Association of per- and polyfluoroalkyl substances with the antioxidant bilirubin across pregnancy.

BACKGROUND: In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy. METHODS: The study population included 332 participants in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Serum samples were collected up to two times (early pregnancy: 6-18 gestational weeks; late pregnancy: 21-36 gestational weeks) for the measurement of perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and total bilirubin. We analyzed single PFAS with linear mixed effect regression and a mixture of the four PFAS with quantile g-computation. Models were repeated with a multiplicative interaction term to explore effect modification by study visit. RESULTS: Overall, PFHxS was positively associated with bilirubin (ß = 0.08, 95 % CI = 0.01, 0.15). We also found during late pregnancy, there was a positive association of PFHxS and the PFAS mixture with bilirubin (ß = 0.12, 95 % CI = 0.02, 0.22; ψ = 0.19, 95 % CI = 0.03, 0.34, respectively). Finally, study visit modified the PFOA-bilirubin association (interaction p-value = 0.09), which was greater during early pregnancy (ß = 0.08, 95 % CI = 0.01, 0.15). CONCLUSION: In a prospective cohort of pregnant African Americans, an increase in PFOA, PFHxS, and the PFAS mixture was associated with an increase in bilirubin. Our results suggest that, depending on pregnancy stage, prenatal PFAS exposure disrupts the maternal liver antioxidant capacity.

Two novel Pleosporales species isolated from the bark of Acer saccharum.

During a survey of culturable microfungi from the bark of sugar maple (Acer saccharum), Atrocalyx glutinosus and Nigrograna rubescens, two novel species of Pleosporales (Dothideomycetes) were isolated from several locations in eastern Ontario, Canada. Formal species descriptions are presented based on unique colony phenotypes and micromorphological characteristics and supported using multi-locus molecular phylogenetic comparisons with similar species. Both A. glutinosus and N. rubescens produce pycnidial asexual morphs in culture. As their names imply, under specific culture conditions, A. glutinosus excretes large amounts of the glutinous polysaccharide pullulan and N. rubescens produces a dark red naphthoquinone pigment that diffuses in the culture medium. Citation: Mack JN, Sproule A, Shields SW, Seifert KA, Smith M, Overy DP (2024). Two novel Pleosporales species isolated from the bark of Acer saccharum . Fungal Systematics and Evolution 13: 1-14. doi: 10.3114/fuse.2024.13.01.

Adolescents' unhealthy snacking behaviour during the school journey and the association with transport modes and food outlets along the school route.

AIMS: Active transport to and from school provides an opportunity for adolescents to engage in physical activity, but travelling through an obesogenic environment may have unintended consequences on their snacking behaviour. This study aimed to: (1) identify whether adolescents' unhealthy snacking behaviour was associated with school transport modes and food outlets on their estimated school route and (2) explore whether food outlet density on the school route differed between school transport modes. METHODS: Adolescents (n = 406; aged 15.1 ± 1.4 years; 50.7% boys; 63.5% New Zealand European) from all 12 secondary schools in Dunedin city, Aotearoa New Zealand, completed an online survey. School transport modes (active, motorised or mixed) and unhealthy snacking data were collected. Food outlet data were collected using Google Places Application Programming Interface (API). Home-to-school route and distance were estimated using geographical information system (GIS) analysis based on a walkable road network. Data were analysed using the chi-square test and logistic regression. RESULTS: Overall, 26.4% of adolescents reported purchasing and consuming unhealthy snacks or soft drinks on the way to school and 41.4% from school. The odds of unhealthy snacking during the school journey was higher among mixed transport users than active transport users on the way to (odds ratio (OR) = 2.73, 95% confidence interval (CI) = 1.39-5.36) and from school (OR = 2.68, 95% CI = 1.40-5.13). No differences were observed by food outlet type. There were no food outlets on the estimated school route for 44.8% of adolescents. The presence of more than one food outlet per kilometre of the estimated school route differed between active (38.7%), motorised (42.6%) and mixed transport users (46.4%; p = 0.006). CONCLUSION: School transport modes were significantly associated with adolescents' unhealthy snacking behaviour and food outlets on their school journey. Policy measures which minimise exposure to unhealthy food outlets may reduce unhealthy snacking among adolescents.

