Studies of Twin Responses to Understand Exercise THerapy (STRUETH): cerebrovascular function.

We studied monozygotic (MZ) and dizygotic (DZ) twin pairs following resistance (RES) and endurance (END) training to assess genetic and environmental contributions to cerebrovascular function. Cerebrovascular function (rest, autoregulation, hypercapnia, exercise) was assessed in 86 healthy same-sex MZ (30 pairs) and DZ (13 pairs) twins, who underwent 3 months of END and RES. Carbon dioxide ( PETCO2${P_{{\rm{ETC}}{{\rm{O}}_{\rm{2}}}}}$ ), mean arterial pressure (MAP) and middle cerebral artery velocity (MCAv) were measured and MCAv resistance (MCACVRi ) was calculated. Resting MCAv reduced by -2.8 cm/s following RES (P = 0.024), with no change following END (-0.3 cm/s, P = 0.758). Change in MCACVRi following RES was +0.11 mmHg/cm/s (P < 0.001), which was significantly greater than END (+0.02 mmHg/cm/s, P = 0.030). MAP also increased following RES (+4 mmHg, P = 0.010), but not END (+1 mmHg, P = 0.518). No changes were apparent in PETCO2${P_{{\rm{ETC}}{{\rm{O}}_{\rm{2}}}}}$ . At rest, positive response rates following RES ranged from 27 to 71% and from 40 to 64% following END. Intraclass correlations between twins were moderate for most variables at baseline. In response to training, only MZ pairs were significantly correlated for a change in MCAv (P = 0.005) and low frequency phase (P = 0.047) following RES.This study is the first to compare cerebrovascular function following RES and END in MZ and DZ twins. Most individuals who did not respond to one modality were able to respond by switching modality, and baseline heritability estimates were higher than training response. Exercise professionals should therefore consider modality and environmental factors when optimising interventions. KEY POINTS: Characterising individual responses to resistance and endurance exercise training can inform optimal strategies for exercise prescription. This study utilised monozygotic and dizygotic twins in a randomised cross-over study to determine individual responsiveness to different modalities of exercise training. The influence of environment vs. genetics on cerebrovascular responses to training was determined. It is apparent that individuals respond differently to distinct exercise stimuli and that switching modality may be a beneficial way to obtain positive responses in cerebrovascular function. This study has implications for improving individualised exercise prescription to maintain or improve cerebrovascular structure and function.

Thoughts of suicide or self-harm among Australian healthcare workers during the COVID-19 pandemic.

OBJECTIVE: To identify the prevalence and predictors of (a) thoughts of suicide or self-harm among healthcare workers during the COVID-19 pandemic and (b) help-seeking among those healthcare workers with thoughts of suicide or self-harm. METHOD: Analysis of data from the Australian COVID-19 Frontline Healthcare Workers Study, an online survey of healthcare workers conducted during the second wave of the COVID-19 pandemic in Australia. Outcomes of interest were thoughts of suicide or self-harm as measured through the Patient Health Questionnaire for depression and help-seeking behaviours. RESULTS: Overall, 819 (10.5%) of 7795 healthcare workers reported thoughts of suicide or self-harm over a 2-week period. Healthcare workers with these thoughts experienced higher rates of depression, anxiety, post-traumatic stress disorder and burnout than their peers. In multivariable models, the odds of suicide or self-harm thoughts were higher among workers who had friends or family infected with COVID-19 (odds ratio = 1.24, 95% confidence interval = [1.06, 1.47]), were living alone (odds ratio = 1.32, 95% confidence interval = [1.06, 1.64]), younger (⩽30 years cf. >50 years; odds ratio = 1.70, 95% confidence interval = 1.36-2.13), male (odds ratio = 1.81, 95% confidence interval = [1.49, 2.20]), had increased alcohol use (odds ratio = 1.58, 95% confidence interval = [1.35, 1.86]), poor physical health (odds ratio = 1.62, 95% confidence interval = [1.36, 1.92]), increased income worries (odds ratio = 1.81, 95% confidence interval = [1.54, 2.12]) or prior mental illness (odds ratio = 3.27, 95% confidence interval = [2.80, 3.82]). Having dependent children was protective (odds ratio = 0.75, 95% confidence interval = [0.61, 0.92]). Fewer than half (388/819) of the healthcare workers who reported thoughts of suicide or self-harm sought professional support. Healthcare workers with thoughts of suicide or self-harm were more likely to seek support if they were younger (⩽30 years cf. >50 years; odds ratio = 1.78, 95% confidence interval = [1.13, 2.82]) or had prior mental health concerns (odds ratio = 4.47, 95% confidence interval = [3.25, 6.14]). CONCLUSION: One in 10 Australian healthcare workers reported thoughts of suicide or self-harm during the pandemic, with certain groups being more vulnerable. Most healthcare workers with thoughts of suicide or self-harm did not seek professional help. Strong and sustained action to protect the safety of healthcare workers, and provide meaningful support, is urgently needed.

