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Objective: Child and adult body mass index (BMI) associates with adult carotid artery intima-media thickness (cIMT). However, the relative contribution of BMI at different life-periods on adult cIMT has not been quantified. This study aimed to determine the life-course model that best explains the relative contribution of BMI at different life-periods (childhood, adolescence, and young-adulthood) on cIMT in adulthood., Methods: BMI was calculated from direct measurements of height and weight at up to seven time-points from childhood to adulthood (1973-2007) among 2485 participants of the Cardiovascular Risk in Young Finns Study (YFS) and 1271 participants in the Bogalusa Heart Study (BHS). BMI measures at three ages representative of childhood (9-years), adolescence (18 years) and young-adulthood (30 years) life-periods were used. B-mode ultrasound was used to measure common cIMT in adulthood (>30 years). Associations were evaluated using the Bayesian relative life-course exposure model., Results: In both cohorts, cumulative exposure to higher levels of BMI across the life-course was associated with greater cIMT. Of the examined life-periods, BMI in young-adulthood provided the greatest relative contribution towards the development of adult cIMT for YFS (49.9 %, 95 % CrI = 34-68 %) and white BHS participants (48.6 %, 95 % CrI = 9-86 %), whereas BMI in childhood had the greatest relative contribution for black BHS participants (54.0 %, 95 % CrI = 8-89 %)., Conclusion: Although our data suggest sensitive periods in the life-course where prevention and intervention aimed at reducing BMI might provide most benefit in limiting the effects of BMI on cIMT, maintaining lower BMI across the life-course appears to be optimal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Transport-related physical activity levels differ across the lifecourse; however, the nature of these differences is poorly understood. This study examined the relationship between correlates of transport-related physical activity and how they differ in strength, pathway, and direction across the lifecourse. Structural Equation Modelling assessed relationships between correlates (e.g., age, smoking, education) and transport-related physical activity (assessed via the International Physical Activity Questionnaire) at four timepoints of the Australian Childhood Determinants of Adult Health study: childhood (7-15y; n = 6302), early-adulthood (26-36y; n = 2700), early/mid-adulthood (31-41y; n = 1649), and mid-adulthood (36-49y; n = 1794). Several pathways were consistent across the lifecourse. Self-rated health directly associated with transport-related physical activity across all timepoints. During adulthood greater body mass index and smoking frequency were indirectly associated with lower levels of transport-related physical activity via self-rated health; similarly, lower educated adults, who smoked more frequently, and had poorer health, had lower transport-related physical activity. Urban residence was directly associated with greater transport-related physical activity in childhood and early-adulthood; having more children in early/mid- and mid-adulthood was directly associated with less transport-related physical activity. This is the first study to report pathways of direct and indirect association between correlates and transport-related physical activity at key lifecourse stages. The pathways highlighted can inform policy and practice to aid in the development of age-specific lifecourse interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Although cardiovascular disease (CVD) begins in early life, the extent to which blood pressure (BP) at different life stages contributes to CVD is unclear., Objective: To determine the relative contribution of BP at different life stages across the early-life course from infancy to young adulthood with carotid intima-media thickness (IMT)., Design, Setting, and Participants: The analyses were performed in 2022 using data gathered from July 1989 through January 2018 within the Special Turku Coronary Risk Factor Intervention Project, a randomized, infancy-onset cohort of 534 participants coupled with annual BP (from age 7 months to 20 years), biennial IMT measurements (from ages 13 to 19 years), who were followed up with again at age 26 years., Exposures: BP measured from infancy (aged 7 to 13 months), preschool (2 to 5 years), childhood (6 to 12 years), adolescence (13 to 17 years), and young adulthood (18 to 26 years)., Main Outcomes and Measures: Primary outcomes were carotid IMT measured in young adulthood at age 26 years. Bayesian relevant life-course exposure models assessed the relative contribution of BP at each life stage., Results: Systolic BP at each life stage contributed to the association with young adulthood carotid IMT (infancy: relative weight, 25.3%; 95% credible interval [CrI], 3.6-45.8; preschool childhood: relative weight, 27.0%; 95% CrI, 3.3-57.1; childhood: relative weight, 18.0%; 95% CrI, 0.5-40.0; adolescence: relative weight, 13.5%; 95% CrI, 0.4-37.1; and young adulthood: relative weight, 16.2%; 95% CrI, 1.6-46.1). A 1-SD (at single life-stage) higher systolic BP accumulated across the life course was associated with a higher carotid IMT (0.02 mm; 95% CrI, 0.01-0.03). The findings for carotid IMT were replicated in the Cardiovascular Risk in Young Finns Study that assessed systolic BP from childhood and carotid IMT in adulthood (33 to 45 years)., Conclusion and Relevance: In this cohort study, a life-course approach indicated that accumulation of risk exposure to BP levels at all life stages contributed to adulthood carotid IMT. Of those, the contribution attributed to each observed life stage was approximately equal. These results support prevention efforts that achieve and maintain normal BP levels across the life course, starting in infancy.

