Behaviour change intervention (education and text) to prevent dental caries in secondary school pupils: BRIGHT RCT, process and economic evaluation.

Background: The presence of dental caries impacts on children's daily lives, particularly among those living in deprived areas. There are successful interventions across the United Kingdom for young children based on toothbrushing with fluoride toothpaste. However, evidence is lacking for oral health improvement programmes in secondary-school pupils to reduce dental caries and its sequelae. Objectives: To determine the clinical and cost effectiveness of a behaviour change intervention promoting toothbrushing for preventing dental caries in secondary-school pupils. Design: A multicentre, school-based, assessor-blinded, two-arm cluster randomised controlled trial with an internal pilot and embedded health economic and process evaluations. Setting: Secondary schools in Scotland, England and Wales with above-average proportion of pupils eligible for free school meals. Randomisation occurred within schools (year-group level), using block randomisation stratified by school. Participants: Pupils aged 11-13 years at recruitment, who have their own mobile telephone. Interventions: Two-component intervention based on behaviour change theory: (1) 50-minute lesson delivered by teachers, and (2) twice-daily text messages to pupils' mobile phones about toothbrushing, compared with routine education. Main outcome measures: Primary outcome: presence of at least one treated or untreated carious lesion using DICDAS4-6MFT (Decayed, Missing and Filled Teeth) in any permanent tooth, measured at pupil level at 2.5 years. Secondary outcomes included: number of DICDAS4-6MFT; presence and number of DICDAS1-6MFT; plaque; bleeding; twice-daily toothbrushing; health-related quality of life (Child Health Utility 9D); and oral health-related quality of life (Caries Impacts and Experiences Questionnaire for Children). Results: Four thousand six hundred and eighty pupils (intervention, n = 2262; control, n = 2418) from 42 schools were randomised. The primary analysis on 2383 pupils (50.9%; intervention 1153, 51.0%; control 1230, 50.9%) with valid data at baseline and 2.5 years found 44.6% in the intervention group and 43.0% in control had obvious decay experience in at least one permanent tooth. There was no evidence of a difference (odds ratio 1.04, 95% confidence interval 0.85 to 1.26, p = 0.72) and no statistically significant differences in secondary outcomes except for twice-daily toothbrushing at 6 months (odds ratio 1.30, 95% confidence interval 1.03 to 1.63, p = 0.03) and gingival bleeding score (borderline) at 2.5 years (geometric mean difference 0.92, 95% confidence interval 0.85 to 1.00, p = 0.05). The intervention had higher incremental mean costs (£1.02, 95% confidence interval -1.29 to 3.23) and lower incremental mean quality-adjusted life-years (-0.003, 95% confidence interval -0.009 to 0.002). The probability of the intervention being cost-effective was 7% at 2.5 years. However, in two subgroups, pilot trial schools and schools with higher proportions of pupils eligible for free school meals, there was an 84% and 60% chance of cost effectiveness, respectively, although their incremental costs and quality-adjusted life-years remained small and not statistically significant. The process evaluation revealed that the intervention was generally acceptable, although the implementation of text messages proved challenging. The COVID-19 pandemic hampered data collection. High rates of missing economic data mean findings should be interpreted with caution. Conclusions: Engagement with the intervention and evidence of 6-month change in toothbrushing behaviour was positive but did not translate into a reduction of caries. Future work should include work with secondary-school pupils to develop an understanding of the determinants of oral health behaviours, including toothbrushing and sugar consumption, particularly according to free school meal eligibility. Trial registration: This trial is registered as ISRCTN12139369. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/166/08) and is published in full in Health Technology Assessment; Vol. 28, No. 52. See the NIHR Funding and Awards website for further award information.