Pregnancy and birth characteristics of Aboriginal twins in two Australian states: a data linkage study.

INTRODUCTION: Perinatal outcomes for singleton pregnancies are poorer, on average, for Aboriginal people than non-Aboriginal people, but little is known about Aboriginal multifetal pregnancies. Yet multifetal pregnancies and births are often more complicated and have poorer outcomes than singleton pregnancies. We describe the pregnancies, births and perinatal outcomes for Aboriginal twins born in Western Australia (WA) and New South Wales (NSW) with comparisons to Aboriginal singletons in both states and to non-Aboriginal births in NSW. MATERIALS AND METHODS: Whole-population birth records and birth and death registrations were linked for all births during 2000-2013 (WA) and 2002-2008 (NSW). Hospital records and the WA Register of Developmental Anomalies - Cerebral Palsy were linked for all WA births and hospital records for a subset of NSW births. Descriptive statistics are reported for maternal and child demographics, maternal health, pregnancy complications, births and perinatal outcomes. RESULTS: Thirty-four thousand one hundred twenty-seven WA Aboriginal, 32,352 NSW Aboriginal and 601,233 NSW non-Aboriginal births were included. Pregnancy complications were more common among mothers of Aboriginal twins than Aboriginal singletons (e.g. 17% of mothers of WA twins had hypertension/pre-eclampsia/eclampsia vs 8% of mothers of singletons) but similar to mothers of NSW non-Aboriginal twins. Most Aboriginal twins were born in a principal referral, women's or large public hospital. The hospitals were often far from the mother's home (e.g. 31% of mothers of WA Aboriginal twins gave birth at hospitals located more than 3 h by road from their home). Outcomes were worse for Aboriginal liveborn twins than Aboriginal singletons and non-Aboriginal twins (e.g. 58% of NSW Aboriginal twins were preterm compared to 9% of Aboriginal singletons and 49% non-Aboriginal twins). CONCLUSIONS: Mothers of Aboriginal twins faced significant challenges during the pregnancy, birth and the postnatal period in hospital and, in addition to accessible specialist medical care, these mothers may need extra practical and psychosocial support throughout their journey.

Association of Adult Socioeconomic Status with Body Mass Index: A Within- and Between-Twin Study.

Adult socioeconomic status (SES) has been consistently associated with body mass index (BMI), but it is unclear whether it is linked to BMI independently of childhood SES or other potentially confounding factors. Twin studies can address this issue by implicitly controlling for childhood SES and unmeasured confounders. This co-twin control study used cross-sectional data from Twins Research Australia's Health and Lifestyle Questionnaire (N = 1918 twin pairs). We investigated whether adult SES, as measured by both the Index of Relative Socioeconomic Disadvantage (IRSD) and the Australian Socioeconomic Index 2006 (AUSEI06), was associated with BMI after controlling for factors shared by twins within a pair. The primary analysis was a linear mixed-effects model that estimated effects both within and between pairs. Between pairs, a 10-unit increase in AUSEI06 was associated with a 0.29 kg/m2 decrease in BMI (95% CI [-.42, -.17], p < .001), and a 1-decile increase in IRSD was associated with a 0.26 kg/m2 decrease in BMI (95% CI [-.35, -.17], p < .001). No association was observed within pairs. In conclusion, higher adult SES was associated with lower BMI between pairs, but no association was observed within pairs. Thus, the link between adult SES and BMI may be due to confounding factors common to twins within a pair.

