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Introduction Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings.Methods and analysis We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives.Ethics and dissemination This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals.Trial registration number NCT06455384.

Background and objectives: Food-to-food fortification (FtFF) is gaining traction as a strategy to enhance nutritional value of cereal-based foods. Sorghum, a major food crop for millions in the semi-arid tropics lends itself to such FtFF efforts. Such food-to-food fortified (FtF fortified) foods also contain bioactive phenolics with health-promoting properties in relation to potential protection against diet-related non-communicable diseases (NCDs) whose prevalence is increasing in sub-Saharan Africa. In this study, the effects of extrusion cooking of sorghum-based porridges FtF fortified with baobab fruit powder and moringa leaf powder on antioxidant, anti-inflammatory, antidiabetic and anti-lipogenic properties were determined. Findings: FtFF porridges showed higher phenolic content (phenolic acids and their esters, flavonoids and their glycosides) and greater radical scavenging properties and reduction in advanced glycation end products (AGEs) compared to unfortified porridges. Extruded instant porridges had lower phenolic content, radical scavenging properties and showed less reduction in AGEs compared to conventionally wet-cooked porridges. All porridges exerted antioxidant effects in Caco-2 cells and FtFF inhibited nitric oxide (NO) formation in RAW 264.7 cells. Extracts from all porridge samples exhibited prevention and reduction of adipocyte formation in 3 T3-L1 cells, indicating anti-lipogenic effects. Conclusion: FtFF (with moringa and baobab) and extrusion cooking can be used to produce instant porridges from wholegrain sorghums with targeted health-promoting properties to address rising non-communicable diseases in sub-Saharan Africa. Significance and novelty: This study highlights the potential of FtFF with tropical plant foodstuffs to improve health-promoting properties of cereal wholegrain-based starchy staple foods.

Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of Protorhus longifolia (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPARγ, SREBP-1, and AMPK, with lower binding affinity to C/EBPα, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with Ki and IC50 values ranging from 28.7 to 52.9 μM and 27.6 to 35.8 μM, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid–induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 μM) was comparable to 50 μM lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPARγ, C/EBPα, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 μM was similar to 50 μM lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.

Sulfur oxides that originate from fuels can cause compounding damage to the environment if left unchecked. As such, deeper desulfurization methods have been researched for higher sulfur conversion for cleaner fuels. Oxidative desulfurization (ODS) is a promising substitute for hydrodesulfurization as it focuses on organosulfur compounds and has lower reaction conditions. Improving the conversion percent involves several parameters, such as reaction temperature, oxidant concentration, catalyst dosage, and catalyst nature. One of the most efficient catalysts for ODS is polyoxometalates. They are homogeneous catalysts with transition metal centers. This makes it difficult to extract from the fuel to reuse in another ODS cycle. This paper reviews the available supports for polyoxometalate catalysts which help increase recyclability and conversion efficiency. Supports create heterogeneous catalysts that are easier to extract after ODS. These include metal oxides, activated carbon, silica, and metal-organic frameworks (MOF). Metal oxides tend to be the most stable due to strong intermolecular bonds between the polyoxometalate and the metal. They can also be customized depending on the catalyst requirements. Activated carbon and silica are incredibly porous which are desirable qualities for a heterogeneous catalyst. It allows for more sulfur to adhere to the surface of the catalyst which increases the conversion percentage. MOFs have the benefit of being porous while also having adsorptive desulfurization capabilities. Increasing recyclability can increase the volume of desulfurized fuel while reducing costs.

Streptozotocin (STZ) is a commonly used compound for the induction of type 2 diabetes (T2D) in animal models, but its effects on non-pancreatic tissues like the lungs are not well understood. This study aimed to examine the histopathological impact of STZ on the lungs using male Sprague-Dawley rats. The rats were divided into two groups: a control group on a normal diet and an STZ-treated group receiving a high-fat diet and 10% sucrose water for 8 weeks, followed by an STZ injection (30 mg/kg body weight). All rats were terminated 9 days after STZ administration, and lung samples were collected for light microscopy, transmission electron microscopy (TEM), and confocal laser scanning microscopy. Light microscopy revealed thickening of alveolar septa, narrowing of alveoli, and inflammatory infiltrates in the STZ group. TEM showed mitochondrial damage in type 2 pneumocytes, including membrane fragmentation, cristae loss, and formation of mitochondrial-derived vesicles. Confocal microscopy revealed significantly higher expression of myeloperoxidase, neutrophil elastase, and citrullinated histone 3 in the STZ group compared to controls. These findings suggest that STZ induces considerable lung damage, emphasizing the need to consider lung toxicity in studies involving STZ. [ABSTRACT FROM AUTHOR]