Background and Aims: It is unclear why blood pressure (BP), metabolic markers and smoking increase stroke incidence in women more than men. We examined these associations with carotid artery structure and function in a prospective cohort study., Methods: Participants in the Australian Childhood Determinants of Adult Health study at ages 26-36 years (2004-06) were followed-up at 39-49 years (2014-19). Baseline risk factors included smoking, fasting glucose, insulin, systolic and diastolic BP. Carotid artery plaques, intima-media thickness [IMT], lumen diameter and carotid distensibility [CD] were assessed at follow up. Log binomial and linear regression with risk factor × sex interactions predicted carotid measures. Sex-stratified models adjusting for confounders were fitted when significant interactions were identified., Results: Among 779 participants (50% women), there were significant risk factor × sex interactions with baseline smoking, systolic BP and glucose associated with carotid measures in women only. Current smoking was associated with incidence of plaques (RR unadjusted 1.97 95% CI 1.4, 3.39), which reduced when adjusted for sociodemographics, depression, and diet (RR adjusted 1.82 95% CI 0.90, 3.66). Greater systolic BP was associated with lower CD adjusted for sociodemographics (β adjusted -0.166 95% CI -0.233, -0.098) and hypertension with greater lumen diameter (β unadjusted 0.131 95% CI 0.037, 0.225), which decreased when adjusted for sociodemographics, body composition and insulin (β adjusted 0.063 95% CI -0.052, 0.178). Greater glucose (β unadjusted -0.212 95% CI -0.397, -0.028) was associated with lower CD, which decreased when adjusted for sociodemographics, BP, depression and polycystic ovary syndrome (β adjusted -0.023 95% CI -0.249, 0.201)., Conclusions: Smoking, SBP and glucose affect carotid structure and function more in women than men with some of this risk due to co-occurring risk factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We examined area-level (aSES) and individual-level (iSES) socio-economic status on trajectories of HRQoL to 10 years following stroke., Methods: Participants with strokes between 1/5/1996 and 30/4/1999 completed the Assessment of Quality of Life instrument (AQoL, range: -0.04 [worse than death] to 0 [death] to 1 [full health]) at ≥one of 3month, 6-month, 1-year, 2-year, 3-year, 4-year, 5-year, 7-year and 10-year interviews after stroke. Sociodemographic and health information were collected at baseline. We derived aSES from postcode using the Australian Socio-Economic Indexes For Area (2006) (categories: high, medium, low), and iSES from lifetime occupation (categories: non-manual, manual). Multivariable linear mixed effects modelling was used to estimate trajectories of HRQoL over 10 years, by aSES and iSES, adjusting for age, sex, cardiovascular disease, smoking, diabetes, stroke severity, stroke type, and the time influence on age and health conditions., Results: Of 1,686 participants enrolled, we excluded 239 with 'possible' stroke and 284 with missing iSES. Among the remaining 1,163 participants, 1,123 (96.6%) had AQoL assessed at ≥3 timepoints. In multivariable analysis, over time, people in the medium aSES group had mean 0.02 (95% CI -0.06, 0.02) greater reduction in AQoL score, and people in the low aSES group had mean 0.04 (95% CI, -0.07, -0.001) greater reduction, than those in the high aSES group. Manual workers had an average 0.04 (95% CI, -0.07, -0.01) greater reduction in AQoL score over time than non-manual workers., Conclusions: Over time, HRQoL declines in all people with stroke, declining most rapidly in lower SES groups., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Transport-related physical activity (TRPA) is recognised as a potential means of increasing total physical activity participation that may yield substantial health benefits. Public health campaigns focusing on promoting TRPA from a young age aim to develop life-long healthy habits. However, few studies have examined how TRPA changes across the lifecourse and whether childhood TRPA levels influence those observed later in life., Methods: Using the Australian Childhood Determinants of Adult Health study (baseline, 1985), latent class growth mixture modelling with adjustment for time-varying covariates was performed using four timepoints (ranging from 7 to 49 years) to assess behavioural patterns and retention of TRPA across the lifecourse. As child and adult adjusted TRPA measures could not be harmonised, trajectories of adult TRPA (n = 702) were instead identified, and log-binomial regression analysis was performed to determine whether childhood levels of TRPA (high/medium/low) influenced these trajectories., Results: Two stable groups of adult TRPA trajectories were identified: persistently low (n = 520; 74.2%), and increasingly high TRPA (n = 181; 25.8%). There was no significant relationship between childhood TRPA levels and patterns in adulthood (relative risk of high childhood TRPA yielding high adult TRPA trajectory membership = 1.06; 95% confidence interval = 0.95-1.09)., Conclusion: This study found childhood TRPA levels were not associated with TRPA patterns in adulthood. These findings suggest that while TRPA in childhood may have health, social, and environmental benefits, it does not appear to impact adult TRPA directly. Therefore, further intervention is required beyond childhood to promote the implementation of healthy TRPA behaviours into adulthood., (© 2023. The Author(s).)

AbstractUnifying models have shown that the amount of space used by animals (e.g., activity space, home range) scales allometrically with body mass for terrestrial taxa; however, such relationships are far less clear for marine species. We compiled movement data from 1,596 individuals across 79 taxa collected using a continental passive acoustic telemetry network of acoustic receivers to assess allometric scaling of activity space. We found that ectothermic marine taxa do exhibit allometric scaling for activity space, with an overall scaling exponent of 0.64. However, body mass alone explained only 35% of the variation, with the remaining variation best explained by trophic position for teleosts and latitude for sharks, rays, and marine reptiles. Taxon-specific allometric relationships highlighted weaker scaling exponents among teleost fish species (0.07) than sharks (0.96), rays (0.55), and marine reptiles (0.57). The allometric scaling relationship and scaling exponents for the marine taxonomic groups examined were lower than those reported from studies that had collated both marine and terrestrial species data derived using various tracking methods. We propose that these disparities arise because previous work integrated summarized data across many studies that used differing methods for collecting and quantifying activity space, introducing considerable uncertainty into slope estimates. Our findings highlight the benefit of using large-scale, coordinated animal biotelemetry networks to address cross-taxa evolutionary and ecological questions.

Introduction: Smokers can respond defensively to health risk communication such as on-pack warning labels, potentially reducing their effectiveness. Theory suggests that risk perception together with self-efficacy reduces defensive responses and predicts target behaviors. Currently, tobacco warning labels globally predominantly target risk and do not explicitly consider efficacy., Aims: This study explores the effectiveness of combining Australian tobacco warning labels with efficacy content to increase quitting intentions., Methods: RCT in 83 smokers over 3 weeks. After a seven-day baseline phase (smoking from usual tobacco packaging), participants were randomized to one of two adhesive labels groups for the remaining 14 days: Standard health warning labels (HWLs) featuring enhanced efficacy messages (experimental group) or unmodified standard HWLs (control group). Participants attached these labels to their tobacco packaging and recorded their cognitions and smoking behavior once daily using Smartphones. Multilevel structural equation modeling was used to test theorized effects of the labels on self-efficacy, risk perception, and intentions to quit., Results: There was no effect of exposure to efficacy messages on either self-efficacy, risk perceptions, or intentions to quit. However, self-efficacy and risk perceptions were positively associated with quitting intentions at the within-person level., Conclusions: The predictive relationships between self-efficacy, risk perception, and intention to quit were supported, however, supplementing standard warning labels with efficacy messages had no effect on these cognitions. Whether this is due to conditioned avoidance of HWLS, characteristics of the messages, or limitations imposed by format are unclear., Implications: Self-efficacy and risk perception predict intentions to quit smoking. Adding efficacy content to tobacco health warnings may have the potential to bolster these cognitions but more research is required to determine the contexts in which this would be effective and who would be likely to benefit. The time course by which exposure to efficacy content might influence cessation self-efficacy and downstream quitting intentions also needs to be investigated., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background The origins of sex differences in cardiovascular diseases are not well understood. We examined the contribution of childhood risk factors to sex differences in adult carotid artery plaques and intima-media thickness (carotid IMT). Methods and Results Children in the 1985 Australian Schools Health and Fitness Survey were followed up when they were aged 36 to 49 years (2014-19, n=1085-1281). Log binomial and linear regression examined sex differences in adult carotid plaques (n=1089) or carotid IMT (n=1283). Childhood sociodemographic, psychosocial, and biomedical risk factors that might contribute to sex differences in carotid IMT/plaques were examined using purposeful model building with additional adjustment for equivalent adult risk factors in sensitivity analyses. Women less often had carotid plaques (10%) than men (17%). The sex difference in the prevalence of plaques (relative risk [RR] unadjusted 0.59 [95% CI, 0.43 to 0.80]) was reduced by adjustment for childhood school achievement and systolic blood pressure (RR adjusted 0.65 [95% CI, 0.47 to 0.90]). Additional adjustment for adult education and systolic blood pressure further reduced sex difference (RR adjusted 0.72 [95% CI, 0.49 to 1.06]). Women (mean±SD 0.61±0.07) had thinner carotid IMT than men (mean±SD 0.66±0.09). The sex difference in carotid IMT (β unadjusted -0.051 [95% CI, -0.061 to -0.042]) reduced with adjustment for childhood waist circumference and systolic blood pressure (β adjusted -0.047 [95% CI, -0.057 to -0.037]) and further reduced with adjustment for adult waist circumference and systolic blood pressure (β adjusted -0.034 [95% CI, -0.048 to -0.019]). Conclusions Some childhood factors contributed to adult sex differences in plaques and carotid IMT. Prevention strategies across the life course are important to reduce adult sex differences in cardiovascular diseases.

