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Shared Musical Lives: Philosophy, Disability, and the Power of Sonification, by Licia Carlson. New York: Oxford University Press, 2022. x, 118 pp. Licia Carlson is a philosopher of disability and [...]

This article examines the nuance of aging masculinity presented in hard-boiled detective fiction, something that is frequently lost amid sleek Hollywood portrayals of these characters. The detectives of this genre are inevitably middle-aged men and aging—along with vulnerability—is thus a fundamental, if often disavowed, element of the form. Among the early authors of this school, Raymond Chandler proves to be the most reflective on the topic of mortality. This article examines The Long Goodbye (1953) as a guiding illustration of hard-boiled insights into aging, along with supporting examples from the genre’s history, particularly the works of Dashiell Hammett. The question of hard-boiled realism is of special note to this discussion, as these works ostensibly offer a platform for more “true” representations of male bodies as they age. However, Chandler’s hard-boiled realism, typified in the 1944 essay “The Simple Art of Murder”, bases authenticity on style and language rather than on verisimilitude. This conflicting realism undoubtedly explains the halting representations of aging in hard-boiled fiction. The detective’s experience of age can be disavowed with a well-chosen quip or a well-placed right hook. This essay will read this inherent tension—that is, between articulation and renunciation— with respect to male aging within the hard-boiled ethos.

Middle powers have been defined in hierarchical and behavioural terms. They have significantly impacted on the global governance agenda, especially through their leadership within international commissions and through multilateral forums. Recent challenges to multilateralism have created an impression that the middle power moment is over, especially in East Asia. Yet, this article sees a way forward for the stronger, more regionally focused middle powers to continue to influence international governance.

States in the Global South have consistently invested in large-scale, vanity infrastructure projects, which are often not used by the majority of their residents. Using a mixed-method and comparative approach with findings from Greater Maputo, Mozambique, and the Gauteng City-Region exposes how internationally-supported and expensive transport projects do not meet the needs of lower-income urban residents, and meanwhile, widespread, everyday modes of commuting such as trains, paratransit, and pathways for walking deteriorate. State-led development thus often generates an infrastructural landscape characterised by “ruin” and “indifference.” These choices are anachronistic, steeped in a desire for a modernist-inspired future and in establishing narratives of control. In the cases of Gauteng and Maputo, whether or not the infrastructure is “successfully” implemented, these choices have resulted in a distancing of the state from the majority of urban residents.

The adoption of Internet of Things (IoT) sensing devices is growing rapidly due to their ability to provide real-time services. However, it is constrained by limited data storage and processing power. It offloads its massive data stream to edge devices and the cloud for adequate storage and processing. This further leads to the challenges of data outliers, data redundancies, and cloud resource load balancing that would affect the execution and outcome of data streams. This paper presents a review of existing analytics algorithms deployed on IoT-enabled edge cloud infrastructure that resolved the challenges of data outliers, data redundancies, and cloud resource load balancing. The review highlights the problems solved, the results, the weaknesses of the existing algorithms, and the physical and virtual cloud storage servers for resource load balancing. In addition, it discusses the adoption of network protocols that govern the interaction between the three-layer architecture of IoT sensing devices enabled edge cloud and its prevailing challenges. A total of 72 algorithms covering the categories of classification, regression, clustering, deep learning, and optimization have been reviewed. The classification approach has been widely adopted to solve the problem of redundant data, while clustering and optimization approaches are more used for outlier detection and cloud resource allocation.

Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is expansion of the intronic hexanucleotide repeat (GGGGCC) n in C9orf72. Here, we investigate the formation of nucleic acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of ALS/FTD. We observe significant aggregation of the hexanucleotide sequence (GGGGCC) n , which we associate to the formation of multimolecular G-quadruplexes (mG4s) by using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions leads to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validate the biological relevance of our findings by detecting an increased prevalence of G4-structures in C9orf72 mutant human motor neurons when compared to healthy motor neurons by staining with a G4-selective fluorescent probe, revealing signal in putative condensates. Our findings strongly suggest that RNA G-rich repetitive sequences can form protein-free condensates sustained by multimolecular G-quadruplexes, highlighting their potential relevance as therapeutic targets for C9orf72 mutation-related ALS/FTD.