Triterpenoids have been identified as potential novel lipid‐lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM‐2 and RA‐5) isolated from the stem bark of Protorhus longifolia (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPARγ, SREBP‐1, and AMPK, with lower binding affinity to C/EBPα, pancreatic lipase, and hormone‐sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with Ki and IC50 values ranging from 28.7 to 52.9 μM and 27.6 to 35.8 μM, respectively. Total and neutral lipid accumulation in differentiated 3T3‐L1 adipocytes and the oleic acid–induced HepG2 cell model was inhibited, with ARM‐2 showing better inhibition than RA‐5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 μM) was comparable to 50 μM lovastatin, although the latter was cytotoxic, whereas both ARM‐2 and RA‐2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP‐1, PPARγ, C/EBPα, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM‐2 and RA‐5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 μM was similar to 50 μM lovastatin and simvastatin. This study identifies that the triterpenoids, ARM‐2 and RA‐5, have the potential to modulate lipogenesis and lipolysis. [ABSTRACT FROM AUTHOR]

Objective: This study uses in‐depth interviews and ecomapping techniques to explore LGBTQ youths' relationships with child welfare professionals and other affiliated, nonparental adults (CWP/ANPAs) who play a primary role in providing them with care and services. Background: Supportive relationships with caring adults are essential in reducing minority stress impacts and improving outcomes for LGBTQ foster youth, who often face victimization affecting their access to support. However, limited knowledge exists regarding LGBTQ foster youths' relationships with CWP/ANPAs and the role of relational support in their identity disclosure and access to appropriate care and services. Method: Twenty‐one LGBTQ foster youth, aged 17 to 21, participated in interviews and constructed visual diagrams of their relationships with CWP/ANPAs. Data were analyzed using directed content analysis. Results: Findings highlight the need for CWP/ANPAs to improve relationships with LGBTQ foster youth. These improvements can be achieved through engagement in attitudes and practices that facilitate relationship development (e.g., empathy, respect, affirmation, knowledge, responsiveness), and reduce existing barriers (e.g., neglect, discrimination, mistreatment, lack of knowledge, fear of rejection). Conclusions: To provide better support LGBTQ foster youth, CWP/ANPAs and child welfare agencies should increase their knowledge and skills, be more responsive to LGBTQ youths' specific needs, and implement inclusive policies and practice standards. Implications: CWP/ANPAs and agencies working with LGBTQ foster youth must develop an awareness and understanding of the strengths, needs, and challenges of LGBTQ foster youth to reduce stigma, bias, and discrimination in the foster care system and engage in affirming actions and practices that create a more inclusive environment for this population. [ABSTRACT FROM AUTHOR]

Sulfur oxides that originate from fuels can cause compounding damage to the environment if left unchecked. As such, deeper desulfurization methods have been researched for higher sulfur conversion for cleaner fuels. Oxidative desulfurization (ODS) is a promising substitute for hydrodesulfurization as it focuses on organosulfur compounds and has lower reaction conditions. Improving the conversion percent involves several parameters, such as reaction temperature, oxidant concentration, catalyst dosage, and catalyst nature. One of the most efficient catalysts for ODS is polyoxometalates. They are homogeneous catalysts with transition metal centers. This makes it difficult to extract from the fuel to reuse in another ODS cycle. This paper reviews the available supports for polyoxometalate catalysts which help increase recyclability and conversion efficiency. Supports create heterogeneous catalysts that are easier to extract after ODS. These include metal oxides, activated carbon, silica, and metal-organic frameworks (MOF). Metal oxides tend to be the most stable due to strong intermolecular bonds between the polyoxometalate and the metal. They can also be customized depending on the catalyst requirements. Activated carbon and silica are incredibly porous which are desirable qualities for a heterogeneous catalyst. It allows for more sulfur to adhere to the surface of the catalyst which increases the conversion percentage. MOFs have the benefit of being porous while also having adsorptive desulfurization capabilities. Increasing recyclability can increase the volume of desulfurized fuel while reducing costs. [ABSTRACT FROM AUTHOR]