Tooth decay has an impact on children and young people's daily lives, particularly those living in deprived areas. For young children, programmes to improve toothbrushing with fluoride toothpaste help prevent tooth decay. The Brushing RemInder 4 Good oral HealTh trial (BRIGHT) investigated whether a secondary-school-based toothbrushing programme would work. We developed a new programme which included a lesson and twice-daily text messages sent to pupils' phones. In total, 4680 pupils, aged 11­13 years, from 42 secondary schools in the United Kingdom took part in the trial. At each school, one year group was randomly selected to receive the programme, while the other year group did not receive it. All pupils were followed up for 2.5 years to see whether there were any differences in levels of tooth decay, frequency of toothbrushing, plaque or quality of life. We also considered the programme's value for money and the views of pupils and school staff. We followed up 2383 pupils and found no difference in tooth decay, plaque or quality of life. We found those who had the programme were more likely to brush their teeth twice daily after 6 months than those who did not. The programme was not good value for money overall. However, the programme appeared to be of more benefit at preventing tooth decay in pupils eligible for free school meals compared to those not eligible. In the schools with more pupils eligible for free school meals, the chance of the programme representing good value for money increased. The programme was generally liked by the pupils and school staff. Some pupils found the text messages useful, although others said they were annoying. The programme helped pupils brush their teeth more frequently in the short term, but this did not lead to less tooth decay. Further research is needed to understand how to prevent tooth decay in secondary-school pupils.

Prevalence and associated risk factors with unawareness of folic acid benefits prior to pregnancy: Results from Canadian Community Health Survey.

Recent national studies on awareness of folic acid (FA) prior to pregnancy among Canadian women are lacking. Using the 2017-18 Canadian Community Health Survey, we aimed to estimate prevalence and risk factors associated with Canadian women who reported they were unaware of benefits of FA supplementation before pregnancy. Prevalence of unawareness of FA was 22.1%. Lower education, lack of a health care provider, low household income, and an immigrant background were associated with greater odds of unawareness of benefits of FA supplementation. Persistent associations with measures of social disadvantage and social determinants of health emphasize the need for new targeted public health campaigns.

Role of circulating T follicular helper subsets following Ty21a immunization and oral challenge with wild type S. Typhi in humans.

Despite decades of intense research, our understanding of the correlates of protection against Salmonella Typhi (S. Typhi) infection and disease remains incomplete. T follicular helper cells (TFH), an important link between cellular and humoral immunity, play an important role in the development and production of high affinity antibodies. While traditional TFH cells reside in germinal centers, circulating TFH (cTFH) (a memory subset of TFH) are present in blood. We used specimens from a typhoid controlled human infection model whereby participants were immunized with Ty21a live attenuated S. Typhi vaccine and then challenged with virulent S. Typhi. Some participants developed typhoid disease (TD) and some did not (NoTD), which allowed us to assess the association of cTFH subsets in the development and prevention of typhoid disease. Of note, the frequencies of cTFH were higher in NoTD than in TD participants, particularly 7 days after challenge. Furthermore, the frequencies of cTFH2 and cTFH17, but not cTFH1 subsets were higher in NoTD than TD participants. However, we observed that ex-vivo expression of activation and homing markers were higher in TD than in NoTD participants, particularly after challenge. Moreover, cTFH subsets produced higher levels of S. Typhi-specific responses (cytokines/chemokines) in both the immunization and challenge phases. Interestingly, unsupervised analysis revealed unique clusters with distinct signatures for each cTFH subset that may play a role in either the development or prevention of typhoid disease. Importantly, we observed associations between frequencies of defined cTFH subsets and anti-S. Typhi antibodies. Taken together, our results suggest that circulating TFH2 and TFH17 subsets might play an important role in the development or prevention of typhoid disease. The contribution of these clusters was found to be distinct in the immunization and/or challenge phases. These results have important implications for vaccines aimed at inducing long-lived protective T cell and antibody responses.

Live birth after transmyometrial embryo transfer in a patient with radical trachelectomy.

OBJECTIVE: To report the successful utilization of transmyometrial embryo transfer (TMET) in a patient with a history of radical trachelectomy. DESIGN: Video article. SETTING: Academic fertility center. PATIENT(S): A 39-year-old, para 1, woman with a history of radical trachelectomy and abdominal cerclage presented with secondary infertility. Her previous pregnancy was conceived naturally. Her first in vitro fertilization (IVF) cycle yielded only one day 7 euploid blastocyst. All attempts at performing mock embryo transfers, cervical dilatation, and hysteroscopy were unsuccessful because of absence of clinically identifiable cervical tissue. The euploid embryo was transferred into a gestational carrier; however, this resulted in a biochemical pregnancy. She underwent a second IVF cycle that yielded one day 5 euploid blastocyst. Given her history, TMET was planned. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (e.g., PubMed, ScienceDirect, and Scopus) and other applicable sites. INTERVENTION(S): Transmyometrial embryo transfer using the Towako catheter. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, and live birth. RESULT(S): After institutional and Health Canada approval of the Towako catheter, a transvaginal ultrasound-guided TMET was performed under sedation with intravenous midazolam and fentanyl. The day 5 euploid blastocyst from the second IVF cycle was transferred, and the patient's ß-human chorionic gonadotropin levels 9 and 11 days after TMET were 86 and 262 IU/L, respectively. A single intrauterine pregnancy with cardiac activity of 119 beats/min was noted at a gestational age of 7 weeks and 2 days. The patient delivered a live singleton at 35 weeks and 2 days weighing 2,182 g. CONCLUSION(S): Transmyometrial embryo transfer is a useful clinical technique for transferring embryos in patients with acquired or congenital cervical issues in whom transcervical embryo transfer is either very difficult or impossible.