Abstract Seagrass meadows are important sinks for organic carbon and provide co-benefits. However, data on the organic carbon stock in seagrass sediments are scarce for many regions, particularly The Bahamas, which accounts for up to 40.7% of the documented global seagrass area, limiting formulation of blue carbon strategies. Here, we sampled 10 seagrass meadows across an extensive island chain in The Bahamas. We estimate that Bahamas seagrass meadows store 0.42–0.59 Pg organic carbon in the top-meter sediments with an accumulation rate of 2.1–2.9 Tg annually, representing a substantial global blue carbon hotspot. Autochthonous organic carbon in sediments decreased from ~1980 onwards, with concomitant increases in cyanobacterial and mangrove contributions, suggesting disturbance of seagrass ecosystems, likely caused by tourism and maritime traffic activities. This study provides seagrass blue carbon data from a vast, understudied region and contributes to improving climate action for The Bahamas and the Greater Caribbean region.

Abstract Background Cardiovascular diseases (CVD) were responsible for 20.5 million annual deaths globally in 2021, with a disproportionally high burden in sub-Saharan Africa (SSA). There is growing evidence of the use of citizen science and co-design approaches in developing interventions in different fields, but less so in the context of CVD prevention interventions in SSA. This paper reports on the collaborative multi-country project that employed citizen science and a co-design approach to (i) explore CVD risk perceptions, (ii) develop tailored prevention strategies, and (iii) support advocacy in different low-income settings in SSA. Methods This is a participatory citizen science study with a co-design component. Data was collected from 205 participants aged 18 to 75 years in rural and urban communities in Malawi, Ethiopia and Rwanda, and urban South Africa. Fifty-one trained citizen scientists used a mobile app-based (EpiCollect) semi-structured survey questionnaire to collect data on CVD risk perceptions from participants purposively selected from two communities per country. Data collected per community included 100–150 photographs and 150–240 voice recordings on CVD risk perceptions, communication and health-seeking intentions. Thematic and comparative analysis were undertaken with the citizen scientists and the results were used to support citizen scientists-led stakeholder advocacy workshops. Findings are presented using bubble graphs based on weighted proportions of key risk factors indicated. Results Nearly three in every five of the participants interviewed reported having a relative with CVD. The main perceived causes of CVD in all communities were substance use, food-related factors, and litter, followed by physical inactivity, emotional factors, poverty, crime, and violence. The perceived positive factors for cardiovascular health were nutrition, physical activity, green space, and clean/peaceful communities. Multi-level stakeholders (45–84 persons/country) including key decision makers participated in advocacy workshops and supported the identification and prioritization of community-specific CVD prevention strategies and implementation actions. Citizen science-informed CVD risk screening and referral to care interventions were piloted in six communities in three countries with about 4795 adults screened and those at risk referred for care. Health sector stakeholders indicated their support for utilising a citizen-engaged approach in national NCDs prevention programmes. The citizen scientists were excited by the opportunity to lead research and advocacy. Conclusion The collaborative engagement, participatory learning, and co-designing activities enhanced active engagement between citizen scientists, researchers, and stakeholders. This, in turn, provided context-specific insights on CVD prevention in the different SSA settings.

Abstract Chub mackerels (Scomber japonicus) are a migratory marine fish widely distributed in the Indo-Pacific Ocean. They are globally consumed for their high Omega-3 content, but their population is declining due to global warming. Here, we generated the first chromosome-level genome assembly of chub mackerel (fScoJap1) using the Vertebrate Genomes Project assembly pipeline with PacBio HiFi genomic sequencing and Arima Hi-C chromosome contact data. The final assembly is 828.68 Mb with 24 chromosomes, nearly all containing telomeric repeats at their ends. We annotated 31,656 genes and discovered that approximately 2.19% of the genome contained DNA transposon elements repressed within duplicated genes. Analyzing 5-methylcytosine (5mC) modifications using HiFi reads, we observed open/close chromatin patterns at gene promoters, including the FADS2 gene involved in Omega-3 production. This chromosome-level reference genome provides unprecedented opportunities for advancing our knowledge of chub mackerels in biology, industry, and conservation.

