Hypothesis: The electrochemical regulation of metabolism

Abstract -An Electrochemical model of metabolism is described that takes account of a variety of metabolic phenomena observed in our laboratory. These include a utilisation by hepatocytes of oxygen, substantially in excess of ATP requirements; energydependence of the [lactate~[pyruvate] ratio; non-equilibrium behaviour of the components of the lactate dehydrogenase reaction during ethanol oxidation, and linear relationships between cellular potentials and metabolic fluxes. In the light of these findings, we propose as an extension of the Mitchell chemiosmotic hypothesis, that metabolic pathways are under the control of opposing far-from-equilibrium chemical and electrical forces that poise the pathways in a balanced state of apparent equilibrium, allowing flux to be regulated by changes in the magnitude of cellular potentials

Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial

for the LIMIT Randomised Trial GroupOBJECTIVE To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women. DESIGN Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital. SETTING Three public maternity hospitals across South Australia. PARTICIPANTS 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks’ gestation, and BMI ≥25. INTERVENTIONS 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information. MAIN OUTCOME MEASURES Incidence of infants born large for gestational age (birth weight ≥90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles. RESULTS 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups. CONCLUSIONS For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).Jodie M Dodd, Deborah Turnbull, Andrew J McPhee, Andrea R Deussen, Rosalie M Grivell, Lisa N Yelland, Caroline A Crowther, Gary Wittert, Julie A Owens, and Jeffrey S Robinso

Probing Planckian physics: resonant production of particles during inflation and features in the primordial power spectrum

The phenomenon of resonant production of particles {\it after} inflation has received much attention in the past few years. In a new application of resonant production of particles, we consider the effect of a resonance {\em during} inflation. We show that if the inflaton is coupled to a massive particle, resonant production of the particle during inflation modifies the evolution of the inflaton, and may leave an imprint in the form of sharp features in the primordial power spectrum. Precision measurements of microwave background anisotropies and large-scale structure surveys could be sensitive to the features, and probe the spectrum of particles as massive as the Planck scale.Comment: 19 pages, 11 eps figure

The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial

Background: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10+0-20+0weeks, and BMI ≥ 25 kg/m2were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. Results: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group 11261.19±14573.97 versus Standard Care Group 11306.70±14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to$45,000. Conclusions: Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial

BACKGROUND: Overweight and obesity during pregnancy represents a considerable health burden. While research has focused on interventions to limit gestational weight gain, there is little information describing their impact on neonatal health. Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese. METHODS: We report a range of pre-specified secondary neonatal outcomes from a large randomised trial in which antenatal dietary and lifestyle advice was provided to women who were overweight or obese. Pregnant women were eligible for participation with a body mass index of 25 kg/m(2) or over, and singleton gestation between 10(+0) and 20(+0) weeks. Outcome measures included gestational age at birth; Apgar score below 7 at 5 minutes of age; need for resuscitation at birth; birth weight above 4.5 kg or below 2.5 kg; birth weight, length and head circumference (and Z-scores); admission to the nursery; respiratory distress syndrome; and postnatal length of stay. Data relating to the primary outcome (large for gestational age infants defined as birth weight above the 90th centile) and birth weight above 4 kg have been reported previously. Analyses used intention-to-treat principles. RESULTS: In total, 2,142 infants were included in the analyses. Infants born to women following lifestyle advice were significantly less likely to have birth weight above 4.5 kg (2.15% versus 3.69%; adjusted risk ratio (aRR)=0.59; 95% confidence interval (CI) 0.36 to 0.98; P=0.04), or respiratory distress syndrome (1.22% versus 2.57%; aRR=0.47; 95% CI 0.24 to 0.90; P=0.02), particularly moderate or severe disease, and had a shorter length of postnatal hospital stay (3.94±7.26 days versus 4.41±9.87 days; adjusted ratio of means 0.89; 95% CI 0.82 to 0.97; P=0.006) compared with infants born to women who received Standard Care. CONCLUSIONS: For women who are overweight or obese, antenatal dietary and lifestyle advice has health benefits for infants, without an increase in the risk of harm. Continued follow-up into childhood will be important to assess the longer-term effects of a reduction in high infant birth weight on risk of child obesity. Please see related articles: http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/201 . CLINICAL TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 )