Optically accessible long-lived electronic biexcitons at room temperature in strongly coupled H- aggregates.

Photon absorption is the first process in light harvesting. Upon absorption, the photon redistributes electrons in the materials to create a Coulombically bound electron-hole pair called an exciton. The exciton subsequently separates into free charges to conclude light harvesting. When two excitons are in each other's proximity, they can interact and undergo a two-particle process called exciton-exciton annihilation. In this process, one electron-hole pair spontaneously recombines: its energy is lost and cannot be harnessed for applications. In this work, we demonstrate the creation of two long-lived excitons on the same chromophore site (biexcitons) at room temperature in a strongly coupled H-aggregated zinc phthalocyanine material. We show that exciton-exciton annihilation is suppressed in these H- aggregated chromophores at fluences many orders of magnitudes higher than solar light. When we chemically connect the same aggregated chromophores to allow exciton diffusion, we observe that exciton-exciton annihilation is switched on. Our findings demonstrate a chemical strategy, to toggle on and off the exciton-exciton annihilation process that limits the dynamic range of photovoltaic devices.

Mechanisms and risk factors associated with spinal cord injury, facet fracture, and level of dislocation, in occupants with cervical spine dislocations sustained in motor vehicle crashes.

OBJECTIVE: Motor vehicle crashes (MVCs) are the leading cause of cervical spine dislocation. The mechanisms underlying this injury are unclear, limiting the development of injury prevention devices and strategies. MVC databases contain occupant, medical, vehicle, and crash details that are not routinely collected elsewhere, providing a unique resource for investigating injury mechanisms and risk factors. In this study, a comprehensive standalone analysis of cervical spine dislocations captured in MVC databases was performed. METHODS: Epidemiologic, biomechanical, and injury data were extracted from three MVC databases. Logistic regression models were developed to determine the occupant, vehicle, and crash characteristics, as well as the global (inertial or impact) and regional (flexion, compression, etc.) loading mechanisms associated with the level of cervical spine dislocation (axial or sub-axial), and the occurrence of spinal cord injury (SCI) or facet fracture concomitant to dislocation. RESULTS: There was no association between global or regional injury mechanisms and the level of cervical spine dislocation. Sub-axial dislocations were typically due to head/face impact with the airbag or upper interior components, or a result of seatbelt restraint of the torso. Higher occupant age, lower BMI, partial/no ejection, and frontal and side configuration crashes (compared to rollovers) were associated with a higher likelihood of sub-axial, versus axial, dislocation. Amongst all dislocations, an increased likelihood of SCI was associated with impact injuries, airbag non-deployment, and complete ejection, while concomitant facet fracture was associated with the presence of regional compression. Severe crashes, partial ejections, and "utility vehicles" and "vans and trucks" (compared with "passenger vehicles") were associated with a higher risk of facet fracture concomitant to sub-axial dislocation. CONCLUSION: The findings of this study may be used to inform the loading modes to be simulated in future ex vivo or computational models seeking a better understanding of cervical spine dislocations.

Facet deflection and strain are dependent on axial compression and distraction in C5-C7 spinal segments under constrained flexion.