Abstract This research paper presents the development of a nonlinear Muskingum model which achieves precise flood routing through river reaches while considering lateral inflow conditions. Fourteen pairs of flood hydrograph found at two specific United States Geological Survey (USGS) stations located along the Red River of the North, namely Grand Forks and Drayton, are used for the calibrations and validations of the Muskingum model. To enhance the accuracy of the procedure, a reach is divided into multiple sub-reaches, and the Muskingum model calculations are performed individually for each interval using the distributed Muskingum method. Notably, the model development process incorporates the use of the Salp Swarm algorithm. The obtained results demonstrate the effectiveness of the developed nonlinear Muskingum model in accurately routing floods through the very gentle river with a bed slope of (0.0002–0.0003). The events were categorized into three groups based on their dominant drivers: Group A (Snowmelt-driven floods), Group B (Rain-on-snow-induced floods), and Group C (Mixed floods influenced by both snowmelt and rainfall). For the sub-reaches in Group A, single sub-reach (NR = 1), the Performance Evaluation Criteria (PEC) yielded the highest value for SSE, amounting to 404.9 × 106. In Group B, when NR = 2, PEC results the highest value were SSE = 730.2 × 106. The number of sub-reaches in a model has a significant influence on parameter estimates and model performance, as demonstrated by the analysis of hydrologic parameters and performance evaluation criteria. Optimal performance varied across case studies, emphasizing the importance of selecting the appropriate number of sub-reaches for peak discharge predictions.

Background: Past research suggests that hormonal migraineurs may have poorer cerebrovascular function than women who do not suffer from migraine. Resveratrol, a vasoactive phytoestrogen, has been shown to improve cerebrovascular function in several populations but has never been tested in hormonal migraineurs. Aim: To investigate the effects of 3-month resveratrol supplementation on the cerebrovascular function of hormonal migraineurs. Methods: We conducted a randomised, double-blind, placebo-controlled, crossover intervention pilot study with resveratrol (150 mg/d for 3 months) in ten hormonal migraineurs (mean age: 37.2 ± 2.6 years). Participants visited the University of Newcastle’s Clinical Nutrition Research Centre where quality of life and disability, and cerebrovascular function were assessed. Quality of life and disability were examined using Migraine-Specific Quality of Life, Headache Impact Test-6 and the Migraine Disability Assessment. Cerebrovascular function was determined using transcranial Doppler ultrasound to bilaterally measure blood flow velocity in the middle and posterior cerebral arteries at rest and in response to a hypercapnic stimulus. Cerebrovascular responsiveness to a cognitive task battery was also measured bilaterally in the middle cerebral arteries. Results: Compared to placebo, blood flow velocity in the right posterior cerebral artery was significantly higher (P = 0.041) following resveratrol supplementation. No other significant differences in cerebrovascular function between resveratrol and placebo treatments were observed. Baseline correlation analyses revealed higher blood flow velocities in the middle and posterior cerebral arteries were associated with better quality of life and less disability. However, higher cerebrovascular responsiveness to hypercapnia in the posterior circulation was associated with higher migraine-related disability and poorer migraine-related quality of life. Conclusion: In this pilot we found evidence that resveratrol may increase blood flow velocity in the right posterior cerebral artery in hormonal migraineurs. Larger cohorts are required confirm this effect and its potential relationship to migraine in premenopausal women.

Abstract NLRP3 induces caspase-1-dependent pyroptotic cell death to drive inflammation. Aberrant activity of NLRP3 occurs in many human diseases. NLRP3 activation induces ASC polymerization into a single, micron-scale perinuclear punctum. Higher resolution imaging of this signaling platform is needed to understand how it induces pyroptosis. Here, we apply correlative cryo-light microscopy and cryo-electron tomography to visualize ASC/caspase-1 in NLRP3-activated cells. The puncta are composed of branched ASC filaments, with a tubular core formed by the pyrin domain. Ribosomes and Golgi-like or endosomal vesicles permeate the filament network, consistent with roles for these organelles in NLRP3 activation. Mitochondria are not associated with ASC but have outer-membrane discontinuities the same size as gasdermin D pores, consistent with our data showing gasdermin D associates with mitochondria and contributes to mitochondrial depolarization.