Industrial robots are of great significance to the long-term development of family firms. Drawing on the lens of the principal–principal conflict, this paper aims to investigate the influence of family non-executive directors on robot adoption in Chinese family firms. This paper selects the family firms in China from 2011 to 2019 as the sample. Furthermore, the authors manually collected the family non-executive directors and constructed the robot adoption variable utilizing data sourced from the International Federation of Robotics. In brief, this paper constructs a comprehensive framework of the mechanisms and additional tests pertaining to the influence of family non-executive directors on robot adoption. This paper finds that family non-executive directors can promote robot adoption in family firms. The underlying mechanism analysis shows that family non-executive directors promote robot adoption by exerting financial and human effects. This paper further finds that the characteristics of family non-executive directors, such as kinship, differential shareholding and excessive directors, affect the role of family non-executive directors. Finally, robot adoption can improve future performance, and the promotional effect is more evident when family members are non-executive directors. This paper contributes to the related literature from the following two aspects. Firstly, this paper decomposes the types of family directors to understand the role of family non-executive directors, which challenges the assumption that family board members are homogeneous in family firms. Second, this paper expands the research on the factors that influence robot adoption in emerging economies from the micro-enterprise level. In addition, the findings in this paper have managerial implications for family firms to optimize their strategic decisions with the help of the mode of board right allocation.

Abstract Background Tic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis. Methods We analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts. Results Our findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation. Conclusion These results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis.

BACKGROUND: Temporal bone (TB) fractures are frequently accompanied by intracranial injury. This study aimed to analyze combined intracranial injuries in relation to functional changes in the inner ear, including those of the contralateral ear, in patients with TB fractures. METHODS: Ninety-four patients (mean age: 35.6 ± 18.7 years, M : F=67 : 27) diagnosed with unilateral TB fracture were included. Bone conduction (BC) threshold, word recognition score (WRS), and changes in vestibular function were compared based on intracranial injuries, focusing on the contralateral side. RESULTS: Various types of intracranial injuries were observed (67.9%). Among these, a significant association between traumatic brain injury (TBI) and otic capsule-violating fractures was noted. The BC threshold on the fractured side significantly deteriorated in patients with TBI. Additionally, a significantly worse BC threshold was confirmed on the contralateral side in patients with TBI, intracranial hemorrhage (ICH), and contrecoup injury. The follow-up BC threshold did not improve or differ, regardless of high-dose steroid administration. The initial WRS and canal paresis in the bithermal caloric test were not significantly different in the presence of each intracranial injury. Concurrent fluctuations in the pressure of the cerebrospinal fluid space and perilymphatic space were speculated to be the potential underlying mechanisms. CONCLUSION: A significantly worse BC threshold was confirmed on the contralateral side of patients with TBI, contrecoup injury, ICH, and on fracture sides of patients with TBI.

Abstract Electrochemical hydrogen peroxide (H2O2) production (EHPP) via a two-electron oxygen reduction reaction (2e- ORR) provides a promising alternative to replace the energy-intensive anthraquinone process. M-N-C electrocatalysts, which consist of atomically dispersed transition metals and nitrogen-doped carbon, have demonstrated considerable EHPP efficiency. However, their full potential, particularly regarding the correlation between structural configurations and performances in neutral media, remains underexplored. Herein, a series of ultralow metal-loading M-N-C electrocatalysts are synthesized and investigated for the EHPP process in the neutral electrolyte. CoNCB material with the asymmetric Co-C/N/O configuration exhibits the highest EHPP activity and selectivity among various as-prepared M-N-C electrocatalyst, with an outstanding mass activity (6.1 × 105 A gCo −1 at 0.5 V vs. RHE), and a high practical H2O2 production rate (4.72 mol gcatalyst −1 h−1 cm−2). Compared with the popularly recognized square-planar symmetric Co-N4 configuration, the superiority of asymmetric Co-C/N/O configurations is elucidated by X-ray absorption fine structure spectroscopy analysis and computational studies.