Background: Facet fractures are frequently associated with clinically observed cervical facet dislocations (CFDs); however, to date there has only been one experimental study, using functional spinal units (FSUs), which has systematically produced CFD with concomitant facet fracture. The role of axial compression and distraction on the mechanical response of the cervical facets under intervertebral motions associated with CFD in FSUs has previously been shown. The same has not been demonstrated in multi-segment lower cervical spine specimens under flexion loading (postulated to be the local injury vector associated with CFD). Methods: This study investigated the mechanical response of the bilateral inferior C6 facets of thirteen C5-C7 specimens (67±13 yr, 6 male) during non-destructive constrained flexion, superimposed with each of five axial conditions: (1) 50 N compression (simulating weight of the head); (2-4) 300, 500, and 1000 N compression (simulating the spectrum of intervertebral compression resulting from neck muscle bracing prior to head-first impact and/or externally applied compressive forces); and, (5) 2 mm of C6/C7 distraction (simulating the intervertebral distraction present during inertial loading of the cervical spine by the weight of the head). Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. Results: Increasing amounts of intervertebral compression superimposed on flexion rotations, resulted in increased facet surface strains (range of estimated mean difference relative to Neutral: maximum principal = 77 to 110 µÎµ, minimum principal = 126 to 293 µÎµ, maximum shear = 203 to 375 µÎµ) and angular deflection of the bilateral inferior C6 facets relative to the C6 vertebral body (range of estimated mean difference relative to Neutral = 0.59° to 1.47°). Conclusions: These findings suggest increased facet engagement and higher load transfer through the facet joint, and potentially a higher likelihood of facet fracture under the compressed axial conditions.

The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023.

An Extended Neck Position is Likely to Produce Cervical Spine Injuries Through Buckling in Accidental Head-First Impacts During Rugby Tackling.

Catastrophic cervical spine injuries in rugby often occur during tackling. The underlying mechanisms leading to these injuries remain unclear, with neck hyperflexion and buckling both proposed as the causative factor in the injury prevention literature. The aim of this study was to evaluate the effect of pre-impact head-neck posture on intervertebral neck loads and motions during a head-first rugby tackle. Using a validated, subject-specific musculoskeletal model of a rugby player, and computer simulations driven by in vivo and in vitro data, we examined the dynamic response of the cervical spine under such impact conditions. The simulations demonstrated that the initial head-neck sagittal-plane posture affected intervertebral loads and kinematics, with an extended neck resulting in buckling and supraphysiologic intervertebral shear and flexion loads and motions, typical of bilateral facet dislocation injuries. In contrast, an initially flexed neck increased axial compression forces and flexion angles without exceeding intervertebral physiological limits. These findings provide objective evidence that can inform injury prevention strategies or rugby law changes to improve the safety of the game of rugby.

Kinematics, kinetics, and new insights from a contemporary analysis of the first experiments to produce cervical facet dislocations in the laboratory.

Background: The first experimental study to produce cervical facet dislocation (CFD) in cadaver specimens captured the vertebral motions and axial forces that are important for understanding the injury mechanics. However, these data were not reported in the original manuscript, nor been presented in the limited subsequent studies of experimental CFD. Therefore, the aim of this study was to re-examine the analog data from the first experimental study to determine the local and global spinal motions, and applied axial force, at and preceding CFD. Methods: In the original study, quasistatic axial loading was applied to 14 cervical spines by compressing them between two metal plates. Specimens were fixed caudally via a steel spindle positioned within the spinal canal and a bone pin through the inferior-most vertebral body. Global rotation of the occiput was restricted but its anterior translation was unconstrained. The instant of CFD was identified on sagittal cineradiograph films (N = 10), from which global and intervertebral kinematics were also calculated. Corresponding axial force data (N = 6) were extracted, and peak force and force at the instant of injury were determined. Results: CFD occurred in eight specimens, with an intervertebral flexion angle of 34.8 ± 5.6 degrees, and a 3.1 ± 1.9 mm increase in anterior translation, at the injured level. For seven specimens, CFD was produced at the level of transition from upper neck lordosis to lower neck kyphosis. Five specimens with force data underwent CFD at 545 ± 147 N, preceded by a peak axial force (755 ± 233 N) that appeared to coincide with either fracture or soft tissue failure. Conclusions: Re-examining this rich dataset has provided quantitative evidence that small axial compression forces, combined with anterior eccentricity and upper neck extension, can cause flexion and shear in the lower neck, leading to soft tissue rupture and CFD.

Neck stiffness and range of motion for young males and females.