Aims: Most international guidelines recommend that repeat blood pressure (BP) readings are required for BP classification. Two international guidelines diverge from this by recommending that no further BP measurements are required if the first clinic BP is below a hypertension threshold. The extent to which within-visit BP variability patterns change over time, and whether this could impact BP classification is unknown. We sought to examine this., Methods and Results: Data were from the Cardiovascular Risk in Young Finns Study, a prospective cohort study. Up to 2799 participants were followed from childhood (9-15 years) to adulthood (18-49 years) over up to six visits. Patterns of within-visit systolic BP (SBP) variability were defined as no-change, decrease, increase between consecutive readings (with 5 mmHg change thresholds). Classification of SBP (normal, high-normal, hypertension) using the first reading was compared with repeat readings. On average, SBP decreased with subsequent measures, but with major individual variability (no-change: 56.9-62.7%; decrease: 24.1-31.6%; increase: 11.5-16.8%). Patterns of SBP variability were broadly similar from childhood to adulthood, with the highest prevalence of an increase among participants categorized with normal SBP (12.6-20.3%). The highest prevalence of SBP reclassification occurred among participants with hypertension (28.9-45.3% reclassified as normal or high-normal). The prevalence of reclassification increased with the magnitude of change between readings., Conclusion: There is a major individual variation of within-visit SBP change in childhood and adulthood and can influence BP classification. This highlights the importance of consistency among guidelines recommending that repeat BP measurements are needed for BP classification., Competing Interests: Conflict of interest: No support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: To promote greater muscular strength across the life course and, in turn, help improve long-term health outcomes, strategies aimed at increasing muscular strength are required. To inform these strategies, this study identified childhood factors associated with muscular strength trajectories., Methods: Prospective longitudinal study of 1280 Childhood Determinants of Adult Health participants who had a range of potentially modifiable factors (e.g., anthropometric measures, physical activity) and health and risk motivation items (e.g., attitudes, beliefs, and intentions on health-related actions) measured in childhood and had their muscular strength assessed up to three times between childhood and midlife. Associations between childhood factors and three predetermined life course muscular strength trajectories (identified previously using group-base trajectory modeling as follows: above average and increasing, average, and below average and decreasing) were examined using log multinomial regression., Results: Greater physical fitness, physical activity, fat-free mass, enjoyment of physical activity, physical education, and school sports, and positive attitudes regarding the importance of exercising, staying fit, and body image were associated with a lower likelihood of being in the below average and decreasing muscular strength trajectory (relative risk range, 0.45-0.98). Greater physical fitness, physical activity, and fat-free mass, and attending an independent school were associated with a higher likelihood of being in the above average and increasing muscular strength trajectory (relative risk range, 1.03-1.93)., Conclusions: In addition to providing health benefits in the short term, physical activity, physical fitness, positive health attitudes, and healthy weight in childhood may lead to better muscular strength in the long term., (Copyright © 2022 by the American College of Sports Medicine.)

Introduction: Transport-related physical activity (TRPA) has been identified as a way to increase physical activity due to its discretionary and habitual nature. Factors thought to influence TRPA span multiple disciplines and are rarely systematically considered in unison. This systematic review aimed to identify cross-sectional and longitudinal factors associated with adult TRPA across multiple research disciplines., Methods: Using four electronic databases, a systematic search of English, peer-reviewed literature from 2010 - 2020 was performed. Studies quantitatively examining factors associated with the outcome of adult TRPA were eligible., Results: Seventy-three studies (n = 66 cross-sectional; n = 7 longitudinal) were included, cumulatively reporting data from 1,278,632 observations. Thirty-six factors were examined for potential association with TRPA and presented in a social-ecological framework: individual (n = 15), social (n = 3), and environmental (n = 18). Seven factors were found to be consistently associated with higher adult TRPA: lower socio-economic status, higher self-efficacy, higher social normalization, lower distance of travel, higher destination concentration, more streetlighting, and higher public transportation frequency with a greater number of terminals near route start and endpoints., Conclusions: This is the first comprehensive compilation of the correlates and determinants of adult TRPA. Seven individual, social, and environmental factors demonstrated consistent associations with TRPA. Models formed using these factors may facilitate more effective promotion of TRPA. There is a lack of longitudinal studies as well as studies assessing cognitive/attitudinal and social factors, highlighting gaps for further research. Those developing policies and strategies targeting TRPA need to consider a range of factors at the individual, social, and environmental level to maximise the likelihood of effectiveness., (© 2022. The Author(s).)

Background Blood pressure associates with arterial stiffness, but the contribution of blood pressure at different life stages is unclear. We examined the relative contribution of childhood, young- and mid-adulthood blood pressure to mid-adulthood large artery stiffness. Methods and Results The sample comprised 1869 participants from the Cardiovascular Risk in Young Finns Study who had blood pressure measured in childhood (6-18 years), young-adulthood (21-30 years), and mid-adulthood (33-45 years). Markers of large artery stiffness were pulse wave velocity and carotid distensibility recorded in mid-adulthood. Bayesian relevant life course exposure models were used. For each 10-mm Hg higher cumulative systolic blood pressure across the life stages, pulse wave velocity was 0.56 m/s higher (95% credible interval: 0.49 to 0.63) and carotid distensibility was 0.13%/10 mm Hg lower (95% credible interval: -0.16 to -0.10). Of these total contributions, the highest contribution was attributed to mid-adulthood systolic blood pressure (relative weights: pulse wave velocity, childhood: 2.6%, young-adulthood: 5.4%, mid-adulthood: 92.0%; carotid distensibility, childhood: 5.6%; young-adulthood: 10.1%; mid-adulthood: 84.3%), with the greatest individual contribution coming from systolic blood pressure at the time point when pulse wave velocity and carotid distensibility were measured. The results were consistent for diastolic blood pressure, mean arterial pressure, and pulse pressure. Conclusions Although mid-adulthood blood pressure contributed most to mid-adulthood large artery stiffness, we observed small contributions from childhood and young-adulthood blood pressure. These findings suggest that the burden posed by arterial stiffness might be reduced by maintaining normal blood pressure levels at each life stage, with mid-adulthood a critical period for controlling blood pressure.