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

AimHearing loss, affecting a significant portion of the global population, is prevented with peroxisome proliferator-activated receptor γ agonism. Understanding potential protective treatments is crucial for public health. We examine the effect of telmisartan, an antihypertensive drug and partial peroxisome proliferator-activated receptor γ agonist, on hearing loss in patients with hypertension.Method and resultsThis retrospective cohort analysis used data from the OMOP Common Data Model database, encompassing information from three tertiary institutions in South Korea. The study included a substantial sample size of 860,103 people diagnosed with hypertension. The study included individuals who had been medically diagnosed with hypertension and had been prescribed antihypertensive drugs, including telmisartan. The study design was established to evaluate the comparative effects of telmisartan and other hypertension medications on hearing loss. We used propensity score matching (PSM) to create a balanced cohort, reducing potential biases between the telmisartan and non-telmisartan groups. From the initial 860,103 patients with hypertension, a propensity score matched cohort was derived from 20,010 patients, with 2,193 in the telmisartan group. After PSM, lower incidence of total hearing loss was observed in the telmisartan group compared to the non-telmisartan group during the 3-year follow-up (0.5% vs. 1.5%, log-rank p = 0.005). In subgroup analysis, this study showed consistent results that lower incidence of total hearing loss was higher in the telmisartan group than in the non-telmisartan group.ConclusionTelmisartan was associated with reducing certain types of hearing loss in patients with hypertension. Further research is needed to confirm these findings and understand the mechanisms.

Abstract Despite increasing exposure to flooding and associated financial damages, estimates suggest more than two‐thirds of flood‐exposed properties are currently uninsured. This low adoption rate could undermine the climate resilience of communities and weaken the financial solvency of the United States National Flood Insurance Program. We study whether repeated exposure to flood events, especially the disaster‐scale floods that are expected to become more frequent in a warming climate, could spur insurance adoption. Using improved estimates of residential insurance take‐up in locations where such insurance is voluntary, and exploiting variation in the frequency and severity of flood events over time, we quantify how flood events impact local insurance demand. We find that a flood disaster declaration in a given year increases the take‐up rate of insurance by 7% in the following year, but that the effect diminishes in subsequent years and is gone after 5 years. This effect is more short‐lived in counties in inland states that do not border the Gulf and Atlantic coasts. We also find that the effect of a flood on take‐up is substantially larger if there was also a flood in the previous year, and that recent disasters are more salient for homeowners whose primary residences are exposed to a disaster declaration compared to non‐primary residences. Overall, these findings suggest that relying on households to self‐adapt to increasing flood risks in a changing climate is insufficient for closing the insurance protection gap.

An examination of sustainable living practices through the lens of ecofeminism is the subject of this article. In this article, sustainable living practices refers to the actual implementation of environmentalism ideas in everyday situation. The selection of this subject is deemed significant due to the prevailing trend in environmental literature to associate it as pro-environmental behaviour that, unlike environmental activism, exclusively with the upper middle class, thereby rendering it feeble, apolitical, and inconsequential. This study aims to evaluate the correlation between pro-environmental behaviour and environmental action and activism by examining sustainable living practices through the lens of gender. Departing from Ecofeminism, it attempts to incorporate insights from relevant literature to enhance the discussion. Availing from exploratory field observations, this study uses Indonesia as a case studies. The study found that, in addition to the availability of social media and spiritual factors, there are educational orientation that, related to cultural and religious aspects, bridges private/public elements as well as agents/victims division in Ecofeminism discourse. The transformation of the movement’s character from individualist to collectivist is influenced by global political dynamics, as well as showing the moral and spiritual orientation of this movement. Keywords: sustainable living practice, ecofeminism, environmental care, pro-environmental behaviour, environmental activism