Conducting Clinical Trials in Twin Populations: A Review of Design, Analysis, Recruitment and Ethical Issues for Twin-Only Trials.

Although twins often participate in medical research, few clinical trials are conducted entirely in twin populations. The purpose of this review is to demonstrate the substantial benefits and address the key challenges of conducting clinical trials in twin populations, or 'twin-only trials'. We consider the unique design, analysis, recruitment and ethical issues that arise in such trials. In particular, we describe the different approaches available for randomizing twin pairs, highlight the similarity or correlation that exists between outcomes of twins, and discuss the impact of this correlation on sample size calculations and statistical analysis methods for estimating treatment effects. We also consider the role of both monozygotic and dizygotic twins for studying variation in outcomes, the factors that may affect recruitment of twins, and the ethics of conducting trials entirely in twin populations. The advantages and disadvantages of conducting twin-only trials are also discussed. Finally, we recommend that twin-only trials should be considered more often.

Fitness and strength responses to distinct exercise modes in twins: Studies of Twin Responses to Understand Exercise as a THerapy (STRUETH) study.

KEY POINTS: Exercise is considered medicine; however, the individual degree of responsiveness to a standardized dose of exercise is idiosyncratic. Individual responsiveness between distinct exercise modalities and the genetic/environmental contributions to exercise response are not well understood. In this novel randomized cross-over design study, monozygotic and dizygotic twins, as pairs, underwent 3 months of resistance and endurance training, separated by a 3 month washout period, aiming to assess training responses in strength and fitness outcomes to dichotomous training modalities, as well as the genetic/environmental contributions to exercise response. Our findings indicate that (i) individual responsiveness differs between exercise modalities; (ii) low-responders to one mode may be 'rescued' by switching to an alternate mode of exercise; and (iii) genes may not play as large a role, as previously estimated from cross-sectional data, for exercise training adaptation. The present study has implications for those charged with optimizing the benefits of exercise by means of individualizing the exercise prescription. ABSTRACT: Exercise response is idiosyncratic, although the degree of responsiveness, concordance in response between modalities and genetic contribution to responsiveness are not well understood. We investigated this using a novel randomized cross-over design of dichotomous exercise interventions in mono-(MZ) and di-zygotic (DZ) twin pairs. We studied strength (1RM) and fitness ( V̇O2max ) responses in 84 same-sex untrained twins (30 MZ, 12 DZ pairs; 24.9 ± 5.4 years). Twins, as pairs, underwent 3 months of resistance (RES) and endurance (END) training, separated by a 3 month washout period. Training responses and genetic/environmental contributions to responses were assessed. Leg strength 1RM increased following RES but not END (△47 ± 29 vs. 3 ± 26 kg; P < 0.001), whereas V̇O2max increased following END but not RES (△0.25 ± 0.26 vs. 0.04 ± 0.25 L min-1 ; P < 0.001). A higher percentage of individuals responded to RES for strength and to END for V̇O2max (P < 0.0001). Within-individual responses to each mode were not correlated (P > 0.05). Cross-sectional intraclass correlations were higher for MZ than DZ pairs for all variables, largely as a result of shared environment. Following training, MZ, but not DZ pairs, were significantly correlated for strength change to RES (rMZ = 0.62, P = 0.002) and END (rMZ = 0.36, P = 0.04), and for V̇O2max change to END (L min-1 , rMZ = 0.45, P = 0.02) with a mixture of unshared/shared environmental contributions. Our findings indicate that individual responsiveness differs between modalities and low-responders to one mode may be 'rescued' by switching to an alternate mode. Additionally, genes may not play as large a role as previously estimated from cross-sectional data for training adaptation, and/or cross-sectional data do not reflect longitudinal training effects. The present study has implications for optimizing the individualization of exercise prescription.