Background: Understanding lifecourse trajectories of body-mass index (BMI) is important for identifying groups at high risk of poor health and potential target points for intervention. This study aimed to describe BMI trajectories from childhood to mid-adulthood in four population-based cohorts established in the 1970s and 1980s and to identify childhood sociodemographic factors related to trajectory membership., Methods: Between Dec 17, 1970 and Dec 15, 1994, data were collected at the first visit from 9830 participants from the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes participants from Australia (1985), Finland (1980) and the USA (1970-1994). Participants had at least three measures of height and weight, including one in childhood (6-18 years) and one in adulthood (>18 years), and were aged 30-49 years at last measurement. Latent Class Growth Mixture Modelling was used to identify lifecourse BMI trajectory groups and log multinomial regression models were fit to identify their childhood sociodemographic predictors., Findings: Five consistent BMI trajectory groups were identified amongst the four cohorts: persistently low (35.9-58.6%), improving from high (0.7-4.8%), progressing to moderate (9.3-43.7%), progressing to high (1.1-6.0%), and progressing to very high (0.7-1.3%). An additional three BMI trajectory groups were identified in some, but not all, cohorts: adult onset high (three cohorts; 1.8-20.7%), progressing to moderate-high (two cohorts; 5.2-13.8%), and relapsing yo-yoers (alternating upward and downward; one cohort; 1.3%). In pooled analyses, each predictor variable in childhood, including age, gender, parental education and race, was associated with increased likelihood of belonging to the most (e.g., improving from high) and least (e.g., progressing to very high) favourable BMI trajectory groups, suggesting a U-shaped (or inverse U-shaped) pattern of association., Interpretation: Five consistent BMI trajectory groups were identified across four cohorts from Australia, Finland, and the USA, mainly across two eras of birth. While most participants remained on a persistently low trajectory (50%), many demonstrated worsening BMI trajectories (47%), with only few demonstrating improving trajectories (<5%). Age, gender, parental education, and race appear to be important predictors of BMI trajectory group membership and need consideration in preventive and management strategies., Funding: This study was supported by funding from the National Institutes of Health, National Heart, Lung and Blood Institute (grant number R01 HL121230)., Competing Interests: We declare no competing interests., (© 2022 The Author(s).)

Background and Aims: Low muscular strength associates with the metabolic syndrome (MetS). However, how muscular strength measured at different life stages contribute to the development of MetS is unknown. This study compared the contribution of muscular strength measured in youth, young- and mid-adulthood with MetS in midlife., Methods and Results: Prospective longitudinal study of 267 Childhood Determinants of Adult Health Study participants who between 1985 and 2019 had measures of muscular strength (dominant grip strength) at three life stages (youth = 9-15 years, young adulthood = 26-36 years, mid-adulthood = 36-49 years) and had their MetS status assessed in mid-adulthood. Bayesian relevant life-course exposure models quantified associations between muscular strength at each life stage with MetS and estimated the maximum accumulated effect of lifelong muscular strength. The contribution of muscular strength at each life stage with MetS was equal (youth = 38%, young adulthood = 28%, mid-adulthood = 34%). A one standard deviation increase in cumulative muscular strength was associated with 46% reduced odds of MetS. Of all MetS components, muscular strength was most strongly negatively associated with high waist circumference., Conclusion: A life-course approach demonstrated reduced odds of MetS in midlife was associated with cumulatively high muscular strength since youth. This supports efforts to promote physical fitness throughout life., Competing Interests: Declaration of competing interest Funding bodies and sponsors did not play a role in the study design, collection, analysis, or interpretation of data, in the writing of the manuscript, or the decision to submit the manuscript for publication. The authors declare no conflict of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Importance: Rapid access to specialized care is recommended to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH), but understanding of the optimal onset-to-treatment time for aneurysmal SAH is limited., Objective: To assess the optimal onset-to-treatment time for aneurysmal SAH that maximized patient outcomes after surgery., Design, Setting, and Participants: This cohort study assessed 575 retrospectively identified cases of first-ever aneurysmal SAH occurring within the referral networks of 2 major tertiary Australian hospitals from January 1, 2010, to December 31, 2016. Individual factors, prehospital factors, and hospital factors were extracted from the digital medical records of eligible cases. Data analysis was performed from March 1, 2020, to August 31, 2021., Exposures: Main exposure was onset-to-treatment time (time between symptom onset and aneurysm surgical treatment in hours) derived from medical records., Main Outcomes and Measures: Clinical characteristics, complications, and discharge destination were extracted from medical records and 12-month survival obtained from data linkage. The associations of onset-to-treatment time (in hours) with (1) discharge destination of survivors (home vs rehabilitation), (2) 12-month survival, and (3) neurologic complications (rebleed, delayed cerebral ischemia, meningitis, seizure, hydrocephalus, and delayed cerebral injury) were investigated using natural cubic splines in multivariable Cox proportional hazards and logistic regression models., Results: Of the 575 patients with aneurysmal SAH, 482 patients (mean [SD] age, 55.0 [14.5] years; 337 [69.9%] female) who received endovascular coiling or neurosurgical clipping were studied. A nonlinear association of treatment delay was found with the odds of being discharged home vs rehabilitation (effective df = 3.83 in the generalized additive model, χ2 test P = .002 for the 4-df cubic spline), with a similar nonlinear association remaining significant after adjustment for sex, treatment modality, severity, Charlson Comorbidity Index, history of hypertension, and hospital transfer (likelihood ratio test: df = 3, deviance = 9.57, χ2 test P = .02). Both unadjusted and adjusted cox regression models showed a nonlinear association between time to treatment and 12-month mortality with the lowest hazard of death with receipt of treatment at 12.5 hours after symptom onset, although the nonlinear term became nonsignificant upon adjustment. The odds of being discharged home were higher with treatment before 20 hours after onset, with the probability of being discharged home compared with rehabilitation or other hospital increased by approximately 10% when treatment was received within the first 12.5 hours after symptom onset and increased by an additional 5% from 12.5 to 20 hours. Time to treatment was not associated with any complications., Conclusions and Relevance: This cohort study found evidence that more favorable outcomes (discharge home and survival at 12 months) were achieved when surgical treatment occurred at approximately 12.5 hours. These findings provide more clarity around optimal timelines of treatment with people with aneurysmal SAH; however, additional studies are needed to confirm the findings.