Abstract Background Some studies have suggested that hepatitis B virus (HBV) infection had a negative association with semen quality, but the conclusions have been inconsistent. The purpose of our study was to systematically assess the association between HBV infection and semen parameters. Methods We searched electronic databases for studies published from January 1980 to August 2023. Eleven studies were included in the analysis. Primary outcomes were semen volume, sperm concentration, sperm morphology, sperm motility and sperm progressive motility. We also conducted a subgroup analysis between China and other countries. Result Compared with the semen quality of HBV-negative men, HBV infection had a negative association with semen volume (MD: −0.20 mL, 95%CI: −0.32 to − 0.09, P = 0.0004), sperm concentration (MD: −4.46 × 106/mL, 95%CI: −7.09 to − 1.84, P = 0.0009), sperm morphology (MD: −2.49%, 95%CI: −4.35 to − 0.64, P = 0.008), sperm motility (MD: −6.85%, 95%CI: −11.53 to − 2.18, P = 0.004), and sperm progressive motility (MD: −6.63%, 95%CI: −10.24 to − 3.02, P = 0.0003). However, HBV infection had no significant association with total sperm count (MD: −31.50 × 106, 95%CI: −74.11 to 11.10, P = 0.15). The association between HBV and semen quality were inconsistent between the subgroups. Conclusion HBV infection had a negative association with sperm concentration, motility, morphology, and semen volume. However, The association between HBV and total sperm count remain unclear. This metaanalysis suggests that we should pay attention to the adverse effect of HBV on sperm quality, and several studies have reported the relevant mechanisms. But due to the significant heterogeneity among studies on some semen parameters, further large and well-designed researches are needed before introducing clinical management recommendations.

Gonadotropin-releasing hormone agonists are uncommonly associated with hypersensitivity reactions. To date, there have been few reports of these cases by allergists and no clear published protocols on testing. Here, we report the case of a patient who had a potential reaction to leuprolide acetate depot and a framework for assessing for drug hypersensitivity with the available literature in mind.

Background: This retrospective, cross-sectional study aimed to assess the functional hearing capacity of individuals with Chronic Otitis Media (COM) using prediction modeling techniques and the Hearing Handicap Inventory for the Elderly (HHIE) questionnaire. This study investigated the potential of predictive models to identify hearing levels in patients with COM. Methods: We comprehensively examined 289 individuals diagnosed with COM, of whom 136 reported tinnitus and 143 did not. This study involved a detailed analysis of various patient characteristics and HHIE questionnaire results. Logistic and Random Forest models were employed and compared based on key performance metrics. Results: The logistic model demonstrated a slightly higher accuracy (73.56%), area under the curve (AUC; 0.73), Kappa value (0.45), and F1 score (0.78) than the Random Forest model. These findings suggest the superior predictive performance of the logistic model in identifying hearing levels in patients with COM. Conclusions: Although the AUC for the logistic regression did not meet the benchmark, this study highlights the potential for enhanced reliability and improved performance metrics using a larger dataset. The integration of prediction modeling techniques and the HHIE questionnaire shows promise for achieving greater diagnostic accuracy and refining intervention strategies for individuals with COM.

This research investigates the joint effect of individual emotional experiences and societal expectations on life satisfaction. Inspired by the Affect Valuation Theory and Self-Discrepancy Theory, we explored how discrepancies between actual emotional experiences and what society believes we “ought” to feel are linked with life satisfaction. A total of 301 U.S. online participants rated their emotional experiences and societal expectations for emotions, along with measures of life satisfaction. Response surface analyses were used to assess the effect of emotional experience-norm congruence on life satisfaction. Findings revealed that the highest life satisfaction reported by individuals infrequently experiencing negative emotions but perceiving high societal expectations for these emotions, while congruence effects were not supported. These findings suggest the potential benefits of a societal shift toward greater acceptance of a wider range of negative emotions. The study may potentially stimulate interventions to enhance individuals' life satisfaction by reconsidering societal beliefs about emotions.

IntroductionThere is no consensus as to what specifically constitutes head and neck cancer radiotherapy quality assurance (HNC RT QA). The aims of this study are to (1) describe the RT QA processes used in the TROG 12.01 study, (2) review the RT QA processes undertaken for all patients with loco-regional failure (LRF), and (3) provide prospective data to propose a consensus statement regarding the minimal components and optimal timing of HNC RT QA.Materials and methodsAll patients undergoing RT QA in the original TROG 12.01 study were included in this substudy. All participating sites completed IMRT credentialling and a clinical benchmark case. Real-time (pre-treatment) RT QA was performed for the first patient of each treating radiation oncologist, and for one in five of subsequent patients. Protocol violations were deemed major if they related to contour and/or dose of gross tumour volume (GTV), high dose planning target volume (PTVhd), or critical organs of risk (spinal cord, mandible, and brachial plexus).ResultsThirty HNROs from 15 institutions accrued 182 patients. There were 28 clinical benchmark cases, 27 pre-treatment RT QA cases, and 38 post-treatment cases. Comprehensive RT QA was performed in 65/182 (36%) treated patients. Major protocol violations were found in 5/28 benchmark cases, 5/27 pre-treatment cases, and 6/38 post-treatment cases. An independent review of all nine LRF cases showed major protocol violations in four of nine cases.ConclusionOnly pre-treatment RT QA can improve patient outcomes. The minimal components of RT QA in HNC are GTVs, PTVhd, and critical organs at risk. What constitutes major dosimetric violations needs to be harmonised.