Developmental origins of cardiometabolic health outcomes in twins: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies of twins can reduce confounding and provide additional evidence about the causes of disease, due to within-pair matching for measured and unmeasured factors. Although findings from twin studies are typically applicable to the general population, few studies have taken full advantage of the twin design to explore the developmental origins of cardiometabolic health outcomes. We aimed to systematically review the evidence from twin studies and generate pooled estimates for the effects of early-life risk factors on later-life cardiometabolic health. METHODS AND RESULTS: An initial search was conducted in March 2018, with 55 studies of twins included in the review. Risk of bias was assessed using the Newcastle-Ottawa Scale, and eligible studies were included in a meta-analysis, where pooled estimates were calculated. Twenty-six studies analysed twins as individuals, and found that higher birthweight was associated with lower SBP (ß = -2.02 mmHg, 95%CI: -3.07, -0.97), higher BMI (ß = 0.52 kg/m2, 95%CI: 0.20, 0.84) and lower total cholesterol (ß = -0.07 mmol/L, 95%CI: -0.11, -0.04). However, no associations were reported in studies which adjusted for gestational age. Few of the included studies separated their analyses into within-pair and between-pair associations. CONCLUSIONS: Early-life risk factors were associated with cardiometabolic health outcomes in twin studies. However, many estimates from studies in this review were likely to have been confounded by gestational age, and few fully exploited the twin design to assess the developmental origins of cardiometabolic health outcomes.

The Association Between Chronic Disease and Psychological Distress: An Australian Twin Study.

There is a commonly observed association between chronic disease and psychological distress, but many potential factors could confound this association. This study investigated the association using a powerful twin study design that can control for unmeasured confounders that are shared between twins, including genetic and environmental factors. We used twin-paired cross-sectional data from the Adult Health and Lifestyle Questionnaire collected by Twins Research Australia from 2014 to 2017. Linear regression models fitted using maximum likelihood estimations (MLE) were used to test the association between self-reported chronic disease status and psychological distress, measured by the Kessler Psychological Distress Scale (K6). When comparing between twin pairs, having any chronic disease was associated with a 1.29 increase in K6 (95% CI: 0.91, 1.66; p < .001). When comparing twins within a pair, having any chronic disease was associated with a 0.36 increase in K6 (95% CI: 0.002, 0.71; p = .049). This within-pair estimate is of most interest as comparing twins within a pair naturally controls for shared factors such as genes, age and shared lived experiences. Whereas the between-pair estimate does not. The weaker effect found within pairs tells us that genetic and environmental factors shared between twins confounds the relationship between chronic disease and psychological distress. This suggests that associations found in unrelated samples may show exaggerated estimates.

Early birth is a key factor in educational disadvantage of twins: A data linkage study.

AIM: To assess educational outcomes of twins and quantify the degree this is mediated by gestational age and other perinatal factors. METHODS: We conducted a population-based record-linkage cohort study of all live births ≥24 weeks gestation in New South Wales, Australia with a corresponding standardised school test result for grade 3 in 2008-2014. The primary outcome was whether a child met the National Minimum Standard (NMS) cut-off in literacy and numeracy domains. Robust multivariable Poisson models were used to obtain adjusted relative risks (aRRs), and mediation analysis conducted to assess contributing factors on the causal pathway. RESULTS: Of 351 791 liveborn infants, 10 365 (2.9%) were twins. After adjusting for maternal covariates and compared with singletons, twins had an increased risk of not meeting the NMS for all five literacy and numeracy domains (aRR 1.27-1.45, P < .001). Gestational age alone mediated up to 73% of aRRs and small for gestational age further attenuated these effects with only minimal risk remaining after adjusting for all mediators (aRR 0.94-1.07). CONCLUSION: Almost all of the educational disadvantage experienced by twins, compared with singletons, is attributable to the risk associated with shorter gestational age, and partly by poor foetal growth. These findings support efforts to prolong gestation of twin pregnancies.

The Association between Socioeconomic Status and Psychological Distress: A Within and Between Twin Study.