This research introduces a novel nonlinear Muskingum model for river flood routing, aiming to enhance accuracy in modeling. It integrates lateral inflows using the Whale Optimization Algorithm (WOA) and employs a distributed Muskingum model, dividing river reaches into smaller intervals for precise calculations. The primary goal is to minimize the Sum of Square Errors (SSE) between the observed and modeled outflows. Our methodology is applied to six distinct flood hydrographs, revealing its versatility and efficacy. For Lawler's and Dinavar's flood data, the single-reach Muskingum model outperforms multi-reach versions, demonstrating its effectiveness in handling lateral inflows. For Lawler's data, the single-reach model (NR = 1) yields optimal parameters of K = 0.392, x = 0.027, m = 1.511, and β = 0.010, delivering superior results. Conversely, when fitting flood data from Wilson, Wye, Linsley, and Viessman and Lewis, the multi-reach Muskingum model exhibits better overall performance. Remarkably, the model excels with the Viessman and Lewis flood data, especially with two reaches (NR = 2), achieving a 21.6% SSE improvement while employing the same parameter set. This research represents a significant advancement in flood modeling, offering heightened accuracy and adaptability in river flood routing. HIGHLIGHTS Flooding can have a significant impact on people and environment.; Distributed Muskingum model was introduced to improve the accuracy and efficiency of the model's calculations.; This study suggests WOA to improve the local optimum.; Considering lateral flow is the major feature developed for the new approach in our paper.; The results will be used in Red River of the North to anticipate floods in ND and MN in the US.;

Workers in the trades sectors often experience mental health issues and decreased work ability due to occupational stress, workplace hazards and living in danger or constant fear of injury. Understanding the impacts of psychosocial risk factors on construction workers' mental health can aid in decreasing workplace injuries, lessening disabilities and increasing worker productivity. In this study, we focus on understanding and assessing the mental health and wellness of individuals in the electrical sector that are members of the Employer Engagement Project (EEP) from the Ontario Electrical League (OEL). The subset of potential participants included electricians and plumbers in Ontario working for small to medium sized employers (SME). The recruitment took place in 2022, with a total of 82 participants who completed a survey collecting demographic information, assessing the importance and availability/satisfaction of workplace factors and stress-and burnout-related questions. The data were analyzed using IBM SPSS Statistics 29.0. Two-sample Mann-Whitney U tests were performed to test for associations between the availability of work-related factors and burnout scores among the participants. Burnout scores were determined using the Copenhagen Burnout Inventory. Our findings demonstrate that dissatisfaction of the following factors: Workload allocation, internal staff development opportunity and stable staffing/minimal turnover, were associated with high burnout levels. The findings indicate there may be a relationship between certain work-related factors and burnout levels experienced. There is a need for improvement of workload allocation in SMEs to help enhance the mental health and well-being of employees.

Abstract Spouses may affect each other’s sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r = 0.11; 95% CI = 0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r = −0.11; −0.12, −0.10), which replicated in up to 127,035 23andMe spouse-pairs. Using accelerometer data on 3454 UK Biobank spouse-pairs, the correlation for derived sleep duration was similar to self-report (r = 0.12; 0.09, 0.15). Timing of diurnal activity was positively correlated (r = 0.24; 0.21, 0.27) in contrast to the inverse correlation for chronotype. In Mendelian randomization analysis, positive effects of sleep duration (mean difference=0.13; 0.04, 0.23 SD per SD) and diurnal activity (0.49; 0.03, 0.94) were observed, as were inverse effects of chronotype (−0.15; −0.26, −0.04) and snoring (−0.15; −0.27, −0.04). Findings support the notion that an individual’s sleep may impact that of their partner, promoting opportunities for sleep interventions at the family-level.

Bacterial endosymbionts, in genera Wolbachia and Cardinium, infect various arthropods and some nematode groups. Manipulating these microbial symbionts presents a promising biocontrol strategy for managing disease-causing parasites. However, the diversity of Wolbachia and Cardinium in nematodes remains unclear. This study employed a genome skimming strategy to uncover their occurrence in plant-parasitic nematodes, analyzing 52 populations of 12 species. A metagenome analysis revealed varying endosymbiont genome content, leading to the categorization of strong, weak, and no evidence for endosymbiont genomes. Strong evidence for Wolbachia was found in five populations, and for Cardinium in one population, suggesting a limited occurrence. Strong Wolbachia evidence was noted in Pratylenchus penetrans and Radopholus similis from North/South America and Africa. Heterodera glycines from North America showed strong Cardinium evidence. Weak genomic evidence for Wolbachia was observed in Globodera pallida, Meloidogyne incognita, Rotylenchus reniformis, Pratylechus coffeae, Pratylenchus neglectus, and Pratylenchus thornei; for Cardinium was found in G. pallida, R. reniformis and P. neglectus; 27/52 populations exhibited no endosymbiont evidence. Wolbachia and Cardinium presence varied within nematode species, suggesting non-obligate mutualism. Wolbachia and Cardinium genomes differed among nematode species, indicating potential species-specific functionality. This study advances knowledge of plant-parasitic nematode–bacteria symbiosis, providing insights for downstream eco-friendly biocontrol strategies.