Well characterised mechanical response of the normal head-neck complex during passive motion is important to inform and verify physical surrogate and computational models of the human neck, and to inform normal baseline for clinical assessments. For 10 male and 10 female participants aged 20 to 29, the range of motion (ROM) of the neck about three anatomical axes was evaluated in active-seated, passive-lying and active-lying configurations, and the neck stiffness was evaluated in passive-lying. Electromyographic signals from the agonist muscles, normalised to maximum voluntary contractions, were used to provide feedback during passive motions. The effect of sex and configuration on ROM, and the effect of sex on linear estimates of stiffness in three regions of the moment-angle curve, were assessed with linear mixed models and generalised linear models. There were no differences in male and female ROM across all motion directions and configurations. Flexion and axial rotation ROM were configuration dependent. The passive-lying moment-angle relationship was typically non-linear, with higher stiffness (slope) closer to end of ROM. When normalising the passive moment-angle curve to active lying ROM, passive stiffness was sex dependent only for lateral bending region 1 and 2. Aggregate moment-angle corridors were similar for males and females in flexion and extension, but exhibited a higher degree of variation in applied moment for males in lateral bending and axial rotation. These data provide the passive response of the neck to low rate bending and axial rotation angular displacement, which may be useful for computational and surrogate modelling of the human neck.

Evaluation of Apparatus and Protocols to Measure Human Passive Neck Stiffness and Range of Motion.

Understanding of human neck stiffness and range of motion (ROM) with minimal neck muscle activation ("passive") is important for clinical and bioengineering applications. The aim of this study was to develop, implement, and evaluate the reliability of methods for assessing passive-lying stiffness and ROM, in six head-neck rotation directions. Six participants completed two assessment sessions. To perform passive-lying tests, the participant's head and torso were strapped to a bending (flexion, extension, lateral bending) or a rotation (axial rotation) apparatus, and clinical bed, respectively. The head and neck were manually rotated by the researcher to the participant's maximum ROM, to assess passive-lying stiffness. Participant-initiated ("active") head ROM was also assessed in the apparatus, and seated. Various measures of apparatus functionality were assessed. ROM was similar for all assessment configurations in each motion direction except flexion. In each direction, passive stiffness generally increased throughout neck rotation. Within-session reliability for stiffness (ICC > 0.656) and ROM (ICC > 0.872) was acceptable, but between-session reliability was low for some motion directions, probably due to intrinsic participant factors, participant-apparatus interaction, and the relatively low participant number. Moment-angle corridors from both assessment sessions were similar, suggesting that with greater sample size, these methods may be suitable for estimating population-level corridors.

Dual DAT and sigma receptor inhibitors attenuate cocaine effects on nucleus accumbens dopamine dynamics in rats.

Psychostimulant use disorders (PSUD) are prevalent; however, no FDA-approved medications have been made available for treatment. Previous studies have shown that dual inhibitors of the dopamine transporter (DAT) and sigma receptors significantly reduce the behavioral/reinforcing effects of cocaine, which have been associated with stimulation of extracellular dopamine (DA) levels resulting from DAT inhibition. Here, we employ microdialysis and fast scan cyclic voltammetry (FSCV) procedures to investigate the effects of dual inhibitors of DAT and sigma receptors in combination with cocaine on nucleus accumbens shell (NAS) DA dynamics in naïve male Sprague Dawley rats. In microdialysis studies, administration of rimcazole (3, 10 mg/kg; i.p.) or its structural analog SH 3-24 (1, 3 mg/kg; i.p.), compounds that are dual inhibitors of DAT and sigma receptors, significantly reduced NAS DA efflux stimulated by increasing doses of cocaine (0.1, 0.3, 1.0 mg/kg; i.v.). Using the same experimental conditions, in FSCV tests, we show that rimcazole pretreatments attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Under the same conditions, JJC8-091, a modafinil analog and dual inhibitor of DAT and sigma receptors, similarly attenuated cocaine-induced stimulation of evoked NAS DA release but produced no additional effect on DA clearance rate. Our results provide the neurochemical groundwork towards understanding actions of dual inhibitors of DAT and sigma receptors on DA dynamics that likely mediate the behavioral effects of psychostimulants like cocaine.

Conspiracy theory beliefs in the adolescent population: A systematic review.