Low socioeconomic status (SES) has been established as a risk factor for poor mental health; however, the relationship between SES and mental health problems can be confounded by genetic and environmental factors in standard regression analyses and observational studies of unrelated individuals. In this study, we used a within-pair twin design to control for unmeasured genetic and environmental confounders in investigating the association between SES and psychological distress. We also employed within-between pair regression analysis to assess whether the association was consistent with causality. SES was measured using the Index of Relative Socio-economic Disadvantage (IRSD), income and the Australian Socioeconomic Index 2006 (AUSEI06); psychological distress was measured using the Kessler 6 Psychological Distress Scale (K6). Data were obtained from Twins Research Australia's Health and Lifestyle Questionnaire (2014-2017), providing a maximum sample size of 1395 pairs. Twins with higher AUSEI06 scores had significantly lower K6 scores than their co-twins after controlling for shared genetic and environmental traits (ßW [within-pair regression coefficient] = -0.012 units, p = .006). Twins with higher income had significantly lower K6 scores than their co-twins after controlling for familial confounders (ßW = -0.182 units, p = .002). There was no evidence of an association between the IRSD and K6 scores within pairs (ßW, p = .6). Using a twin design to eliminate the effect of potential confounders, these findings further support the association between low SES and poor mental health, reinforcing the need to address social determinants of poor mental health, in addition to interventions targeted to individuals.

Twins Research Australia: A New Paradigm for Driving Twin Research.

Twins Research Australia (TRA) is a community of twins and researchers working on health research to benefit everyone, including twins. TRA leads multidisciplinary research through the application of twin and family study designs, with the aim of sustaining long-term twin research that, both now and in the future, gives back to the community. This article summarizes TRA's recent achievements and future directions, including new methodologies addressing causation, linkage to health, economic and educational administrative datasets and to geospatial data to provide insight into health and disease. We also explain how TRA's knowledge translation and exchange activities are key to communicating the impact of twin studies to twins and the wider community. Building researcher capability, providing registry resources and partnering with all key stakeholders, particularly the participants, are important for how TRA is advancing twin research to improve health outcomes for society. TRA provides researchers with open access to its vibrant volunteer membership of twins, higher order multiples (multiples) and families who are willing to consider participation in research. Established four decades ago, this resource facilitates and supports research across multiple stages and a breadth of health domains.

Epigenetic Influences on Neurodevelopment at 11 Years of Age: Protocol for the Longitudinal Peri/Postnatal Epigenetic Twins Study at 11 Years of Age (PETS@11).

Neurodevelopment is sensitive to genetic and pre/postnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri/postnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes; (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological sampling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program - Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.

Is the Association Between Obesity and Hip Osteoarthritis Surgery Explained by Familial Confounding?

BACKGROUND: Familial confounding is confounding due to genetics or environmental exposures shared by family members. We aimed to study whether familial confounding explains the association between body mass index (BMI) and severe hip osteoarthritis (OA). METHODS: We linked data from the Norwegian Arthroplasty Registry with the Norwegian Twin Registry on the National ID-number in 2014, generating a population-based prospective cohort study of same-sex twins born between 1915 and 1960 (53.4% females). BMI was calculated from self-reported height/weight. The outcome was incident hip arthroplasty due to OA (follow-up time, 1987-2014; 424 914 person-years). We performed sex-specific co-twin control analyses of dizygotic (N = 5,226) and monozygotic (MZ, N = 3,803) twin pairs using Cox regression models and explored reasons for any familial confounding using bivariate twin models. RESULTS: The mean (SD) BMI was 22.6 (2.96), peak lifetime BMI 25.6 (2.61), and N = 614 had hip surgery due to OA. In cohort analyses, BMI was associated with hip OA for women and men (hazard ratio [HR] = 1.09, 95% confidence intervals [CIs] = 1.06 to 1.11 and HR = 1.08, 95% CI = 1.04 to 1.12, respectively). When adjusting for familial confounding within MZ twins, the association got stronger for women (HR = 1.19; 95% CI = 1.05 to 1.36) but weaker for men (HR = 0.93; 95% CI = 0.75 to 1.16). There was no genetic overlap between BMI and hip OA, yet the familial confounding in men provides suggestive evidence that the association could be explained by shared environmental factors. CONCLUSION: The association between BMI and hip OA may be explained by familial confounding for men. For women, there was no evidence for familial confounding, consistent with a causal association. See video abstract at, http://links.lww.com/EDE/B336.