Patient experiences with blood pressure measurement methods for hypertension diagnosis: Qualitative findings from the BP-CHECK study.

BACKGROUND: Out-of-office blood pressure (BP) measurement is recommended when making a new hypertension diagnosis. In practice, however, hypertension is primarily diagnosed using clinic BP. The study objective was to understand patient attitudes about accuracy and patient-centeredness regarding hypertension diagnostic methods. METHODS: Qualitative study within a randomized controlled diagnostic study conducted between May 2017 and March 2019 comparing the accuracy and acceptability of BP measurement methods among patients in an integrated healthcare delivery system. All participants completed 24-hour ambulatory blood pressure monitoring (ABPM), plus either clinic BP, home BP monitoring (HBPM), or kiosk BP diagnostic testing. Qualitative interviewees (aged 31-76 years, n=35) were recruited from the main study. RESULTS: Participants who completed HBPM found it to be comfortable and low burden, and believed it produced accurate results. Participants in the clinic arm described clinic measurements as inconvenient. Participants in the kiosk arm overall did not favor kiosks due to concerns about accuracy and privacy. Participants described ABPM as the most accurate method due to repeated measurements over the 24-hour period in real-world contexts, but many found it uncomfortable and disruptive. Participants also noted methods that involved repeated measures such as HBPM and ABPM particularly influenced their understanding of whether or not they had hypertension. CONCLUSIONS: Hypertension diagnostic methods that include more BP measurements help patients gain a deeper understanding of BP variability and the lower reliability of infrequent measurements in clinic. These findings warrant implementing strategies to enhance out-office BP diagnostic testing in primary care.

The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

Shorter Telomere Length Is Associated With Older Age, Poor Sleep Hygiene, and Orthopedic Injury, but Not Mild Traumatic Brain Injury, in a Cohort of Canadian Children.

BACKGROUND: Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI). METHODS: Saliva was collected at a postacute (median 7 days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17 years with either mTBI (n = 202) or OI (n = 90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman's correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates. RESULTS: After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio = 0.93; 95% confidence interval, 0.89-0.98; P = .003). As expected, increasing age was negatively associated with TL (Spearman's r = -0.14, P = .016). Sleep hygiene at 3 months was positively associated with TL (adjusted mean ratio = 1.010; 95% confidence interval, 1.001-1.020; P = .039). CONCLUSION: The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.

Severe outcomes among adults with TB during COVID-19.

BACKGROUND: The COVID-19 pandemic prompted strict public health measures to reduce SARS-CoV-2 transmission, potentially interrupting TB programmes in the Western Cape, South Africa. METHODS: We conducted a retrospective cohort study, estimating changes in new TB case rates and risk of death during TB-specific admissions within 6 months of TB first evidence, during the pre-pandemic (1 January 2019-26 March 2020) and after the implementation of public health and social measures (PHSM) periods (26 March 2020-30 September 2021), based on PHSM strictness. We used interrupted time series and logistic regression models to adjust for key characteristics. RESULTS: We found an average 22% reduction (95% CI 19-25) in monthly TB cases during the entire PHSM implementation period. Additionally, the risk of death during TB-specific admissions increased, with the adjusted odds ratio ranging across PHSM levels from 1.36 (95% CI 1.17-1.57) on Level 1 to 1.44 (95% CI 1.16-1.79) on Level 2 compared with the pre-pandemic period. CONCLUSIONS: There was a decline in the number of diagnosed TB cases and an increased risk of severe outcomes from 26 March 2020 to 30 September 2021 in the Western Cape. TB programme recovery strategies must be prioritised, and TB management programmes must be integrated into future pandemic responses.