Objective: This study aimed to understand the associations between mindfulness, perceived stress, and work engagement in a very large sample of English-speaking adults, from 130 different countries. It also aimed to assess participants' self-reported changes following a 6-week mindfulness massive open online course (MOOC). Methods: Participants in the 6-week MOOC were invited to complete pre-post online surveys. Cross-sectional associations were assessed using univariate linear models, followed by structural equation models to test mediation pathways in baseline data ( N = 16,697). Self-reported changes in mindfulness, stress and engagement following training were assessed using paired t -tests ( n = 2,105). Results: Each standard deviation unit increase in mindfulness was associated with a 0.52 standard deviation unit decrease in perceived stress, and with 0.06 standard deviation unit increment in work engagement. 73% of the influence of mindfulness on engagement was direct. Following the mindfulness MOOC, participants reported higher mindfulness ( d = 1.16), reduced perceived stress ( d = 1.00) and a small improvement in work engagement ( d = 0.29). Conclusions: Mindfulness was associated with lower perceived stress and higher work engagement in both cross-sectional and longitudinal analyses. These findings support mindfulness as a potentially protective and modifiable personal resource. The MOOC format offers a low cost, highly accessible means for extending the reach and potential benefits of mindfulness training to large numbers of people., Competing Interests: CH and RC are the developers and lead facilitators of the course being evaluated. Neither author receives financial remuneration from either of those roles. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bartlett, Buscot, Bindoff, Chambers and Hassed.)

Background: Within-visit SBP variability is associated with age and SBP, but its long-term clinical significance is unknown. We examined the association between child, adult, and life-time within-visit SBP variability with markers of end-organ damage using data from a 31-year longitudinal study., Methods: Within-visit SBP variability was calculated as the standard deviation of three sitting SBP readings among up to 3010 participants aged 6-18 years (childhood) who were re-measured up to seven times to mid-adulthood. Markers of cardiovascular end-organ damage in adulthood were carotid intima--media thickness, brachial flow-mediated dilatation, carotid distensibility, pulse wave velocity, left ventricular mass index, carotid plaque, and coronary artery calcification., Results: The mean (standard deviation) cumulative within-visit SBP variability was 2.7 (1.5) mmHg in childhood, 3.9 (1.9) mmHg in adulthood and 3.7 (1.5) mmHg across the observed life-time. Childhood within-visit SBP variability was not correlated with its subsequent values measured from 3 to 31 years later. With adjustment for age, sex, cumulative SBP, BMI and serum lipids, neither child, adult, or life-time cumulative within-visit SBP variability associated with markers of cardiovascular end-organ damage. However, higher child, adult, and life-time cumulative SBP significantly associated with higher carotid intima--media thickness, higher pulse wave velocity, lower brachial flow-mediated dilatation, lower carotid distensibility in adulthood., Conclusion: Within-visit SBP variability from childhood to adulthood does not provide additional predictive utility over SBP over the same period of the life course., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Low muscular strength is a risk factor for current and future adverse health outcomes. However, whether levels of muscular strength persist, or track, and if there are distinct muscular strength trajectories across the life course is unclear. This study aimed to explore muscular strength trajectories between childhood and mid-adulthood., Design: Prospective longitudinal study., Methods: Childhood Determinants of Adult Health Study participants had their muscular strength (right and left handgrip, shoulder extension and flexion, and leg strength measured by hand-held, shoulder and leg-back dynamometers, and a combined strength score) assessed in childhood, young adulthood and mid-adulthood. The tracking of muscular strength was quantified between childhood and mid-adulthood (n=385) and young- and mid-adulthood (n=822). Muscular strength trajectory patterns were identified for participants who had their muscular strength assessed at least twice across the life course (n=1280)., Results: Levels of muscular strength were persistent between childhood and mid-adulthood and between young- and mid-adulthood, with the highest tracking correlations observed for the combined strength score (childhood to mid-adulthood: r=0.47, p<0.001; young- to mid-adulthood: r=0.72, p<0.001). Three trajectories of combined muscular strength were identified across the life course; participants maintained average, above average, or below average levels of combined muscular strength., Conclusions: Weak children are likely to become weak adults in midlife unless strategies aimed at increasing muscular strength levels are introduced. Whether interventions aimed at increasing muscular strength could be implemented in childhood to help establish favourable muscular strength trajectories across the life course and in turn, better future health, warrant further attention., (Copyright © 2021 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the presence of coronary artery calcification (CAC), a marker of heart disease in adulthood. However, the relative importance of non-HDL-C levels at specific life stages for CAC remains unclear., Objective: To identify the relative association of non-HDL-C measured at distinct life stages (adolescence, young adulthood, mid-adulthood) with the presence of CAC measured in mid-adulthood., Design, Setting, and Participants: The Cardiovascular Risk in Young Finns Study is a population-based prospective cohort study that started in 1980 with follow-up over 28 years. Participants from 3 population centers (Kuopio, Tampere, and Turku in Finland) represent a convenience sample drawn from the 3 oldest cohorts at baseline (aged 12-18 years in 1980). Data were collected from September 1980 to August 2008. Analysis began February 2020., Exposures: Non-HDL-C levels were measured at 3 life stages including adolescence (aged 12-18 years), young adulthood (aged 21-30 years), and mid-adulthood (aged 33-45 years)., Main Outcomes and Measures: In 2008, CAC was determined from computed tomography and dichotomized as 0 (no CAC, Agatston score = 0) and 1 (presence of CAC, Agatston score ≥1) for analysis. Using a bayesian relevant life course exposure model, the relative association was determined between non-HDL-C at each life stage and the presence of CAC in mid-adulthood., Results: Of 589 participants, 327 (56%) were female. In a model adjusted for year of birth, sex, body mass index, systolic blood pressure, blood glucose level, smoking status, lipid-lowering and antihypertensive medication use, and family history of heart disease, cumulative exposure to non-HDL-C across all life stages was associated with CAC (odds ratio [OR], 1.50; 95% credible interval [CrI], 1.14-1.92). At each life stage, non-HDL-C was associated with CAC and exposure to non-HDL-C during adolescence had the strongest association (adolescence: OR, 1.16; 95% CrI, 1.01-1.46; young adulthood: OR, 1.14; 95% CrI, 1.01-1.43; mid-adulthood: OR, 1.12; 95% CrI, 1.01-1.34)., Conclusions and Relevance: These data suggest that elevated non-HDL-C levels at all life stages are associated with coronary atherosclerosis in mid-adulthood. However, adolescent non-HDL-C levels showed the strongest association with the presence of CAC in mid-adulthood, and greater awareness of the importance of elevated non-HDL-C in adolescence is needed.