Socioeconomic position in young adulthood is associated with BMI in Australian families.

BACKGROUND: Low socioeconomic position (SEP) is associated with increased cardiovascular (CV) disease risk, but the relative importance of SEP in childhood and adulthood, and of changes in SEP between these two life stages, remains unclear. Studies of families may help clarify these issues. We aimed to assess whether SEP in young adulthood, or change in SEP from childhood to young adulthood, was associated with five continuously measured CV risk factors. METHODS: We used data from 286 adult Australian families from the Victorian Family Heart Study (VFHS), in which some offspring have left home (n = 364) and some remained at home (n = 199). SEP (defined as the Index of Relative Socioeconomic Disadvantage) was matched to addresses. We fitted variance components models to test whether young adult SEP and/or change in SEP was associated with systolic blood pressure, diastolic blood pressure, body mass index (BMI), total cholesterol or high-density lipoprotein cholesterol, after adjustment for parental SEP and within-family correlation. RESULTS: An increase in SEP of 100 SEIFA units from childhood to adulthood was associated with a lower BMI (ß = -0.49 kg/m(2), P < 0.01) only. CONCLUSIONS: These results suggest that a change in SEP in young adulthood is an important predictor of BMI, independent of childhood SEP.

Non-proportional odds multivariate logistic regression of ordinal family data.

Methods to examine whether genetic and/or environmental sources can account for the residual variation in ordinal family data usually assume proportional odds. However, standard software to fit the non-proportional odds model to ordinal family data is limited because the correlation structure of family data is more complex than for other types of clustered data. To perform these analyses we propose the non-proportional odds multivariate logistic regression model and take a simulation-based approach to model fitting using Markov chain Monte Carlo methods, such as partially collapsed Gibbs sampling and the Metropolis algorithm. We applied the proposed methodology to male pattern baldness data from the Victorian Family Heart Study.

Exploring the Association Between Help-Seeking Intentions and Suicidal Ideation in Australian Adult Men.

Background: Men account for three-quarters of suicide deaths in Australia. Self-reliant masculine norms may act as barriers to men's help-seeking and contribute to suicidal ideation. Men who seek help may be less likely to experience suicidal ideation. Aim: We evaluated the association between help-seeking intentions and suicidal ideation in Australian adult men using data from Wave 2 of the Australian Longitudinal Study on Male Health (Ten to Men). Method: Using scores on the General Help-Seeking Questionnaire, we explored the association between informal help-seeking intentions (e.g., friend, family), formal help-seeking intentions (e.g., psychologist), overall help-seeking intentions (all sources), and new-onset suicidal ideation. We conducted logistic regression analyses using a sample of 7,828 men aged 18-60 years. Results: Increased overall help-seeking intentions and informal help-seeking intentions were significantly associated with lower odds of new-onset suicidal ideation, whereas formal help-seeking intentions were not significantly associated. Limitations: The cross-sectional design limits inferences about causality. Conclusion: Men who have greater informal help-seeking intentions may be less likely to experience a new onset of suicidal ideation; however, more longitudinal research is needed.

Computed tomography scan radiation and brain cancer incidence.