CONTEXTE: La pandémie de COVID-19 a entraîné la mise en place de mesures de santé publique strictes afin de limiter la propagation du SRAS-CoV-2, ce qui risque de perturber les efforts de lutte contre la TB dans la province du Cap-Occidental, en Afrique du Sud. MÉTHODES: Une étude de cohorte rétrospective a été réalisée afin d'évaluer les variations des taux de nouveaux cas de TB et le risque de décès lors des admissions spécifiques à la TB dans les 6 mois suivant la première preuve de la maladie. Cette étude a été menée pendant deux périodes distinctes : la période prépandémique, allant du 1er janvier 2019 au 26 mars 2020, et la période post-mise en œuvre des mesures de santé publique et sociales (PHSM, pour l'anglais « public health and social measures ¼), allant du 26 mars 2020 au 30 septembre 2021. L'objectif était d'évaluer l'impact des PHSM sur ces indicateurs. Pour ce faire, des séries temporelles interrompues et des modèles de régression logistique ont été utilisés afin de prendre en compte les principales caractéristiques. RÉSULTATS: Au cours de la période de mise en œuvre des PHSM, nous avons observé une diminution moyenne de 22% (IC à 95% 19­25) des cas mensuels de TB. De plus, nous avons constaté une augmentation du risque de décès pendant les admissions pour TB, avec un rapport de cotes ajusté variant de 1,36 (IC à 95% ; 1,17­1,57) au niveau 1 des PHSM à 1,44 (IC à 95% ; 1,16­1,79) au niveau 2, par rapport à la période prépandémique. CONCLUSIONS: Entre le 26 mars 2020 et le 30 septembre 2021, il y a eu une baisse du nombre de cas de TB diagnostiqués dans la province du Cap-Occidental, mais le risque de résultats graves a augmenté pendant cette période. Les stratégies de rétablissement des programmes de lutte contre la TB doivent être prioritaires et les programmes de gestion de la TB doivent être intégrés dans les futures réponses à la pandémie.

A new interpretation of Pikaia reveals the origins of the chordate body plan.

Our understanding of the evolutionary origin of Chordata, one of the most disparate and ecologically significant animal phyla, is hindered by a lack of unambiguous stem-group relatives. Problematic Cambrian fossils that have been considered as candidate chordates include vetulicolians,1Yunnanozoon,2 and the iconic Pikaia.3 However, their phylogenetic placement has remained poorly constrained, impeding reconstructions of character evolution along the chordate stem lineage. Here we reinterpret the morphology of Pikaia, providing evidence for a gut canal and, crucially, a dorsal nerve cord-a robust chordate synapomorphy. The identification of these structures underpins a new anatomical model of Pikaia that shows that this fossil was previously interpreted upside down. We reveal a myomere configuration intermediate between amphioxus and vertebrates and establish morphological links between Yunnanozoon, Pikaia, and uncontroversial chordates. In this light, we perform a new phylogenetic analysis, using a revised, comprehensive deuterostome dataset, and establish a chordate stem lineage. We resolve vetulicolians as a paraphyletic group comprising the earliest diverging stem chordates, subtending a grade of more derived stem-group chordates comprising Yunnanozoon and Pikaia. Our phylogenetic results reveal the stepwise acquisition of characters diagnostic of the chordate crown group. In addition, they chart a phase in early chordate evolution defined by the gradual integration of the pharyngeal region with a segmented axial musculature, supporting classical evolutionary-developmental hypotheses of chordate origins4 and revealing a "lost chapter" in the history of the phylum.

First Study of the

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

Development of a Novel Non-invasive Metabolomics Assay to Predict Implantation Potential of Human Embryos.