Abstract Background Fluoride is ubiquitous in the United States (US); however, data on biomarkers and patterns of fluoride exposure among US pregnant women are scarce. We examined specific gravity adjusted maternal urinary fluoride (MUFsg) in relation to sociodemographic variables and metal co-exposures among pregnant women in Los Angeles, California. Methods Participants were from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) cohort. There were 293 and 490 women with MUFsg measured during first and third trimesters, respectively. An intra-class correlation coefficient examined consistency of MUFsg between trimesters. Kruskal–Wallis and Mann-Whitney U tests examined associations of MUFsg with sociodemographic variables. Covariate adjusted linear regression examined associations of MUFsg with blood metals and specific gravity adjusted urine metals among a subsample of participants within and between trimesters. A False Discovery Rate (FDR) correction accounted for multiple comparisons. Results Median (IQR) MUFsg was 0.65 (0.5) mg/L and 0.8 (0.59) mg/L, during trimesters one and three respectively. During both trimesters, MUFsg was higher among older participants, those with higher income, and White, non-Hispanic participants than Hispanic participants. MUFsg was also higher for White, non-Hispanic participants than for Black, non-Hispanic participants in trimester three, and for those with graduate training in trimester one. MUFsg was negatively associated with blood mercury in trimester one and positively associated with blood lead in trimester three. MUFsg was positively associated with various urinary metals, including antimony, barium, cadmium, cobalt, copper, lead, nickel, tin, and zinc in trimesters one and/or three. Conclusions MUFsg levels observed were comparable to those found in pregnant women in Mexico and Canada that have been associated with poorer neurodevelopmental outcomes. Lower urinary fluoride levels among Hispanic and non-Hispanic Black participants in MADRES compared to non-Hispanic White participants may reflect lower tap water consumption or lower fluoride exposure from other sources. Additional research is needed to examine whether MUFsg levels observed among pregnant women in the US are associated with neurodevelopmental outcomes.

The Massive open online course (MOOC) is a move toward greater openness in higher education. The current literature on MOOCs, covering research on their effectiveness to accommodate different students’ abilities showed conflicting results in this regard. With limited studies on a MOOC-based flipped classroom in Malaysian higher education, this study explored the perceived usefulness and perceived ease-of-use of the MOOC-based flipped classrooms among the pre-diploma students who enrolled in the English MOOC. The pre-diploma students were interviewed to respond to these concerns. Questionnaires were also administered to all registered users to analyze the perceived use and ease-ofuse of the MOOCs when used in flipped classrooms. The study found the significant challenges faced by pre-diploma students in terms of the content, language, and technical aspects of MOOCs. Therefore, possible solutions to these challenges were identified and discussed. These findings can help the policy makers explore strategies for MOOC's future development, implementation, and success in the context of higher education in Malaysia specifically for pre-diploma students.

Abstract Combining genome assembly with population and functional genomics can provide valuable insights to development and evolution, as well as tools for species management. Here, we present a chromosome-level genome assembly of the common brushtail possum (Trichosurus vulpecula), a model marsupial threatened in parts of their native range in Australia, but also a major introduced pest in New Zealand. Functional genomics reveals post-natal activation of chemosensory and metabolic genes, reflecting unique adaptations to altricial birth and delayed weaning, a hallmark of marsupial development. Nuclear and mitochondrial analyses trace New Zealand possums to distinct Australian subspecies, which have subsequently hybridised. This admixture allowed phasing of parental alleles genome-wide, ultimately revealing at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We find that reprogramming of possum germline imprints, and the wider epigenome, is similar to eutherian mammals except onset occurs after birth. Together, this work is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits.

Abstract One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure.

Abstract Introduction Matrix metalloproteinases (MMPs) play a pathophysiological role in cancer initiation and progression. Numerous studies have examined an association between MMP-2, MMP-9, and MMP-11 expression and clinicopathological characteristics of breast cancer (BC); however, no research has been done on the MMP expression levels in BC cases from Ethiopia. Materials and methods A total of 58 formalin-fixed paraffin-embedded breast tissue samples encompassing 16 benign breast tumors and 42 BC were collected. The RNA was extracted and quantitative reverse-transcription PCR was performed. GraphPad Prism version 8.0.0 was used for statistical analysis. Results The MMP-11 expression levels were significantly higher in breast cancer cases than in benign breast tumors (P = 0.012). Additionally, BC cases with positive lymph nodes and ER-positive receptors had higher MMP-11, MMP-9, and MMP-2 expression than cases with negative lymph nodes and ER-negative, respectively. The MMP-11 and MMP-9 expressions were higher in grade III and luminal A-like tumors than in grade I-II and other subtypes, respectively. Conclusion The MMP-11 expression was higher in BC than in benign breast tumors. Additionally, MMP-11, MMP-9, and MMP-2 were higher in BC with positive lymph nodes and estrogen receptors. Our findings suggest an important impact of MMPs in BC pathophysiology, particularly MMP-11.