BACKGROUND: Computed tomography (CT) scans make substantial contributions to low-dose ionizing radiation exposures, raising concerns about excess cancers caused by diagnostic radiation. METHODS: Deidentified medicare records for all Australians aged 0-19 years between 1985-2005 were linked to national death and cancer registrations to 2012. The National Cancer Institute CT program was used to estimate radiation doses to the brain from CT exposures in 1985-2005, Poisson regression was used to model the dependence of brain cancer incidence on brain radiation dose, which lagged by 2 years to minimize reverse causation bias. RESULTS: Of 10 524 842 young Australians, 611 544 were CT-exposed before the age of 20 years, with a mean cumulative brain dose of 44 milligrays (mGy) at an average follow-up of 13.5 years after the 2-year lag period. 4472 were diagnosed with brain cancer, of whom only 237 had been CT-exposed. Brain cancer incidence increased with radiation dose to the brain, with an excess relative risk of 0.8 (95% CI 0.57-1.06) per 100 mGy. Approximately 6391 (95% CI 5255, 8155) persons would need to be exposed to cause 1 extra brain cancer. CONCLUSIONS: For brain tumors that follow CT exposures in childhood by more than 2 years, we estimate that 40% (95% CI 29%-50%) are attributable to CT Radiation and not due to reverse causation. However, because of relatively low rates of CT exposure in Australia, only 3.7% (95% CI 2.3%-5.4%) of all brain cancers are attributable to CT scans. The population-attributable fraction will be greater in countries with higher rates of pediatric scanning.

Exercise and Artery Function in Twins: Sex Differences in a Cross-Over Trial.

BACKGROUND: Physical activity reduces cardiovascular risk, partly via direct effects on the arterial wall. We hypothesized that vascular function responses would be modality-specific, sex-dependent, and express a high degree of heritability. METHODS: We recruited 90 same-sex twins (31 monozygotic, 14 dizygotic dizygotic pairs; 25.8±6.0 years) and randomized 70 (25 monozygotic, 10 dizygotic) to complete, as pairs, 3 months each of resistance and endurance training, separated by a 3-month washout. RESULTS: Brachial artery flow-mediated (FMD%) and glyceryl-trinitrate induced dilation (GTN%) both increased following endurance (FMD%: ∆1.46%, P<0.001; GTN%: ∆1.76%, P=0.004) and resistance (FMD%: ∆1.73%, P<0.001; GTN%: ∆1.68%, P=0.045). About one-third of participants failed to respond to one or other mode; 10% failed to respond to both for FMD% (17% for GTN%). FMD% and GTN% increased significantly in response to both resistance and endurance in females (P<0.05), but not males. Twin analysis revealed that responses to both FMD% and GTN% with exercise training for both modalities were dependent on factors shared by monozygotic pairs and that a large contribution from genetic effects is unlikely. CONCLUSIONS: Our findings indicate that both endurance and resistance can enhance vascular function and that responses in females were more marked. Most individuals respond to one or other form of training, with few unresponsive to both; a finding that has implications for optimizing exercise-based approaches for individualized benefit. Focusing on characteristics of exercise prescription may be more important than the impact of distinct candidate genes when considering exercise as a form of vascular medicine. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371222; Unique identifier: ACTRN 12616001095459.

Evaluating the Effectiveness of Components of National Suicide Prevention Strategies.

Background: National suicide prevention strategies support development of suicide prevention activities and their evaluation. Aims: To describe components included in national suicide prevention strategies and analyze the potential contribution of individual components to reduce suicide rates. Method: We conducted a narrative review and statistical analysis of national suicide prevention strategies. The narrative review was based on a framework of 12 components and included 29 countries (14 lower middle-income countries [LMICs] and 15 high-income countries [HICs]) with a national suicide prevention strategy. The statistical analyses covered suicide mortality data for 24 countries with a national strategy (9 LMICs and 15 HICs). Results: The number of components adopted in national strategies ranged from 4 to 11, and training and education were included in 96.5% of strategies. Estimated period effects for total suicide rates in individual countries ranged from a significant decrease in the yearly suicide rate (RR = 0.80; 95% CI 0.69-0.93) to a significant increase (RR = 1.12; 95% CI 1.05-1.19). There were no changes in suicide mortality associated with individual components of national strategies. Limitations: The limitations of existing suicide mortality data apply to our study. Conclusion: Further detailed evaluations will help identify the specific contribution of individual components to the impact national strategies. Until then, countries should be encouraged to implement and evaluate comprehensive national suicide prevention strategies.