Background: Accurate prognostic prediction is crucial for managing Idiopathic Sudden Sensorineural Hearing Loss (ISSHL). Previous studies developing ISSHL prognosis models often overlooked individual variability in hearing damage by relying on fixed frequency domains. This study aims to develop models predicting ISSHL prognosis one month after treatment, focusing on patient-specific hearing impairments. Methods: Patient-Personalized Seigel’s Criteria (PPSC) were developed considering patient-specific hearing impairment related to ISSHL criteria. We performed a statistical test to assess the shift in the recovery assessment when applying PPSC. The utilized dataset of 581 patients comprised demographic information, health records, laboratory testing, onset and treatment, and hearing levels. To reduce the model’s reliance on hearing level features, we used only the averages of hearing levels of the impaired frequencies. Then, model development, evaluation, and interpretation proceeded. Results: The chi-square test (p-value: 0.106) indicated that the shift in recovery assessment is not statistically significant. The soft-voting ensemble model was most effective, achieving an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.864 (95% CI: 0.801–0.927), with model interpretation based on the SHapley Additive exPlanations value. Conclusions: With PPSC, providing a hearing assessment comparable to traditional Seigel’s criteria, the developed models successfully predicted ISSHL recovery one month post-treatment by considering patient-specific impairments.

1. Upon completion of this session, participants will be able to describe the ethical challenges in decision-making for patients with life-threatening though potentially survivable injury after attempted suicide. 2. Upon completion of this session, participants will be able to analyze methods for resolving clinical and ethical conflicts related to end-of-life decision making for patients with serious mental illness. Medical decision-making for patients without decision-making capacity who have attempted suicide can present ethical challenges, particularly when a patient has a life-threatening though potentially survivable injury. We present a modified case that highlights the need for interdisciplinary guidelines and best-practices for the care of these patients. Mr. C is a 56-year-old man with history of schizoaffective disorder complicated by previous suicide attempts. He presented to the hospital following a self-inflicted gunshot wound to the head. He was intubated in the field and was found to have significant intracranial bleeding and facial disfigurement. By legal default, his younger brother was his surrogate decision-maker. After emergency stabilization, providers shared that Mr. C had an estimated 50% chance of survival if he were to proceed with a high-risk series of intracranial evacuation and reconstructive plastics procedures, followed by months of high-intensity rehabilitation. Comfort-focused care and compassionate extubation were proposed as the alternative treatment plan. The palliative care, ethics, legal, and psychiatry teams were consulted, with trauma surgery and neurosurgery co-managing. Mr. C's brother desired to transition to comfort-focused care based on his mental health history and prior conversations about goals/values. However, the psychiatry team felt a "legal and ethical obligation" existed to proceed with full treatment given the potential for survival. They felt Mr. C's diagnosis of schizoaffective disorder was not treatment refractory and raised concerns that caregiver burnout may be affecting the brother's decision-making. The surgical teams also supported proceeding with treatment. After further discussion, the hospital legal and ethics teams deemed that Mr. C's brother was acting as an appropriate surrogate. As such, Mr. C was transferred to inpatient hospice, compassionately extubated, and died with his brother at his side. Mr. C's case highlights the challenges of medical decision-making for patients with suicide attempts and life-threatening though potentially survivable injuries. These cases can lead to significant moral distress for medical providers and families. We propose a standard of care that balances surrogate decision-maker experience and knowledge of prior goals of care as well as quality of life considerations with available treatment and prognostic information. Ethical / Legal Aspects of Care; Interdisciplinary Teamwork / Professionalism [ABSTRACT FROM AUTHOR]

Introduction: Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings., Methods and Analysis: We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives., Ethics and Dissemination: This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals., Trial Registration Number: NCT06455384., Competing Interests: Competing interests: YB and MC are cofounders of Genetics Adviser., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.