Abstract Background Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, and repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying ASD both in Qatar and the greater Middle East has been largely unexplored. Here, we describe the first genomic data release from the BARAKA-Qatar Study—a nationwide program building a broadly consented biorepository of individuals with ASD and their families available for sample and data sharing and multi-omics research. Methods In this first release, we present a comprehensive analysis of whole-genome sequencing (WGS) data of the first 100 families (372 individuals), investigating the genetic architecture, including single-nucleotide variants (SNVs), copy number variants (CNVs), tandem repeat expansions (TREs), as well as mitochondrial DNA variants (mtDNA) segregating with ASD in local families. Results Overall, we identify potentially pathogenic variants in known genes or regions in 27 out of 100 families (27%), of which 11 variants (40.7%) were classified as pathogenic or likely-pathogenic based on American College of Medical Genetics (ACMG) guidelines. Dominant variants, including de novo and inherited, contributed to 15 (55.6%) of these families, consisting of SNVs/indels (66.7%), CNVs (13.3%), TREs (13.3%), and mtDNA variants (6.7%). Moreover, homozygous variants were found in 7 families (25.9%), with a sixfold increase in homozygous burden in consanguineous versus non-consanguineous families (13.6% and 1.8%, respectively). Furthermore, 28 novel ASD candidate genes were identified in 20 families, 23 of which had recurrent hits in MSSNG and SSC cohorts. Conclusions This study illustrates the value of ASD studies in under-represented populations and the importance of WGS as a comprehensive tool for establishing a molecular diagnosis for families with ASD. Moreover, it uncovers a significant role for recessive variation in ASD architecture in consanguineous settings and provides a unique resource of Middle Eastern genomes for future research to the global ASD community.

Abstract Introduction Head and neck cancer (HNC) is the eighth most common cancer in the United Kingdom. Survival rates improve when the cancer is diagnosed at an early stage, highlighting a key need to identify at‐risk patients. This study aimed to explore opportunistic HNC identification and referral by community pharmacists (CPs) using a symptom‐based risk assessment calculator, from the perspective of patients with a diagnosis of HNC. Methods Purposive sampling was used to recruit patients from the HNC pathway in three large teaching hospitals in Northern England. Qualitative methodology was used to collect data through an iterative series of semistructured telephone interviews. Framework analysis was utilised to identify key themes. Results Four main themes were constructed through the analytic process: (1) HNC presentation and seeking help; (2) the role of the CP; (3) public perception of HNC and (4) the role of a symptom‐based risk calculator. Participants agreed that CPs could play a role in the identification and referral of suspected HNCs, but there were concerns about access as patients frequently only encounter the medicine counter assistant when they visit the pharmacy. HNC symptoms are frequently attributed to common or minor conditions initially and therefore considered not urgent, leading to delays in seeking help. While there is public promotion for some cancers, there is little known about HNC. Early presentation of HNC can be quite variable, therefore raising awareness would help. The use of a symptom‐based risk calculator was considered beneficial if it enabled earlier referral and diagnosis. Participants suggested that it would also be useful if the public were made aware of it and could self‐assess their symptoms. Conclusion In principle, CPs could play a role in the identification and referral of HNC, but there was uncertainty as to how the intervention would work. Future research is needed to develop an intervention that would facilitate earlier identification and referral of HNC while not disrupting CP work and that would promote HNC and the risk calculator more widely. Patient or Public Contribution Patient and public involvement and engagement (PPIE) was integrated throughout the project. Initially, the proposal was discussed during a Cancer Head and Neck Group Experience (CHANGE) PPIE meeting. CHANGE was set up to support HNC research in 2018. The group is composed of seven members (four female, three male) with an age range of 50–71 years, who were diagnosed at Sunderland Royal Hospital. A patient representative from the University of Sunderland PPIE group and a trustee of the Northern HNC Charity were recruited as co‐applicants. They attended project management group meetings and reviewed patient‐facing documentation.