Context: The influence of dietary pattern trajectories from youth to adulthood on adult glucose metabolism is unknown., Objective: To identify dietary pattern trajectories from youth to adulthood and examine their associations with adult impaired fasting glucose (IFG)., Methods: Thirty-one-year population-based cohort study among 1007 youths aged 3-18 years at baseline in Finland. Diet intake was assessed in 1980, 1986, 2001, 2007, and 2011. Group-based trajectory modelling was used to identify dietary pattern (identified by factor analysis) trajectories. Adult IFG was measured by the latest available data from 2001, 2007, and 2011., Results: Among 1007 participants, 202 (20.1%) developed IFG and 27 (2.7%) developed type 2 diabetes in adulthood (mean follow-up of 30.7 years; mean [SD] age 40.5 [5.0] years). Three dietary patterns were identified at baseline and were retained in 1986 and 2001: "Traditional Finnish," "High carbohydrate," and "Vegetables and dairy products." Three different patterns were identified in 2007, which remained similar in 2011: "Traditional Finnish and high carbohydrate," "Red meat," and "Healthy." Trajectories of increased or stably medium "red meat" pattern scores from youth to adulthood were detrimentally associated with IFG (relative risk 1.46, 95% CI 1.12-1.90 for Medium (M)-stable/M-large increase vs low-stable trajectory) after adjusting for confounders. This association was slightly reduced after further adjusting for long-term dietary fiber intake., Conclusion: Trajectories of an increased or stably moderate adherence to a "red meat" dietary pattern from youth to adulthood are associated with higher risk of adult IFG. This association is partly explained by low dietary fiber intake., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Life course exposure to passive smoke may predict health, but there are few validated measures. We tested the reliability and validity of a retrospective life course passive smoking questionnaire., Methods: Participants from the third follow-up of the Childhood Determinants of Adult Health study (2014-2019, ages 36-49 years) retrospectively reported mother/father/other household member smoking when living at home during childhood, including duration (years) and smoking location (never/sometimes/always inside house). The severity of exposure index (SEI; sum of mother/father/other years smoked multiplied by smoking location), cumulative years of exposure (CYE; sum of mother/father/other years), and total household smokers (THS) were derived. The reliability of retrospective passive smoking reports was examined with intraclass correlation coefficients (ICCs) using household smoking reported 34 years earlier in 1985 by participants when aged 7-15 years. Construct validity was examined by correlating retrospective passive smoking with participants' smoking in adulthood and lung function in childhood and adulthood., Results: Among 2082 participants (mean±standard deviation [SD], 45.0±2.5 years; 55.2% females), THS ranged from 0 to 5 (mean± SD, 0.9±1.0), CYE ranged from 0 to 106 (mean±SD, 10.5±13.9), and SEI ranged from 0 to 318 (mean±SD, 24.4±36.0). Retrospective measures showed moderate agreement with total household smokers reported in childhood (ICC, 0.58 to 0.62). The retrospective measures were weakly but significantly (p&lt;0.05) correlated with participants' smoking (r=0.13 to 0.15) and lung function (r= -0.05 to -0.06)., Conclusions: The retrospective passive smoking questionnaire showed reasonable reliability and validity. This measure may be useful for epidemiological studies.

Background: Although low child and adult grip strength is associated with adverse cardiometabolic health, how grip strength across the life course associates with type 2 diabetes is unknown. This study identified the relative contribution of grip strength measured at specific life stages (childhood, young adulthood, mid-adulthood) with prediabetes or type 2 diabetes in mid-adulthood., Methods: Between 1985 and 2019, 263 participants had their grip strength measured using an isometric dynamometer in childhood (9-15 years), young adulthood (28-36 years) and mid-adulthood (38-49 years). In mid-adulthood, a fasting blood sample was collected and tested for glucose and glycated haemoglobin (HbA1c). Participants were categorized as having prediabetes or type 2 diabetes if fasting glucose levels were ≥ 5.6 mmol or if HbA1c levels were ≥ 5.7% (≥ 39 mmol/mol). A Bayesian relevant life course exposure model examined the association between lifelong grip strength and prediabetes or type 2 diabetes., Results: Grip strength at each time point was equally associated with prediabetes or type 2 diabetes in mid-adulthood (childhood: 37%, young adulthood: 36%, mid-adulthood: 28%). A one standard deviation increase in cumulative grip strength was associated with 34% reduced odds of prediabetes or type 2 diabetes in mid-adulthood (OR 0.66, 95% credible interval 0.40, 0.98)., Conclusions: Greater grip strength across the life course could protect against the development of prediabetes and type 2 diabetes. Strategies aimed at increasing muscular strength in childhood and maintaining behaviours to improve strength into adulthood could improve future cardiometabolic health. The Association Between Grip Strength Measured in Childhood, Young- and Mid-adulthood and Prediabetes or Type 2 Diabetes in Mid-adulthood.

Background: The role of genetic risk scores associated with adult body mass index (BMI) on BMI levels across the life course is unclear. We examined if a 97 single nucleotide polymorphism weighted genetic risk score (wGRS97) associated with age-related progression in BMI at different life stages and distinct developmental trajectories of BMI across the early life course., Methods: 2188 Cardiovascular Risk in Young Finns Study participants born pre-1980 who had genotype data and objective measurements of height and weight collected up to 8 times from age 6 to 49 years. Associations were examined using Individual Growth Curve analysis, Latent Class Growth Mixture Modelling, and Poisson modified regression., Results: The wGRS97 associated with BMI from age 6 years with peak effect sizes observed at age 30 years (females: 1.14 kg/m 2 ; males: 1.09 kg/m 2 higher BMI per standard deviation increase in wGRS97). The association between wGRS97 and BMI became stronger with age in childhood but slowed in adolescence, especially in females, and weakened at age 35-40 years. A higher wGRS97 associated with an increased BMI velocity in childhood and adulthood, but not with BMI change in adulthood. Compared with belonging to a 'normal stable' life-course trajectory group (normal BMI from childhood to adulthood), a one standard deviation higher wGRS97 associated with a 13-127% increased risk of belonging to a less favourable life-course BMI trajectory group., Conclusions: Individuals with genetic susceptibility to higher adult BMI have higher levels and accelerated rates of increase in BMI in childhood/adolescence, and are at increased risk of having a less favourable life-course BMI trajectory.

Background Whether long-term exposure to overweight or obesity from early life to adulthood has a detrimental influence on health outcomes is unknown. We aimed to investigate whether duration of overweight or obesity from youth to adulthood is associated with adult cardiometabolic risk. Methods and Results A population-based cohort study was performed of 1268 youths, aged 3 to 18 years, with follow-ups at 3, 6, 9, 12, 21, 27, and 31 years. Duration of overweight or obesity over 31-year follow-up was calculated. Adulthood outcomes included type 2 diabetes mellitus, impaired fasting glucose, high insulin levels, high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity, carotid artery compliance, Young elastic modulus, and stiffness index. Rates of overweight/obesity were 7.9% at baseline and 55.9% after 31 years. After adjustment for confounders, longer duration of overweight or obesity was associated with increased risk of all outcomes (relative risk ranged from 1.45-9.06 for type 2 diabetes mellitus, impaired fasting glucose, carotid intima-media thickness, hypertension, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; β from 0.370-0.543 m/s for pulse wave velocity; -0.193 to -0.237 %/10 mm Hg for carotid artery compliance; 52.1-136.8 mm Hg·mm for Young elastic modulus; and 0.554-0.882 for stiffness index). When body mass index was further adjusted, these associations disappeared or were substantially reduced. Detrimental associations of adult body mass index with all outcomes were robust to adjustment for confounders and duration of overweight or obesity. Conclusions Overweight or obesity in adulthood rather than childhood appears to be more important for adult cardiometabolic health.

