Life course predictors of child emotional distress during the COVID-19 pandemic: Findings from a prospective intergenerational cohort study.

BACKGROUND: We examine precursors of child emotional distress during the COVID-19 pandemic in a prospective intergenerational Australian cohort study. METHODS: Parents (N = 549, 60% mothers) of 934 1-9-year-old children completed a COVID-19 specific module in 2020 and/or 2021. Decades prior, a broad range of individual, relational and contextual factors were assessed during parents' own childhood, adolescence and young adulthood (7-8 to 27-28 years old; 1990-2010) and again when their children were 1 year old (2012-2019). RESULTS: After controlling for pre-pandemic socio-emotional behaviour problems, COVID-19 child emotional distress was associated with a range of pre-pandemic parental life course factors including internalising difficulties, lower conscientiousness, social skills problems, poorer relational health and lower trust and tolerance. Additionally, in the postpartum period, pre-pandemic parental internalising difficulties, lower parental warmth, lower cooperation and fewer behavioural competencies predicted child COVID-19 emotional distress. CONCLUSIONS: Findings highlight the importance of taking a larger, intergenerational perspective to better equip young populations for future adversities. This involves not only investing in child, adolescent, and young adult emotional and relational health, but also in parents raising young families.

Circadian variation in muscle force output in males using isokinetic, isometric dynamometry: can we observe this in multi-joint movements using the muscleLab force-velocity encoder and are they similar in peak and magnitude?

We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (Trec, Tm) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s-1 for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, Trec and Tm were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for Trec and Tm at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C, p < 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h (p < 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.

Effects of Supplementing Zinc Magnesium Aspartate on Sleep Quality and Submaximal Weightlifting Performance, following Two Consecutive Nights of Partial Sleep Deprivation.

Purpose: We examined whether supplementation of zinc magnesium aspartate (ZMA), while partially sleep deprived, was beneficial to sleep quality and subsequent morning (07:00 h) submaximal weightlifting. Methods: Using a double-blinded, randomized counterbalanced design, sixteen trained males were recruited and completed six sessions: (i) one repetition max (1 RM) for bench press and back squat; (ii) two familiarisation sessions; (iii) three conditions with 4 h sleep and either: ZMA, placebo (PLA), or NoPill control (NoPill). Submaximal exercise session consisted of three repetitions at 40, 60 and 80% of 1 RM for bench press and back squat. Average power (AP), average velocity (AV), peak velocity (PV), displacement (D) and time-to-peak velocity (tPV) were recorded using MuscleLab linear encoders. Data were analysed using a general linear model with repeated measures and linear correlation. Results: No significant main effect for condition was found for performance values or subjective ratings of fatigue. Main effect for "load" on the bar was found, where AP and tPV values increased with load (p < 0.05). No significant relationship between dose of zinc or magnesium ingested and change in performance for 80% 1 RM power-outputs was found. Conclusion: Supplementation of ZMA for two nights of partial sleep deprivation had no effect on sleep or subsequent morning performance.

The influence of natural disasters and multiple natural disasters on self-harm and suicidal behaviour: findings from a nationally representative cohort study of Australian adolescents.

Few studies have examined the relationship between exposure to natural hazards and suicide and self-harm in youth. We extend prior research by investigating the association between multiple disasters and the risks of self-harm and suicide longitudinally in a nationally representative longitudinal cohort of adolescents 14 to 15 years to 18-19 years of age. Natural disasters were identified through parental self-reports for the local area. Different types of multiple disaster exposures were investigated including compound disasters (two or more disasters occurring in the last 12 months), cascading disasters (a disaster that leads to another disaster in the subsequent wave) and consecutive disasters (multiple disasters within the last two years or over an eight-year period). Using 8,714 person-waves of data from 2,908 adolescents, findings from random effect models suggest that parental reports of fire or floods increase the risk of self-harm ideation, self-harm, and suicidal ideation. Compound disasters of fire/flood and drought were also associated with increased risk of suicidal thoughts. Cascading disasters of drought followed by fire/flood increased the risks of self-harm but recurrent consecutive droughts were associated with lower risks of suicidal ideation. Australian adolescents are exposed to high rates of natural disasters that increase the risk of self-harm and thoughts of self-harm and suicide. Climate change will increase risk of natural disaster exposure for all countries. Despite these increased risks, there was resilience to disaster exposure particularly in the case of recurrent drought suggesting that youth, families and communities may well develop protective strategies to support mental health.