INTRODUCTION: While the study of conspiracy theory beliefs is a relatively new research area, there has been a rise in academic interest in recent years. The literature provides evidence of relationships between conspiracy theory beliefs and a range of factors, but the vast majority of studies are limited to adult samples, and it is unclear how such beliefs present in adolescence. METHODS: The systematic review was conducted according to the PRISMA-S format. Relevant databases were searched up to February 23, 2023, for quantitative studies related to adolescent conspiracy theory beliefs. RESULTS: The six included articles show that conspiracy theory beliefs are present from the start of adolescence, and stable from age 14 upwards, with correlations reported for mistrust and paranoid thinking. Negative relationships were reported for cognitive factors such as ontological confusion, cognitive ability, and actively open-minded thinking. Health-related beliefs correlated with adverse childhood experiences, peer problems, conduct, and sociodemographic factors. Right-wing authoritarianism and anxiety positively correlated with intergroup conspiracy theory beliefs. CONCLUSION: While some factors from adult studies are replicated in the review, there are differences between age groups. The age at which conspiracy theory beliefs begin to form indicate developmental aspects of adolescence, and possibly childhood, that require further examination. Cognitive factors show promise for interventions and should be explored further. However, the lack of studies using adolescent populations is an issue that must be resolved for a greater understanding of conspiracy theory beliefs and a move toward effective interventions.

Treatment of polymyalgia rheumatica: British Society for Rheumatology guideline scope.

The last British Society for Rheumatology (BSR) guideline on PMR was published in 2009. The guideline needs to be updated to provide a summary of the current evidence for pharmacological and non-pharmacological management of adults with PMR. This guideline is aimed at healthcare professionals in the UK who directly care for people with PMR, including general practitioners, rheumatologists, nurses, physiotherapists, occupational therapists, pharmacists, psychologists and other health professionals. It will also be relevant to people living with PMR and organisations that support them in the public and third sector, including charities and informal patient support groups. This guideline will be developed using the methods and processes outlined in the BSR Guidelines Protocol. Here we provide a brief summary of the scope of the guideline update in development.

Building Healthy Babies: A Mixed-Methods Needs Assessment for a Pre-Conception Program in Ontario.

OBJECTIVES: The objective of this study was to gather Ontario clinicians' and public members' views on the design of a pre-conception patient education program. METHODS: In this mixed-methods study, online surveys comprised of rank order, multiple choice, and short answer questions were completed by clinicians and public members. Semi-structured focus groups consisting of 2-6 participants each were then held via videoconference. Demographic variables and survey responses were analyzed quantitatively using descriptive and summary statistics. Descriptive thematic qualitative analysis using the constant comparative method of grounded theory was completed on each transcript to generate themes. RESULTS: A total of 168 public members and 43 clinicians in Ontario completed surveys, while 11 clinicians and 11 public members participated in the focus groups. A pre-conception program in Ontario was felt to be important. An individual appointment with a primary care provider was the favoured program format per survey responses, whereas a virtual format with an interactive component was preferred among focus group participants. Important topics to include were pre-conception health (infertility, genetic screening, folic acid), prenatal and postpartum counselling (diet, activity, substance use, prenatal care, postpartum course), and medical optimization in pregnancy (high-risk medical conditions, medications, mental health). Both groups emphasized the need to consider accommodations for marginalized populations and various cultures and languages. CONCLUSION: A standardized pre-conception patient education program is felt to be of high value by Ontario clinicians and public members. A pre-conception program may help improve obstetrical outcomes and decrease rates of major congenital anomalies in Ontario.

A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women.

Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference - 69%, 95% CI - 127% to - 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.Trial registration: ACTRN12617000545369, registered 18th April 2017.

Bridge improvement work: maximising non-linear optical performance in polyoxometalate derivatives.

New phenyl and stilbene-bridged polyoxometalate (POM) charge-transfer chromophores with diphenylamino donor groups produce, respectively, the highest intrinsic and absolute quadratic hyperpolarisabilities measured for such species. The ß0,zzz obtained for the phenyl bridge - at 180 × 10-30 esu - is remarkable for a short conjugated system while changing to the stilbene (260 × 10-30 esu) produces a substantial increase in non-linearity for a minimal red-shift in the absorption profile. Together with TD-DFT calculations, the results show that maximising conjugation in the π-bridge is vital to high performance in such "POMophores".

Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma.

BACKGROUND: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis. OBJECTIVES: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. METHODS: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. RESULTS: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%. CONCLUSIONS: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.