Objectives: To estimate and compare tri-ponderal mass index (TMI) and body mass index (BMI) at each age from childhood to young adulthood in the prediction of adulthood obesity-related outcomes., Study Design: Participants of this observational study (n = 432) were from a 20-year infancy-onset randomized atherosclerosis prevention trial. BMI and TMI were calculated using weight and height measured annually from participants between ages 2 and 20 years. Outcomes were aortic intima-media thickness (at the age of 15, 17, or 19 years), impaired fasting glucose and elevated insulin levels, homeostasis model assessment of insulin resistance index, serum lipids, and hypertension at the age of 20 years. Poisson regressions, Pearson correlation, logistic regression, and area under the curve (AUC) were used to estimate and/or compare associations and predictive utilities between BMI and TMI with all outcomes., Results: The associations and predictive utilities of BMI and TMI with all outcomes were stronger at older ages. BMI had significantly stronger correlations than TMI with insulin (at age 16 years), systolic blood pressure (age 5-20 years), and triglycerides (age 18 years). BMI had significantly greater predictive utilities than TMI for insulin resistance (at age 14-16 years; difference in AUC = 0.018-0.024), elevated insulin levels (age 14-16 years; difference in AUC = 0.018 and 0.025), and hypertension (age 16 to 20 years; difference in AUC = 0.017-0.022) but they were similar for other outcomes., Conclusions: TMI is not superior to BMI at any ages from childhood to young adulthood in the prediction of obesity-related outcomes in young adulthood., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: To the best of our knowledge, no previous studies have examined the role of youth calcium intake in the development of impaired glucose metabolism, especially those with long-term high calcium intake., Objectives: To examine whether youth and long-term (between youth and adulthood) dietary calcium intake is associated with adult impaired glucose metabolism and type 2 diabetes (T2D)., Design, Setting, and Participants: The Cardiovascular Risk in Young Finns Study is a 31-year prospective cohort study (n = 1134; age, 3 to 18 years at baseline)., Exposures: Dietary calcium intake was assessed at baseline (1980) and adult follow-up visits (2001, 2007, and 2011). Long-term (mean between youth and adulthood) dietary calcium intake was calculated., Main Outcome Measures: Adult impaired fasting glucose (IFG) and T2D., Results: We found no evidence for nonlinear associations between calcium intake and IFG or T2D among females and males (all P for nonlinearity > 0.05). Higher youth and long-term dietary calcium intake was not associated with the risk of IFG or T2D among females or males after adjustment for confounders, including youth and adult body mass index., Conclusions: Youth or long-term dietary calcium intake is not associated with adult risk of developing impaired glucose metabolism or T2D., (Copyright © 2019 Endocrine Society.)

Aims: The relationship between life-course body mass index (BMI) trajectories and adult risk for cardiovascular disease (CVD) is poorly described. In a longitudinal cohort, we describe BMI trajectories from early childhood to adulthood and investigate their association with CVD risk factors [Type 2 diabetes mellitus (T2DM), high-risk lipid levels, hypertension, and high carotid intima-media thickness (cIMT)] in adulthood (34-49 years)., Methods and Results: Six discrete long-term BMI trajectories were identified using latent class growth mixture modelling among 2631 Cardiovascular Risk in Young Finns Study participants (6-49 years): stable normal (55.2%), resolving (1.6%), progressively overweight (33.4%), progressively obese (4.2%), rapidly overweight/obese (4.3%), and persistent increasing overweight/obese (1.2%). Trajectories of worsening or persisting obesity were generally associated with increased risk of CVD outcomes in adulthood (24-49 years) [all risk ratios (RRs) >15, P < 0.05 compared with the stable normal group]. Although residual risk for adult T2DM could not be confirmed [RR = 2.6, 95% confidence interval (CI) = 0.14-8.23], participants who resolved their elevated child BMI had similar risk for dyslipidaemia and hypertension as those never obese or overweight (all RRs close to 1). However, they had significantly higher risk for increased cIMT (RR = 3.37, 95% CI = 1.80-6.39)., Conclusion: The long-term BMI trajectories that reach or persist at high levels associate with CVD risk factors in adulthood. Stabilizing BMI in obese adults and resolving elevated child BMI by adulthood might limit and reduce adverse cardiometabolic profiles. However, efforts to prevent child obesity might be most effective to reduce the risk for adult atherosclerosis.

Background and Objectives: Youth with high BMI who become nonobese adults have the same cardiovascular risk factor burden as those who were never obese. However, the early-life BMI trajectories for overweight or obese youth who avoid becoming obese adults have not been described. We aimed to determine and compare the young-childhood BMI trajectories of participants according to their BMI status in youth and adulthood., Methods: Bayesian hierarchical piecewise regression modeling was used to analyze the BMI trajectories of 2717 young adults who had up to 8 measures of BMI from childhood (ages 3-18 years) to adulthood (ages 34-49 years)., Results: Compared with those with persistently high BMI, those who resolved their high youth BMI by adulthood had lower average BMI at age 6 years and slower rates of BMI change from young childhood. In addition, their BMI levels started to plateau at 16 years old for females and 21 years old for males, whereas the BMI of those whose high BMI persisted did not stabilize until 25 years old for male subjects and 27 years for female subjects. Compared with those youth who were not overweight or obese and who remained nonobese in adulthood, those who developed obesity had a higher BMI rate of change from 6 years old, and their BMI continued to increase linearly until age 30 years., Conclusions: Efforts to alter BMI trajectories for adult obesity should ideally commence before age 6 years. The natural resolution of high BMI starts in adolescence for males and early adulthood for females, suggesting a critical window for secondary prevention., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background: Bayesian hierarchical piecewise regression (BHPR) modeling has not been previously formulated to detect and characterise the mechanism of trajectory divergence between groups of participants that have longitudinal responses with distinct developmental phases. These models are useful when participants in a prospective cohort study are grouped according to a distal dichotomous health outcome. Indeed, a refined understanding of how deleterious risk factor profiles develop across the life-course may help inform early-life interventions. Previous techniques to determine between-group differences in risk factors at each age may result in biased estimate of the age at divergence., Methods: We demonstrate the use of Bayesian hierarchical piecewise regression (BHPR) to generate a point estimate and credible interval for the age at which trajectories diverge between groups for continuous outcome measures that exhibit non-linear within-person response profiles over time. We illustrate our approach by modeling the divergence in childhood-to-adulthood body mass index (BMI) trajectories between two groups of adults with/without type 2 diabetes mellitus (T2DM) in the Cardiovascular Risk in Young Finns Study (YFS)., Results: Using the proposed BHPR approach, we estimated the BMI profiles of participants with T2DM diverged from healthy participants at age 16 years for males (95% credible interval (CI):13.5-18 years) and 21 years for females (95% CI: 19.5-23 years). These data suggest that a critical window for weight management intervention in preventing T2DM might exist before the age when BMI growth rate is naturally expected to decrease. Simulation showed that when using pairwise comparison of least-square means from categorical mixed models, smaller sample sizes tended to conclude a later age of divergence. In contrast, the point estimate of the divergence time is not biased by sample size when using the proposed BHPR method., Conclusions: BHPR is a powerful analytic tool to model long-term non-linear longitudinal outcomes, enabling the identification of the age at which risk factor trajectories diverge between groups of participants. The method is suitable for the analysis of unbalanced longitudinal data, with only a limited number of repeated measures per participants and where the time-related outcome is typically marked by transitional changes or by distinct phases of change over time.