Diurnal variation in variables related to cognitive performance: a systematic review.

PURPOSE: The aim of this review was to assess current evidence regarding changes in cognitive function according to time-of-day (TOD) and assess the key components of research design related to manuscripts of chronobiological nature. METHODS: An English-language literature search revealed 523 articles through primary database searches, and 1868 via organization searches/citation searching. The inclusion criteria were met by eleven articles which were included in the review. The inclusion criteria set were healthy adult males, a minimum of two timepoints including morning and evening, cognitive measures of performance, and peer-reviewed academic paper. RESULTS: It was established that cognitive performance varies with TOD and the degree of difference is highly dependent on the type of cognitive task with differences ranging from 9.0 to 34.2% for reaction time, 7.3% for alertness, and 7.8 to 40.3% for attention. The type of cognitive function was a determining factor as to whether the performance was better in the morning, evening, or afternoon. CONCLUSION: Although some studies did not establish TOD differences, reaction time and levels of accuracy were highest in the evening. This implies that cognitive processes are complex, and existing research is contradictory. Some studies or cognitive variables did not show any measurable TOD effects, which may be due to differences in methodology, subjects involved, testing protocols, and confounding factors. No studies met all requirements related to chronobiological research, highlighting the issues around methodology. Therefore, future research must use a rigorous, approach, minimizing confounding factors that are specific to examinations of TOD.

Is implementing a post-lunch nap beneficial on evening performance, following two nights partial sleep restriction?

We have investigated the effects that partial-sleep-restriction (PSR0, 4-h sleep retiring at 02:30 and waking at 06:30 h for two consecutive nights) have on 07:30 and 17:00 h cognitive and submaximal weightlifting; and whether this performance improves at 17:00 h following a 13:00 h powernap (0, 30 or 60-min). Fifteen resistance-trained males participated in this study. Prior to the experimental protocol, one repetition max (1RM) bench press and back squat, normative habitual sleep and food intake were recorded. Participants were familiarised with the testing protocol, then completed three experimental conditions: (i) PSR with no nap (PSR0); (ii) PSR with a 30-min nap (PSR30) and (iii) PSR with a 60-min nap (PSR60). Conditions were separated by 7 days with trial order counterbalanced. Intra-aural temperature, Profile of Mood Scores, word-colour interference, alertness and tiredness values were measured at 07:30, 11:00, 14:00, 17:00 h on the day of exercise protocol. Following final temperature measurements at 07:30 h and 17:00 h, participants completed a 5-min active warm-up before performing three repetitions of left and right-hand grip strength, followed by three repetitions at each incremental load (40, 60 and 80% of 1RM) for bench press and back squat, with a 5-min recovery between each repetition. A linear encoder was attached perpendicular to the bar used for the exercises. Average power (AP), average velocity (AV), peak velocity (PV), displacement (D) and time-to-peak velocity (tPV) were measured (MuscleLab software) during the concentric phase of the movements. Data were analysed using general linear models with repeated measures. The main findings were that implementing a nap at 13:00 h had no effect on measures of strength (grip, bench press or back squat). There was a main effect for time of day with greatest performance at 17:00 h for measures of strength. In addition to a significant effect for "load" on the bar for bench press and back squat where AP, AV, PV, D values were greatest at 40% (P < 0.05) and decreased with increased load, whereas tPV and RPE values increased with load; despite this no interaction of "load and condition" were present. A post lunch nap of 30- and 60-minute durations improved mood state, with feelings of alertness, vigour and happiness highest at 17:00 h, in contrast to confusion, tiredness and fatigue (P < 0.05), which were greater in the morning (07:30 h). The word-colour interference test, used as an indicator of cognitive function, reported significant main effect for condition, with the highest total test score in PSR60 condition (P = 0.015). In summary, unlike strength measures the implementation of a 30 or 60-minute nap improved cognitive function when in a partially sleep restricted state, compared to no nap.

Effects of treatment dosage of whole-body cryotherapy upon post-match recovery of endocrine and biochemical markers in elite rugby league players: An experimental study.

Background and Aims: The use of whole-body cryotherapy (WBC) for athletic recovery is becoming increasingly popular despite the lack of evidence supporting the dosage parameters in its implementation. The aim of the current study was to investigate the dose-response effects of WBC following match-play in elite rugby league players. Methods: We observed endocrine (salivary cortisol and testosterone) and biochemical (creatine kinase) responses following three separate post-match recovery periods in elite rugby league players. Comparisons were made between a single exposure (3 min at -120°C to --135°C) of WBC to two consecutive exposures (2 × 3 min), to a control (no exposure) during the recovery trials. Recovery characteristics were measured 36 h prematch, immediately postmatch, and 60 h postmatch. Results: Cortisol concentrations remained unchanged in its pattern of response during the postmatch recovery periods across all WBC doses. Testosterone concentrations increased significantly (p < 0.0005) at 60 h, in the WBC2 trial. The Testosterone:Cortisol ratio increased significantly (p < 0.0005) at 60 h in the WBC2 trial, while during the WBC0 trial it did not recover to baseline levels. No significant effect on creatine kinase concentration was observed, although a statistical trend was shown in WBC2 for improved reduction of this marker at 60 h. Conclusions: These findings suggest that two, consecutive exposures to WBC immediately following fatiguing rugby league competition appear to stimulate an increase to the anabolic endocrine profile of participants by 60 h post-match, and may reduce the CK concentration. Coaches and athletes should consider the treatment dosage of WBC when used to optimize the desired response following a high-stress environment.

The effect of exercise interventions on quality of life in patients with multiple myeloma: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: To determine the effect of exercise interventions on quality of life in adults with multiple myeloma. METHODS: A literature search of 10 sources was performed in June 2022 to identify eligible studies for synthesis. INCLUSION CRITERIA: randomised controlled trials comparing the effect of exercise interventions with usual care in adults with a diagnosis of multiple myeloma. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. Meta-analysis was performed using a random-effects model with inverse variance and 95% confidence intervals. Forest plots were constructed to present pooled data. RESULTS: Five RCTs, which included a total of 519 participants, were selected for inclusion. Four of the five studies were included in the meta-analysis. The mean participant age ranged from 55 to 67 years old. All studies included an aerobic exercise component. Intervention length ranged from 6 to 30 weeks. Meta-analysis of 118 participants showed that exercise interventions had no impact on global quality of life (MD = 2.15, 95% CI: - 4.67, 8.97, p = 0.54, I2 = 0%). Exercise interventions negatively impacted participant grip strength (MD: - 3.69, 95% CI: - 7.12, -0.26, p = 0.03, I2 = 0%) according to pooled data from 186 participants. CONCLUSION: Exercise interventions have no positive impact on the quality of life of patients with multiple myeloma. The analysis is limited by a high risk of bias across included studies and low certainty evidence. Further high-quality trials are needed to assess the role of exercise in patients with multiple myeloma.

Socioeconomic disadvantage and polygenic risk for high BMI magnify obesity risk across childhood: a longitudinal, population, cohort study.

BACKGROUND: Across the life course, socioeconomic disadvantage disproportionately afflicts those with genetic predispositions to inflammatory diseases. We describe how socioeconomic disadvantage and polygenic risk for high BMI magnify the risk of obesity across childhood, and using causal analyses, explore the hypothetical impact of intervening on socioeconomic disadvantage to reduce adolescent obesity. METHODS: Data were drawn from a nationally representative Australian birth cohort, with biennial data collection between 2004 and 2018 (research and ethics committee approved). We generated a polygenic risk score for BMI using published genome-wide association studies. We measured early-childhood disadvantage (age 2-3 years) with a neighbourhood census-based measure and a family-level composite of parent income, occupation, and education. We used generalised linear regression (Poisson-log link) to estimate the risk of overweight or obesity (BMI ≥85th percentile) at age 14-15 years for children with early-childhood disadvantage (quintiles 4-5) versus average (quintile 3) and least disadvantage (quintiles 1-2), for those with high and low polygenic risk separately. FINDINGS: For 1607 children (n=796 female, n=811 male; 31% of the original cohort [N=5107]), polygenic risk and disadvantage were both associated with overweight or obesity; effects of disadvantage were more marked as polygenic risk increased. Of children with polygenic risk higher than the median (n=805), 37% of children living in disadvantage at age 2-3 years had an overweight or obese BMI by adolescence, compared with 26% of those with least disadvantage. For genetically vulnerable children, causal analyses indicated that early neighbourhood intervention to lessen disadvantage (to quintile 1-2) would reduce risk of adolescent overweight or obesity by 23% (risk ratio 0·77; 95% CI 0·57-1·04); estimates for improving family environments were similar (0·59; 0·43-0·80). INTERPRETATION: Actions addressing socioeconomic disadvantage could mitigate polygenic risk for developing obesity. This study benefits from population-representative longitudinal data but is limited by sample size. FUNDING: Australian National Health and Medical Research Council.

Factor structure of the Mini-Maternal Behavior Q-Sort and associations with infant attachment: Informing precision in research and intervention.

We examined the factor structure of parental sensitivity to infants as assessed by the Mini-Maternal Behavior Q-Sort (Mini-MBQS), a 25-item short-form of the original 90-item MBQS. We aimed to: (1) identify latent factors of the Mini-MBQS; and (2) validate each factor by testing associations with infant attachment classifications. Data on parent-infant dyads (n = 313; 222 mothers with 281 children, 29 fathers with 32 children) were drawn from a three-generation Australian cohort study. Exploratory Factor Analysis and Exploratory Structural Equation Modelling examined the structure of the Mini-MBQS. Two latent Mini-MBQS factors were identified, requiring 8 of 25 original items: (1) Attention and Responsiveness and (2) Contingency in Interactions. Infants with insecure attachment classifications had parents with lower sensitivity across both factors relative to infants classified secure. In particular, infants with resistant attachment classifications had parents with notably low Contingency in Interactions scores. Infants with disorganised attachment classifications had parents with the lowest relative sensitivity across both factors, and in these dyads Attention and Responsiveness scores were especially low. Results provide an empirically derived factor structure for the Mini-MBQS. Two subscales, each with significant infant attachment associations, may improve precision in clinical intervention and research translation.

Age at arrival and integration outcomes of refugee youth and emerging adults: a longitudinal study.

Age at arrival is one factor that could influence the integration of humanitarian migrants, especially for children and teenagers. Previous research has focused on the influence of the age at arrival on education, employment, social and language learning outcomes, but there is limited research, especially for longitudinal study, on other important measures of integration. Moreover, young adult and adolescent refugees, and the relationship between age and integration outcomes are under-studied. To address these gaps, this study examined the relationships between age at arrival and different dimensions of integration of young refugees in Australia, using five years' panel data from the Building a New Life in Australia (BNLA) longitudinal study from 2013 to 2018 (282 individuals). Our findings indicate that age at arrival is significantly correlated with multiple integration outcomes. Old entrants tend to have a higher probability of having a paid job but have poorer mental health and English proficiency. On the other hand, older entrants were more likely to know their rights well compared to younger entrants at arrival. However, younger entrants' knowledge of their rights overtook older entrants four to five years after their arrival. These findings suggest that a shorter assessment process and enabling earlier entry especially among refugee youth and young adults could effectively improve their future settlement outcomes under the current humanitarian policies and system.

Children's Relative Age and Medicine Treatment for Attention-Deficit/Hyperactivity Disorder Across Australian Jurisdictions with Different School Enrolment Policies.

Background: Children who are relatively young for their school grade are more likely to receive treatment for attention-deficit/hyperactivity disorder (ADHD). It is unclear whether the phenomenon also exists across Australia or is impacted by the school enrolment policy in place. Objective: We evaluated the association between children's relative age and initiation of ADHD medicines across Australian jurisdictions with different school enrolment policies and rates of delayed school entry. Methods: We used Australia-wide dispensing data for a 15% random sample of children 4-9 years of age in 2013-2017 to create a nationwide cohort. Due to high rates of delayed school entry in New South Wales (NSW), we used linked prescribing and education data for a cohort of NSW residents starting school in 2009 and 2012. We estimated incidence rate ratios (IRRs) for ADHD medicine across children's birth month, sex, and jurisdiction. We used asthma medicines as a negative control. Results: For girls, we observed a relative age effect in three out of five jurisdictions, with an IRR ranging from 1.3 to 2.8, comparing the youngest versus oldest birth month thirds. We observed more modest effects among boys, ranging from null to 1.5-fold. In NSW, the relatively youngest boys were less likely to initiate stimulant medicines than the oldest (IRR = 0.5, 95% confidence interval 0.29-0.78). We did not observe a relative age effect for initiation of asthma medicines. Conclusions: In jurisdictions with low rates of delayed entry, relatively young children were more likely to initiate ADHD medicines than their older classmates. We observed the inverse association in NSW where delayed entry was highest, likely reflecting the characteristics and needs of children who delay school entry for 1 year and become the oldest children in the grade. Increased awareness around children's maturity differences and school readiness may enhance appropriate diagnosis and treatment of ADHD.

Daily variation in time-trial sporting performance: A systematic review.

Few functional measures related to time-trial display diurnal variation. The diversity of tests/protocols used to assess time-trial performance on diurnal effects and the lack of a standardised approach hinder agreement in the literature. Therefore, the aims of the present study were to investigate and systematically review the evidence relating to time-of-day differences in time-trial measures and to examine the main aspects related to research design important for studies of a chronobiological nature. The entire content of Manipal Academy of Higher Education electronic library and Qatar National Library, and electronic databases: PubMed (MEDLINE), Scopus and Web of Science were searched. Research studies published in peer-reviewed journals and non-peer reviewed studies, conducted in male adult participants aged ≥18 y before November 2021 were screened/included. Studies assessing tests related to time-trials in any modality between a minimum of 2 time-points during the day (morning [06:30-10:30 h] vs evening [14:30-20:00 h]) were deemed eligible. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence to inform recommendations. The primary search revealed that a total of 10 from 40 articles were considered eligible and subsequently included. Six were conducted using cycling, two using running and two using swimming as the mode of exercise. Distances ranged from 1 to 16.1-km in distance or 15 to 20-min time in the cycling and running time-trials, and 50 to 200-m in the swimming time-trials. Only four studies found one or several of their performance variables to display daily variations, with significantly better values in the evening; while six studies found no time-of-day significance in any variables assessed. The magnitude of difference ranged from 2.9% to 7.1% for performance time to complete a cycling time-trial, while running and swimming did not find any differences for performance time. Power output during a 16.1-km time trial in cycling also found evening performance to be significantly better by 10%. The only other observed differences were stroke rate and stroke length during a swimming time-trial and stroke rate (cycles.min-1) during a cycling time-trial. The magnitude of difference is dependent on exercise modality, individual chronotype, the training status of the individual and sample size differences. The lack of diurnal variation present in the majority of studies can in-part be explained with some of the methodological limitations and issues present related to quality and control. It is paramount that research assessing diurnal variation in performance uses appropriate session timings around the core body temperature minimum (~05:00 h; morning) and maximum (~17:00 h; evening). Although, differences in motivation/arousal, habitual training times, chronotypes and genotypes could provide an explanation as to why some studies/variables did not display time-of-day variation, more work is needed to provide an accurate conclusion. There is a clear demand for a rigorous, standardised approach to be adopted by future investigations which control factors that specifically relate to investigations of time-of-day, such as appropriate familiarisation, counterbalancing the order of administration of tests, providing sufficient recovery time between sessions and testing within a controlled environment.

Impact of displacement context on psychological distress in refugees resettled in Australia: a longitudinal population-based study.

AIMS: Refugees typically spend years in a state of protracted displacement prior to permanent resettlement. Little is known about how various prior displacement contexts influence long-term mental health in resettled refugees. In this study, we aimed to determine whether having lived in refugee camps v. community settings prior to resettlement impacted the course of refugees' psychological distress over the 4 years following arrival in Australia. METHODS: Participants were 1887 refugees who had taken part in the Building a New Life in Australia study, which comprised of five annual face-to-face or telephone surveys from the year of first arrival in Australia. RESULTS: Latent growth curve modelling revealed that refugees who had lived in camps showed greater initial psychological distress (as indexed by the K6) and faster decreases in psychological distress in the 4 years after resettling in Australia, compared to those who had lived in community settings. Investigation of refugee camp characteristics revealed that poorer access to services in camps was associated with greater initial distress after resettlement, and greater ability to meet one's basic needs in camps was associated with faster decreases in psychological distress over time. CONCLUSIONS: These findings highlight the importance of the displacement context in influencing the course of post-resettlement mental health. Increasing available services and meeting basic needs in the displacement environment may promote better mental health outcomes in resettled refugees.

Inequalities in the distribution of COVID-19-related financial difficulties for Australian families with young children.

BACKGROUND: We examine (1) the frequency of financial difficulties in Australian families with young children (0-8 years) in the early and later phases of the pandemic; (2) the extent to which parents' pre-pandemic socio-economic disadvantage (SED) predicted financial difficulties; and (3) whether grandparent intergenerational SED further amplified this risk. METHOD: Data: Australian Temperament Project (ATP; established 1983, N = 2443) and ATP Generation 3 study (ATPG3; established 2012; N = 702), of which 74% (N = 553) completed a COVID-specific module in the early (May-September 2020) and/or later (October-December 2021) phases of the pandemic. OUTCOMES: Parent-reported loss of employment/reduced income, difficulty paying for essentials, and financial strain. EXPOSURES: Pre-pandemic parent and grandparent education and occupation. ANALYSIS: Logistic regressions, estimated via generalized estimating equations, were used to examine associations between the pre-pandemic SED of parents and grandparents and their interaction with financial difficulties, adjusting for potential confounders. RESULTS: At both pandemic time points, a third of parents reported adverse financial impacts (early: 34%, 95% confidence interval [CI] = 30-38; later: 32%, 95% CI = 28-36). Each standard deviation increase in the parents' pre-pandemic SED was associated with a 36% increase in the odds of reporting multiple financial difficulties (odds ratio [OR] = 1.36, 95% CI = 1.04-1.78). There was little evidence of an interaction between the SED of parents and grandparents. CONCLUSIONS: Financial impacts related to the COVID-19 pandemic were common and, irrespective of grandparent SED, disproportionately borne by parents with higher pre-pandemic SED. Given the well-established relationship between disadvantage and child health and development, sustained and well-targeted government supports will be critical to minimizing adverse impacts in years to come.

Control of backbone chemistry and chirality boost oligonucleotide splice switching activity.

Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment of neuromuscular disease such as Duchenne muscular dystrophy has been an advance for the splice-switching field, current SSO chemistries have shown limited clinical benefit due to poor pharmacology. To overcome limitations of existing technologies, we engineered chimeric stereopure oligonucleotides with phosphorothioate (PS) and phosphoryl guanidine-containing (PN) backbones. We demonstrate that these chimeric stereopure oligonucleotides have markedly improved pharmacology and efficacy compared with PS-modified oligonucleotides, preventing premature death and improving median survival from 49 days to at least 280 days in a dystrophic mouse model with an aggressive phenotype. These data demonstrate that chemical optimization alone can profoundly impact oligonucleotide pharmacology and highlight the potential for continued innovation around the oligonucleotide backbone. More specifically, we conclude that chimeric stereopure oligonucleotides are a promising splice-switching modality with potential for the treatment of neuromuscular and other genetic diseases impacting difficult to reach tissues such as the skeletal muscle and heart.

Daily variation in performance measures related to anaerobic power and capacity: A systematic review.

Numerous functional measures related to anaerobic performance display daily variation. The diversity of tests and protocols used to assess anaerobic performance related to diurnal effects and the lack of a standardized approach have hindered agreement in the literature. Therefore, the aim of the present study was to investigate and systematically review the evidence relating to time-of-day differences in anaerobic performance measures. The entire content of PubMed (MEDLINE), Scopus, SPORTDiscus® (via EBSCOhost) and Web of Science and multiple electronic libraries were searched. Only experimental research studies conducted in male adult participants aged ≥ 18 yrs before May 2021 were included. Studies assessing tests related to anaerobic capacity or anaerobic power between a minimum of two time-points during the day (morning vs evening) were deemed eligible. The primary search revealed that a total of 55 out of 145 articles were considered eligible and subsequently included. Thirty-nine studies assessed anaerobic power and twenty-five anaerobic capacity using different modes of exercise and test protocols. Forty-eight studies found several of their performance variables to display time-of-day effects, with higher values in the evening than the morning, while seven studies did not find any time-of-day significance in any variables which were assessed. The magnitude of difference is dependent on the modality and the exercise protocol used. Performance measures for anaerobic power found jump tests displayed 2.7 to 12.3% differences, force velocity tests ~8% differences, sprint tests 2.7 to 11.3% differences and 5-m multiple shuttle run tests 3.7 to 13.1% differences in favour of the evening. Performance measures for anaerobic capacity found Wingate test to display 1.8 to 11.7% differences and repeated sprint tests to display 3.4 to 10.2% differences. The only test not to display time-of-day differences was the running based anaerobic sprint test (RAST). Time-of-day variations in anaerobic performance has previously been partially explained by higher core-body and/or muscle temperature and better muscle contractile properties in the afternoon, although recent findings suggest that differences in methodology, motivation/arousal, habitual training times and chronotypes could provide additional explanations. There is a clear demand for a rigorous, standardised approach to be adopted by future investigations which control factors that specifically relate to investigations of time-of-day.

Goldilocks Days: optimising children's time use for health and well-being.

BACKGROUND: One size rarely fits all in population health. Differing outcomes may compete for best allocations of time. Among children aged 11-12 years, we aimed to (1) describe optimal 24-hour time use for diverse physical, cognitive/academic and well-being outcomes, (2) pinpoint the 'Goldilocks Day' that optimises all outcomes and (3) develop a tool to customise time-use recommendations. METHODS: In 2004, the Longitudinal Study of Australian Children recruited a nationally-representative cohort of 5107 infants with biennial follow-up waves. We used data from the cross-sectional Child Health CheckPoint module (2015-2016, n=1874, 11-12 years, 51% males). Time use was from 7-day 24-hour accelerometry. Outcomes included life satisfaction, psychosocial health, depressive symptoms, emotional problems, non-verbal IQ; vocabulary, academic performance, adiposity, fitness, blood pressure, inflammatory biomarkers, bone strength. Relationships between time use and outcomes were modelled using compositional regression. RESULTS: Optimal daily durations varied widely for different health outcomes (sleep: 8.3-11.4 hours; sedentary: 7.3-12.2 hours; light physical activity: 1.7-5.1 hours; moderate-to-vigorous physical activity (MVPA): 0.3-2.7 hours, all models p≤0.04). In general, days with highest physical activity (predominantly MVPA) and low sedentary time were optimal for physical health, while days with highest sleep and lowest sedentary time were optimal for mental health. Days with highest sedentary time and lowest physical activity were optimal for cognitive health. The overall Goldilocks Day had 10 hours 21 min sleep, 9 hours 44 min sedentary time, 2 hours 26 min light physical activity and 1 hour 29 min MVPA. Our interactive interface allows personalisation of Goldilocks Days to an individual's outcome priorities. CONCLUSION: 'Goldilocks Days' necessitate compromises based on hierarchies of priorities for health, social and economic outcomes.