to inform achievable production rates at a commercial scale, during the formulation development.

Aims: Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota., Methods and Results: Faecal slurries were prepared from fresh faecal samples and spiked with C. difficile (10 6  CFU per ml). Nisin was added to each fermentation at a range of concentrations from 0 to 500 µM. Following 24 h, 16S rRNA gene sequencing was performed, and the presence of viable C. difficile was assessed. There was no viable C. difficile detected in the presence of 50-500 µM nisin. There was a decrease in the diversity of the microbiota in a nisin dose-dependent manner. Nisin predominantly depleted the relative abundance of the Gram-positive bacteria whilst the relative abundance of Gram-negative bacteria such as Escherichia Shigella and Bacteroides increased., Conclusions: Using an ex vivo model of the colon, this study demonstrates the ability of purified nisin to selectively deplete C. difficile in a faecal microbial environment and establishes the minimum concentration at which this occurs whilst having a minimal impact on the composition of the microbiota., Significance and Impact of the Study: This study opens up the potential to use nisin as a therapeutic for clostridial gut infections., (© 2021 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Background: Increasing participation in the Australian National Bowel Cancer Screening Program (NBCSP) is the most efficient and cost-effective way of reducing mortality associated with colorectal cancer by detecting and treating early-stage disease. Currently, only 44% of Australians aged 50-74 years complete the NBCSP. This efficacy trial aims to test whether this SMS intervention is an effective method for increasing participation in the NBCSP. Furthermore, a process evaluation will explore the barriers and facilitators to sending the SMS from general practice., Methods: We will recruit 20 general practices in the western region of Victoria, Australia to participate in a cluster randomised controlled trial. General practices will be randomly allocated with a 1:1 ratio to either a control or intervention group. Established general practice software will be used to identify patients aged 50 to 60 years old who are due to receive a NBCSP kit in the next month. The SMS intervention includes GP endorsement and links to narrative messages about the benefits of and instructions on how to complete the NBCSP kit. It will be sent from intervention general practices to eligible patients prior to receiving the NBCSP kit. We require 1400 eligible patients to provide 80% power with a two-sided 5% significance level to detect a 10% increase in CRC screening participation in the intervention group compared to the control group. Our primary outcome is the difference in the proportion of eligible patients who completed a faecal occult blood test (FOBT) between the intervention and control group for up to 12 months after the SMS was sent, as recorded in their electronic medical record (EMR). A process evaluation using interview data collected from general practice staff (GP, practice managers, nurses) and patients will explore the feasibility and acceptability of sending and receiving a SMS to prompt completing a NBCSP kit., Discussion: This efficacy trial will provide initial trial evidence of the utility of an SMS narrative intervention to increase participation in the NBCSP. The results will inform decisions about the need for and design of a larger, multi-state trial of this SMS intervention to determine its cost-effectiveness and future implementation., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12620001020976 . Registered on 17 October 2020., (© 2022. The Author(s).)