Can a set of metabolites present in embryo culture media correlate with embryo implantation? Case-control study in two phases: discovery phase (101 samples) and validation phase (169 samples), collected between 2018 and 2022, with a total of 218 participants. Culture media samples with known implantation outcomes were collected after blastocyst embryo transfer (including both PGT and non-PGT cycles) and were analyzed using chromatography followed by mass spectrometry. The spectra were processed and analyzed using statistical and machine learning techniques to identify biomarkers associated with embryo implantation, and to develop a predictive model. In the discovery phase, 148 embryo implantation biomarkers were identified using high resolution equipment, and 47 of them were characterized. Our results indicate a significant enrichment of tryptophan metabolism, arginine and proline metabolism, and lysine degradation biochemical pathways. After transferring the method to a lower resolution equipment, a model able to assign a Metabolite Pregnancy Index (MPI) to each embryo culture media was developed, taking the concentration of 36 biomarkers as input. Applying this model to 20% of the validation samples (N=34) used as the test set, an accuracy of 85.29% was achieved, with a PPV (Positive Predictive Value) of 88% and a NPV (Negative Predictive Value) of 77.78%. Additionally, informative results were obtained for all the analyzed samples. Metabolite concentration in the media after in vitro culture shows correlation with embryo implantation potential. Furthermore, the mathematical combination of biomarker concentrations using Artificial Intelligence techniques can be used to predict embryo implantation outcome with an accuracy of around 85%.

Occupational health screening during Gurkha Central Selection: a retrospective cohort study.

OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.

Supportive Care of Hematopoietic Stem Cell Donors.

Supportive care needs for hematopoietic stem cell recipients have been studied. Less is known about the care needs of stem cell donors. Care challenges arise at donor selection, preparation for the donation, the donation procedure and the immediate and long-term after-care. Care needs were analyzed for 1,831 consecutive bone marrow and peripheral stem cell donors at MedStar Georgetown University Hospital between January 2018 and August 2023 in support of a review of the current literature. During the selection, related donors may experience psychological pressures affecting their motivation, while donation centers may be willing to accept co-morbidities in these donors which might preclude donation in unrelated peers. For bone marrow donations, it is important to select donors not only according to optimal genetic matching criteria but also according to suitable donor/recipient weight ratios, to facilitate sufficient stem cell yields. During the donation preparation phase, side effects and complications related to stem cell stimulation must be anticipated and managed for peripheral cell donors, while the pros and cons of autologous blood donation should be evaluated carefully for bone marrow donors. The stem cell donation procedure itself carries potential side effects and complications as well. Peripheral cell donors may require a central line and may encounter hypocalcemia, thrombocytopenia, and anemia. Bone marrow donors face risks associated with anesthesia, blood loss and pain. Post-procedure care focusses on pain management, blood cell recovery and the psychological support necessary to regain a high quality-of-life existence. Hematopoietic stem donors are giving part of themselves to save another's life. They deserve comprehensive supportive care to accompany them throughout the donation process.

A dedicated quality improvement programme can increase access to paediatric minimal access surgery in South Africa.

BACKGROUND: In this project, we reviewed our experience in minimal access paediatric surgery (MAPS) at Greys Hospital over the last decade. This information would provide an overview of our experience and would enable us to identify areas where we can strengthen our surgical service and our training programme. METHODS: All surgical patients are captured in the hybrid electronic medical registry (HEMR). All patients aged 18 years or less who underwent a MAPS procedure between 2012 and 2021 were reviewed. Data collected included demographic information, type of surgery, nature of the surgery (elective or emergency), organ system operated on, whether trainees or consultants performed the surgeries and the morbidities and mortalities experienced. Statistical analysis included linear regression and ANOVA, which was performed using Jamovi software. RESULTS: A total of 1 328 MAPS procedures were performed on 994 patients over nine years. There were 359 female and 635 male patients. There was a steady increase in the number of cases performed per year. The age of the patients ranged from one day of life to 18 years, with a median of 8 years. The multiple linear regression results indicated a very strong collective significant effect between the courses performed, the number of consultants, and the MAPS cases performed. The ANOVA test for the individual factors was not statistically significant, but there was a very strong combined correlation with an r-value of 0.87 and a p-value of 0.014 using the overall model test. The consultants' training also directly impacted on the teaching and training of registrars, with progressively more cases being performed by trainees over the years. Postoperative morbidity was reported in 40 patients. The morbidity rate was three per cent. There were no mortalities. CONCLUSION: It is feasible to deliver MAPS to children in our environment. A comprehensive quality improvement strategy has yielded satisfying results. The increased use of MAPS has resulted in a general transfer of skills to junior staff. Ongoing efforts to support the rollout of MAPS in children are warranted.