Background: Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures., Methods and Results: Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3-18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; P =0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; P <0.01). The overall net reclassification improvement and integrated discrimination improvement were significant for all outcomes., Conclusions: The inclusion of weighted genetic risk scores to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood., (© 2017 American Heart Association, Inc.)

Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are modifiable risk factors for cardiovascular disease. Several genetic loci for predisposition to abnormal LDL-C, HDL-C and TG have been identified. However, it remains unclear whether these loci are consistently associated with serum lipid levels at each age or with unique developmental trajectories. Therefore, we assessed the association between genome wide association studies (GWAS) derived polygenic genetic risk scores and LDL-C, HDL-C, and triglyceride trajectories from childhood to adulthood using data available from the 27-year European 'Cardiovascular Risk in Young Finns' Study. For 2,442 participants, three weighted genetic risk scores (wGRSs) for HDL-C (38 SNPs), LDL-C (14 SNPs) and triglycerides (24 SNPs) were computed and tested for association with serum lipoprotein levels measured up to 8 times between 1980 and 2011. The categorical analyses revealed no clear divergence of blood lipid trajectories over time between wGRSs categories, with participants in the lower wGRS quartiles tending to have average lipoprotein concentrations 30 to 45% lower than those in the upper-quartile wGRS beginning at age 3 years and continuing through to age 49 years (where the upper-quartile wGRS have 4-7 more risk alleles than the lower wGRS group). Continuous analyses, however, revealed a significant but moderate time-dependent genetic interaction for HDL-C levels, with the association between HDL-C and the continuous HDL-C risk score weakening slightly with age. Conversely, in males, the association between the continuous TG genetic risk score and triglycerides levels tended to be lower in childhood and become more pronounced after the age of 25 years. Although the influence of genetic factors on age-specific lipoprotein values and developmental trajectories is complex, our data show that wGRSs are highly predictive of HDL-C, LDL-C, and triglyceride levels at all ages.

Generally, sigmoid curves are used to describe the growth of animals over their lifetime. However, because growth rates often differ over an animal's lifetime a single curve may not accurately capture the growth. Broken-stick models constrained to pass through a common point have been proposed to describe the different growth phases, but these are often unsatisfactory because essentially there are still two functions that describe the lifetime growth. To provide a single, converged model to age animals with disparate growth phases we developed a smoothly joining two-phase nonlinear function (SJ2P), tailored to provide a more accurate description of lifetime growth of the macropod, the Tasmanian pademelon Thylogale billardierii. The model consists of the Verhulst logistic function, which describes pouch-phase growth--joining smoothly to the Brody function, which describes post-pouch growth. Results from the model demonstrate that male pademelons grew faster and bigger than females. Our approach provides a practical means of ageing wild pademelons for life history studies but given the high variability of the data used to parametrise the second growth phase of the model, the accuracy of ageing of post-weaned animals is low: accuracy might be improved with collection of longitudinal growth data. This study provides a unique, first robust method that can be used to characterise growth over the lifespan of pademelons. The development of this method is relevant to collecting age-specific vital rates from commonly used wildlife management practices to provide crucial insights into the demographic behaviour of animal populations.

The distribution and aminopeptidase activity of prokaryotes were investigated along a natural continuous salinity gradient in a hypersaline coastal lagoon, the Coorong, South Australia. The abundance of prokaryotes significantly increased from brackish to hypersaline waters and different sub-populations, defined by flow cytometry, were observed along the salinity gradient. While four sub-populations were found at each station, three additional ones were observed for 8.3% and 13.4%, suggesting a potential modification in the composition of the prokaryotic communities and/or a variation of their activity level along the salinity gradient. The aminopeptidase activity highly increased along the gradient and salinity appeared as the main factor favouring this enzymatic activity. However, while the aminopeptidase activity was dominated by free enzymes for salinities ranging from 2.6% to 13.4%, cell-attached aminopeptidase activity was predominant in more saline waters (i.e. 15.4%). Changes in substrate structure and availability, strongly related to salinity, might (i) modify patterns of both aminopeptidase activities (free and cell-associated enzymes) and (ii) obligate the prokaryotic communities to modulate rapidly their aminopeptidase activity according to the nutritive conditions available along the gradient.

Background: Picophytoplankton (i.e. cyanobacteria and pico-eukaryotes) are abundant and ecologically critical components of the autotrophic communities in the pelagic realm. These micro-organisms colonized a variety of extreme environments including high salinity waters. However, the distribution of these organisms along strong salinity gradient has barely been investigated. The abundance and community structure of cyanobacteria and pico-eukaryotes were investigated along a natural continuous salinity gradient (1.8% to 15.5%) using flow cytometry., Results: Highest picophytoplankton abundances were recorded under salinity conditions ranging between 8.0% and 11.0% (1.3 x 106 to 1.4 x 106 cells ml-1). Two populations of picocyanobacteria (likely Synechococcus and Prochlorococcus) and 5 distinct populations of pico-eukaryotes were identified along the salinity gradient. The picophytoplankton cytometric-richness decreased with salinity and the most cytometrically diversified community (4 to 7 populations) was observed in the brackish-marine part of the lagoon (i.e. salinity below 3.5%). One population of pico-eukaryote dominated the community throughout the salinity gradient and was responsible for the bloom observed between 8.0% and 11.0%. Finally only this halotolerant population and Prochlorococcus-like picocyanobacteria were identified in hypersaline waters (i.e. above 14.0%). Salinity was identified as the main factor structuring the distribution of picophytoplankton along the lagoon. However, nutritive conditions, viral lysis and microzooplankton grazing are also suggested as potentially important players in controlling the abundance and diversity of picophytoplankton along the lagoon., Conclusions: The complex patterns described here represent the first observation of picophytoplankton dynamics along a continuous gradient where salinity increases from 1.8% to 15.5%. This result provides new insight into the distribution of pico-autotrophic organisms along strong salinity gradients and allows for a better understanding of the overall pelagic functioning in saline systems which is critical for the management of these precious and climatically-stress ecosystems.