Density and Graviton Perturbations in the Cosmic Microwave Background

This paper evaluates and compares the gravitational wave and density perturbation contributions to the cosmic microwave background radiation, on the basis of the same power law inflationary model. The inflation to radiation transition is treated as instantaneous, but a model is constructed to allow for a smooth transition from the radiation to the matter dominated eras. The equations are numerically investigated and integrated, without any basic approximations being made. Use is made of the synchronous gauge, with appropriate gauge invariant variables, thus eliminating any confusion arising from unphysical gauge modes. We find a non- negligible gravitational wave contribution, which becomes dominant for a power law expansion with exponent $q < 13$. We also explore the dependence of our results with the main characteristic of the transition region, its length.Comment: 19 page

Inflationary perturbations near horizon crossing

We study the behaviour of inflationary density perturbations in the vicinity of horizon crossing, using numerical evolution of the relevant mode equations. We explore two specific scenarios. In one, inflation is temporarily ended because a portion of the potential is too steep to support inflation. We find that perturbations on super-horizon scales can be modified, usually leading to a large amplification, because of entropy perturbations in the scalar field. This leads to a broad feature in the power spectrum, and the slow-roll and Stewart--Lyth approximations, which assume the perturbations reach an asymptotic regime well outside the horizon, can fail by many orders of magnitude in this regime. In the second scenario we consider perturbations generated right at the end of inflation, which re-enter shortly after inflation ends --- such perturbations can be relevant for primordial black hole formation.Comment: 7 pages RevTeX file with six figures incorporated. Minor changes to match published versio

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial

BACKGROUND Overweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity. METHODS We conducted a randomised controlled trial, in which pregnant women with a body mass index ?25 kg/m2, and singleton gestation between 10+0 to 20+0 weeks were recruited and randomised to Lifestyle Advice (involving a comprehensive dietary and lifestyle intervention over their pregnancy) or Standard Care. Within the intervention group, we conducted a nested randomised trial in which a subgroup of women were further randomised to receive access to supervised group walking sessions in addition to the standard information presented during the intervention contacts (the Walking group) or standard information only. The outcome measures were maternal dietary intake, (including food groups, macronutrient and micronutrient intake, diet quality (using the Healthy Eating Index; HEI), dietary glycaemic load, and glycaemic index) and maternal physical activity. Women completed the Harvard Semi-Structured Food Frequency Questionnaire, and the Short Questionnaire to Assess Health-enhancing Physical Activity (SQUASH), at trial entry, 28 and 36 weeks¿ gestational age, and 4 months postpartum. Analyses were performed on an intention-to-treat basis, using linear mixed effects models with adjustment for the stratification variables. RESULTS Women randomised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day, as well as increased consumption of fibre, and reduced percentage energy intake from saturated fats (P?<?0.05 for all). Maternal HEI was significantly improved at both 28 (73.35?±?6.62 versus 71.86?±?7.01; adjusted difference in means 1.58; 95% CI 0.89 to 2.27; P?<?0.0001) and 36 (72.95?±?6.82 versus 71.17?±?7.69; adjusted difference in means 1.77; 95% CI 1.01 to 2.53; P?<?0.0001) weeks. There were no differences in dietary glycaemic index or glycaemic load. Women randomised to Lifestyle Advice also demonstrated greater total physical activity (adjusted difference in means 359.76 metabolic equivalent task units (MET) minutes/week; 95% CI 74.87 to 644.65; P?=?0.01) compared with women receiving Standard Care. The supervised walking group was poorly utilised. CONCLUSIONS For women who are overweight or obese, antenatal lifestyle advice improves maternal diet and physical activity during pregnancy. Please see related articles: http://www.biomedcentral.com/1741-7015/12/163 and http://www.biomedcentral.com/1741-7015/12/201. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry (http://ACTRN12607000161426)Jodie M Dodd, Courtney Cramp, Zhixian Sui, Lisa N Yelland, Andrea R Deussen, Rosalie M Grivell, Lisa J Moran, Caroline A Crowther, Deborah Turnbull, Andrew J McPhee, Gary Wittert, Julie A Owens, Jeffrey S Robinso