Differences in Perceptions of COVID-19 Risks in a Fishing Community in Alaska, 2020-2021.

Bristol Bay in Alaska is home to the world's largest commercial salmon fishery. During an average fishing season, the population of the Bristol Bay region more than doubles as thousands of workers from out of state converge on the fishery. In the months leading up to the 2020 commercial fishery opening, as the COVID-19 pandemic exploded worldwide, great uncertainty existed about the health risks of opening the fishery. Bristol Bay residents had not yet experienced any cases of COVID-19, yet the livelihoods of most were closely tied to the commercial fishery opening. To better understand how COVID-19 risk perceptions affected decisions to participate in the fishery, we administered an online survey to community members and fishery participants. We collected standard socioeconomic data and posed questions to gauge risk perceptions related to COVID-19. We find that COVID-19 risk perceptions vary across race/ethnic groups by residency and income. People with below median income who are members of minority groups-notably, non-resident Hispanic workers and resident Alaska Native respondents-reported the highest risk perceptions related to COVID-19. This study highlights the important linkages among risk perceptions, socioeconomic characteristics, and employment decisions during an infectious disease outbreak.

Observation of New Isotopes in the Fragmentation of

Five previously unknown isotopes (^{182,183}Tm, ^{186,187}Yb, ^{190}Lu) were produced, separated, and identified for the first time at the Facility for Rare Isotope Beams (FRIB) using the Advanced Rare Isotope Separator (ARIS). The new isotopes were formed through the interaction of a ^{198}Pt beam with a carbon target at an energy of 186 MeV/u and with a primary beam power of 1.5 kW. Event-by-event particle identification of A, Z, and q for the reaction products was performed by combining measurements of the energy loss, time of flight, magnetic rigidity Bρ, and total kinetic energy. The ARIS separator has a novel two-stage design with high resolving power to strongly suppress contaminant beams. This successful new isotope search was performed less than one year after FRIB operations began and demonstrates the discovery potential of the facility which will ultimately provide 400 kW of primary beam power.

Repeated exposure to eucalyptus wood smoke alters pulmonary gene and metabolic profiles in male Long-Evans rats.

Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters.

What sexual and reproductive health issues do young people want to discuss with a doctor, and why haven't they done so? Findings from an online survey.

OBJECTIVE: Young people are a priority group for sexual and reproductive health (SRH) care. We considered which SRH topics young Australians want to discuss with a general practitioner (GP) and explored barriers they encounter to discussing these issues. METHODS: We conducted an online survey (2nd May - 21st June 2022) of Australians aged 16-29 years. Participants were asked to identify from a list of SRH topics which they wanted to discuss, but never had, with a GP. Those who selected any topic/s (with 'undiscussed SRH issues') were asked a free-text follow-up question about what prevented them from discussing issues. We explored characteristics associated with having undiscussed issues using multivariate logistic regression. Free-text comments were analysed using content analysis. RESULTS: A total of 1887 people completed relevant survey questions. Most (67.1 %) were women and 48.5 % were heterosexual. Two-thirds (67.0 %) had a usual GP. Nearly half (45.6 %) had undiscussed issues. Most commonly, women wanted to discuss cervical screening and sexual problems, and men wanted to discuss sexual problems and STIs. Participants who were male, older, heterosexual, and with a usual GP were least likely to have undiscussed issues. Barriers to accessing care for SRH were identified from free-text comments, including discomfort, lack of opportunity, fear of negative outcomes, low priority of SRH issues, and perceptions about the role and expertise of GPs. CONCLUSIONS: Many young people would welcome more preventative SRH care. Young people may be reassured that all issues, including sexual difficulties and dysfunction, are appropriate to discuss with a GP.

Demonstrating the reliability of in vivo metabolomics based chemical grouping: towards best practice.

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography-mass spectrometry (LC-MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice.