Review and test of reproducibility of subdecadal resolution palaeoenvironmental reconstructions from microfossil assemblages

Very high, even annual, resolution quantitative palaeoenvironmental reconstructions have been generated from microfossil assemblage data using transfer functions. Evidence of the utility of some of these reconstructions is given by the high correlations between the reconstructions and instrumental records. Such performance is despite several ecological and taphonomic issues that can become more problematic at subdecadal resolution than at multidecadal resolution. This paper explores these timescale dependent issues and tests the reproducibility of the several of published reconstructions. It demonstrates that the previously reported exceptionally good performance of several published chironomid-based reconstructions is not reproducible.publishedVersio

Determinants of Childhood Adiposity: Evidence from the Australian LOOK Study

To contribute to the current debate as to the relative influences of dietary intake and physical activity on the development of adiposity in community-based children.Participants were 734 boys and girls measured at age 8, 10 and 12 years for percent body fat (dual emission x-ray absorptiometry), physical activity (pedometers, accelerometers); and dietary intake (1 and 2-day records), with assessments of pubertal development and socioeconomic status.Cross-sectional relationships revealed that boys and girls with higher percent body fat were less physically active, both in terms of steps per day and moderate and vigorous physical activity (both sexes p<0.001 for both measures). However, fatter children did not consume more energy, fat, carbohydrate or sugar; boys with higher percent body fat actually consumed less carbohydrate (p = 0.01) and energy (p = 0.05). Longitudinal analysis (combined data from both sexes) was weaker, but supported the cross-sectional findings, showing that children who reduced their PA over the four years increased their percent body fat (p = 0.04). Relationships in the 8 year-olds and also in the leanest quartile of all children, where adiposity-related underreporting was unlikely, were consistent with those of the whole group, indicating that underreporting did not influence our findings.These data provide support for the premise that physical activity is the main source of variation in the percent body fat of healthy community-based Australian children. General community strategies involving dietary intake and physical activity to combat childhood obesity may benefit by making physical activity the foremost focus of attention

Determinants of Childhood Adiposity: Evidence from the Australian LOOK Study

BACKGROUND To contribute to the current debate as to the relative influences of dietary intake and physical activity on the development of adiposity in community-based children. METHODS Participants were 734 boys and girls measured at age 8, 10 and 12 years for percent body fat (dual emission x-ray absorptiometry), physical activity (pedometers, accelerometers); and dietary intake (1 and 2-day records), with assessments of pubertal development and socioeconomic status. RESULTS Cross-sectional relationships revealed that boys and girls with higher percent body fat were less physically active, both in terms of steps per day and moderate and vigorous physical activity (both sexes p<0.001 for both measures). However, fatter children did not consume more energy, fat, carbohydrate or sugar; boys with higher percent body fat actually consumed less carbohydrate (p = 0.01) and energy (p = 0.05). Longitudinal analysis (combined data from both sexes) was weaker, but supported the cross-sectional findings, showing that children who reduced their PA over the four years increased their percent body fat (p = 0.04). Relationships in the 8 year-olds and also in the leanest quartile of all children, where adiposity-related underreporting was unlikely, were consistent with those of the whole group, indicating that underreporting did not influence our findings. CONCLUSIONS These data provide support for the premise that physical activity is the main source of variation in the percent body fat of healthy community-based Australian children. General community strategies involving dietary intake and physical activity to combat childhood obesity may benefit by making physical activity the foremost focus of attention.The financial support provided by the Commonwealth Education Trust (London, UK) was vital to the completion of this work, and the authors thank the Board of Trustees for supporting them over several years. The authors also thank members of The Canberra Hospital Salaried Staff Specialists Private Practice Fund for their financial contribution to the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The Physical Chemistry of pMDI Formulations Derived from Hydrofluoroalkane Propellants. A Study of the Physical Behaviour of Poorly Soluble Active Pharmaceutical Ingredients; Bespoke Analytical Method Development Leading to Novel Formulation Approaches for Product Development.

Embargoed until July 2016.Active Pharmaceutical Ingredients (APIs) are frequently prepared for delivery to the lung for local topical treatment of diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, or for systemic delivery. One of the most commonly used devices for this purpose is the pressurised metered dose inhaler (pMDI) whereby drugs are formulated in a volatile propellant held under pressure. The compound is aerosolised to a respirably sized dose on actuation, subsequently breathed in by the user. The use of hydrofluoroalkanes (HFAs) in pMDIs since the Montreal Protocol initiated a move away from chlorofluorocarbon (CFC) based devices has resulted in better performing products, with increased lung deposition and a concomitant reduction in oropharyngeal deposition. The physical properties of HFA propellants are however poorly understood and their capacity for solubilising inhaled pharmaceutical products (IPPs) and excipients used historically in CFCs differ significantly. There is therefore a drive to establish methodologies to study these systems in-situ and post actuation to adequately direct formulation strategies for the production of stable and efficacious suspension and solution based products. Characterisation methods have been applied to pMDI dosage systems to gain insight into solubility in HFAs and to determine forms of solid deposits after actuation. A novel quantitative nuclear magnetic resonance method to investigate the physical chemistry of IPPs in these preparations has formed the centrepiece to these studies, accessing solubility data in-situ and at pressure for the first time in HFA propellants. Variable temperature NMR has provided thermodynamic data through van’t Hoff approaches. The methods have been developed and validated using budesonide to provide limits of determination as low as 1 μg/mL and extended to 11 IPPs chosen to represent currently prescribed inhaled corticosteroids (ICS), β2-adrenoagonists and antimuscarinic bronchodilators, and have highlighted solubility variations between the classes of compounds with lipophilic ICSs showing the highest, and hydrophilic β2- agonist / antimuscarinics showing the lowest solubilities from the compounds under study. To determine solid forms on deposition, a series of methods are also described using modified impaction methods in combination with analytical approaches including spectroscopy (μ-Raman), X-ray diffraction, SEM, chromatography and thermal analysis. Their application has ascertained (i) physical form / morphology data on commercial pMDI formulations of the ICS beclomethasone dipropionate (QVAR® / Sanasthmax®, Chiesi) and (ii) distribution assessment in-vitro of ICS / β2-agonist compounds from combination pMDIs confirming co-deposition (Seretide® / Symbicort®, GlaxoSmithKline / AstraZeneca). In combination, these methods provide a platform for development of new formulations based on HFA propellants. The methods have been applied to a number of ‘real’ systems incorporating derivatised cyclodextrins and the co-solvent ethanol, and provide a basis for a comprehensive study of solubilisation of the ICS budesonide in HFA134a using two approaches: mixed solvents and complexation. These new systems provide a novel approach to deliver to the lung, with reduced aerodynamic particle size distribution (APSD) potentially accessing areas suitable for delivery to peripheral areas of the lung (ICS) or to promote systemic delivery

Longitudinal patterns of physical activity in children aged 8 to 12 years: the LOOK study

BACKGROUND Data on longitudinal monitoring of daily physical activity (PA) patterns in youth over successive years is scarce but may provide valuable information for intervention strategies aiming to promote PA. METHODS Participants were 853 children (starting age ~8 years) recruited from 29 Australian elementary schools. Pedometers were worn for a 7-day period each year over 5 consecutive years to assess PA volume (steps per day) and accelerometers were worn concurrently in the final 2 years to assess PA volume (accelerometer counts (AC) per day), moderate and vigorous PA (MVPA), light PA (LPA) and sedentary time (SED). A general linear mixed model was used to examine daily and yearly patterns. RESULTS A consistent daily pattern of pedometer step counts, AC, MVPA and LPA emerged during each year, characterised by increases on school days from Monday to Friday followed by a decrease on the weekend. Friday was the most active and Sunday the least active day. The percentage of girls and boys meeting international recommendations of 11,000 and 13,000 steps/day respectively on a Monday, Friday and Sunday were 36%, 50%, 21% for boys and 35%, 45%, 18% for girls. The equivalent percentages meeting the recommended MVPA of >60 min/day on these days were 29%, 39%, 16% for boys and 15%, 21%, 10% for girls. Over the 5 years, boys were more active than girls (mean steps/day of 10,506 vs 8,750; p<0.001) and spent more time in MVPA (mean of 42.8 vs 31.1 min/day; p<0.001). Although there was little evidence of any upward or downward trend in steps/day from age 8 to 12 years, there was a trend toward lower MVPA, LPA and a corresponding increase in SED from age 11 to 12 years. CONCLUSION A weekly pattern of PA occurred in children as young as age 8 on a day by day basis; these patterns persisting through to age 12. In addition to supporting previous evidence of insufficient PA in children, our data, in identifying the level and incidence of insufficiency on each day of the week, may assist in the development of more specific strategies to increase PA in community based children

Longitudinal patterns of physical activity in children aged 8 to 12 years: The LOOK study

BACKGROUND: Data on longitudinal monitoring of daily physical activity (PA) patterns in youth over successive years is scarce but may provide valuable information for intervention strategies aiming to promote PA. METHODS: Participants were 853 children (starting age ~8 years) recruited from 29 Australian elementary schools. Pedometers were worn for a 7-day period each year over 5 consecutive years to assess PA volume (steps per day) and accelerometers were worn concurrently in the final 2 years to assess PA volume (accelerometer counts (AC) per day), moderate and vigorous PA (MVPA), light PA (LPA) and sedentary time (SED). A general linear mixed model was used to examine daily and yearly patterns. RESULTS: A consistent daily pattern of pedometer step counts, AC, MVPA and LPA emerged during each year, characterised by increases on school days from Monday to Friday followed by a decrease on the weekend. Friday was the most active and Sunday the least active day. The percentage of girls and boys meeting international recommendations of 11,000 and 13,000 steps/day respectively on a Monday, Friday and Sunday were 36%, 50%, 21% for boys and 35%, 45%, 18% for girls. The equivalent percentages meeting the recommended MVPA of >60 min/day on these days were 29%, 39%, 16% for boys and 15%, 21%, 10% for girls. Over the 5 years, boys were more active than girls (mean steps/day of 10,506 vs 8,750; p<0.001) and spent more time in MVPA (mean of 42.8 vs 31.1 min/day; p<0.001). Although there was little evidence of any upward or downward trend in steps/day from age 8 to 12 years, there was a trend toward lower MVPA, LPA and a corresponding increase in SED from age 11 to 12 years. CONCLUSION: A weekly pattern of PA occurred in children as young as age 8 on a day by day basis; these patterns persisting through to age 12. In addition to supporting previous evidence of insufficient PA in children, our data, in identifying the level and incidence of insufficiency on each day of the week, may assist in the development of more specific strategies to increase PA in community based children

Physical Education and Blood Lipid Concentrations in Children: The LOOK Randomized Cluster Trial

BACKGROUND AND OBJECTIVES Elevated blood lipids during childhood are predictive of dyslipidemia in adults. Although obese and inactive children have elevated values, any potentially protective role of elementary school physical education is unknown. Our objective was to determine the effect of a modern elementary school physical education (PE) program on the blood lipid concentrations in community-based children. METHODS In this cluster-randomized controlled trial, 708 healthy children (8.1±0.3 years, 367 boys) in 29 schools were allocated to either a 4-year intervention program of specialist-taught PE (13 schools) or to a control group of the currently practiced PE conducted by generalist classroom teachers. Fasting blood lipids were measured at ages 8, 10, and 12 years and intervention and control class activities were recorded. RESULTS Intervention classes included more fitness work and more moderate and vigorous physical activity than control classes (both p3.36mmol.L(-1),130 mg/dL) was lower in the intervention than control group (14% vs. 23%, p = 0.02). There was also an intervention effect on mean LDL-C across all boys (reduction of 9.6% for intervention v 2.8% control, p = 0.02), but not girls (p = 0.2). The intervention effect on total cholesterol mirrored LDL-C, but there were no detectable 4-year intervention effects on high-density lipoprotein cholesterol or triglycerides. CONCLUSIONS The PE program delivered by specialist teachers over four years in elementary school reduced the incidence of elevated LDL-C in boys and girls, and provides a means by which early preventative practices can be offered to all children. TRIAL REGISTRATION Australia New Zealand Clinical Trial Registry ANZRN12612000027819 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347799.Sources of funding were The Commonwealth Education Trust (New Zealand House, London, UK) (http://www.commonwealth.org.uk/) and the Canberra Hospital Salaried Staff Specialists Fund (http://healthresearch.anu.edu.au/documents/PPFVACATION/ppf-major-info-2012.pdf). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Low physical activity and obesity: causes of chronic disease or simply predictors

. Background and Purpose: Many studies have shown associations between risk of morbidity and mortality with both obesity and low physical activity (PA), but association does not imply causality. Moreover, there is an inverse relationship between PA and obesity; therefore, controlling for one of these factors when investigating the risk associated with the other is essential. The purpose of this review is to determine whether low PA and obesity actually cause metabolic dysfunction and chronic disease, especially type 2 diabetes (T2D), rather than simply operating as predictors or markers. Methods: The case for causality is strengthened if the following two conditions are satisfied: first, that significant associations between obesity or low PA and risk persist after controlling appropriately; and second, that the physiological mechanisms by which obesity or low PA may exert a causal effect are clearly established. The studies examined include those that have used cardiorespiratory (CR) fitness as a surrogate measure for PA, thus also providing evidence for low CR fitness as an independent risk factor in its own right. Results and Conclusions: Low PA and poor CR fitness are independent predictors of mortality related to type 2 diabetes and chronic disease in general. Together with welldemonstrated mechanisms, there is strong evidence that low PA and low CR fitness are direct, independent causes of metabolic dysfunction and type 2 diabetes. Despite some reports to the contrary, there is evidence that both general and visceral obesity are predictors of mortality and morbidity after controlling for PA. However, in the absence of established mechanisms, evidence is insufficient to conclude that either general or visceral obesity is a direct, independent cause of metabolic dysfunction or type 2 diabetes