Cycling in São Paulo, Brazil (1997-2012): Correlates, time trends and health consequences

The purpose of the study was to describe cyclists and cycling trips, and to explore correlates, time trends and health consequences of cycling in São Paulo, Brazil from 1997 to 2012. Cross-sectional analysis using repeated São Paulo Household Travel Surveys (HTS). At all time periods cycling was a minority travel mode in São Paulo (1174 people with cycling trips out of 214,719 people). Poisson regressions for individual correlates were estimated using the entire 2012 HTS sample. Men were six times more likely to cycle than women. We found rates of bicycle use rising over time among the richest quartile but total cycling rates dropped from 1997 to 2012 due to decreasing rates among the poor. Harms from air pollution would negate benefits from physical activity through cycling only at 1997 air pollution levels and at very high cycling levels (≥ 9 h of cycling per day). Exposure-based road injury risk decreased between 2007 and 2012, from 0.76 to 0.56 cyclist deaths per 1000 person-hours travelled. Policies to reduce spatial segregation, measures to tackle air pollution, improvements in dedicated cycling infrastructure, and integrating the bicycle with the public transport system in neighborhoods of all income levels could make cycling safer and prevent more individuals from abandoning the cycling mode in São Paulo.THS acknowledges funding from the Brazilian Science without Borders Scheme (Process number: 200358/2014-6) and the Sao Paulo Research Foundation (Process number: 2012/08565-4). ACD received a postdoctoral research fellowship from the Brazilian National Council for Scientific and Technological Development (249038/2013-7). MT and JW: The work was undertaken by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust (MR/K023187/1), under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged

Global inequalities in the double burden of malnutrition and associations with globalisation: a multilevel analysis of Demographic and Health Surveys from 55 low-income and middle-income countries, 1992-2018

BACKGROUND: Low-income and middle-income countries (LMICs) face a double burden of malnutrition (DBM), whereby overnutrition and undernutrition coexist within the same individual, household, or population. This analysis investigates global inequalities in household-level DBM, expressed as a stunted child with an overweight mother, and its association with economic, social, and political globalisation across country income and household wealth. METHODS: We pooled anthropometric and demographic data for 1 132 069 children (aged <5 years) and their mothers (aged 15-49 years) from 189 Demographic and Health Surveys in 55 LMICs between 1992 and 2018. These data were combined with country-level data on economic, social, and political globalisation from the Konjunkturforschungsstelle Globalisation Index and gross national income (GNI) from the World Bank. Multivariate associations between DBM and household wealth, GNI, and globalisation and their interactions were tested using multilevel logistic regression models with country and year fixed-effects and robust standard errors clustered by country. FINDINGS: The probability of DBM was higher among richer households in poorer LMICs and poorer households in richer LMICs. Economic globalisation was associated with higher odds of DBM among the poorest households (odds ratio 1·49, 95% CI 1·20-1·86) compared with the richest households. These associations attenuated as GNI increased. Social globalisation was associated with higher odds of DBM (1·39, 95% CI 1·16-1·65), independently of household wealth or country income. No associations were identified between political globalisation and DBM. INTERPRETATION: Increases in economic and social globalisation were associated with higher DBM, although the impacts of economic globalisation were mostly realised by the world's poorest. The economic patterning of DBM observed in this study calls for subpopulation-specific double-duty actions, which should further aim to mitigate the potential negative and unequal impacts of globalisation. FUNDING: UK Biotechnology and Biological Sciences Research Council. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section

Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia

Parkinson disease (PD) is a progressive, neurodegenerative disorder affecting over 6.1 million people worldwide. Although the cause of PD remains unclear, studies of highly penetrant mutations identified in early-onset familial parkinsonism have contributed to our understanding of the molecular mechanisms underlying disease pathology. Dopamine (DA) transporter (DAT) deficiency syndrome (DTDS) is a distinct type of infantile parkinsonism-dystonia that shares key clinical features with PD, including motor deficits (progressive bradykinesia, tremor, hypomimia) and altered DA neurotransmission. Here, we define structural, functional, and behavioral consequences of a Cys substitution at R445 in human DAT (hDAT R445C), identified in a patient with DTDS. We found that this R445 substitution disrupts a phylogenetically conserved intracellular (IC) network of interactions that compromise the hDAT IC gate. This is demonstrated by both Rosetta molecular modeling and fine-grained simulations using hDAT R445C, as well as EPR analysis and X-ray crystallography of the bacterial homolog leucine transporter. Notably, the disruption of this IC network of interactions supported a channel-like intermediate of hDAT and compromised hDAT function. We demonstrate that Drosophila melanogaster expressing hDAT R445C show impaired hDAT activity, which is associated with DA dysfunction in isolated brains and with abnormal behaviors monitored at high-speed time resolution. We show that hDAT R445C Drosophila exhibit motor deficits, lack of motor coordination (i.e. flight coordination) and phenotypic heterogeneity in these behaviors that is typically associated with DTDS and PD. These behaviors are linked with altered dopaminergic signaling stemming from loss of DA neurons and decreased DA availability. We rescued flight coordination with chloroquine, a lysosomal inhibitor that enhanced DAT expression in a heterologous expression system. Together, these studies shed some light on how a DTDS-linked DAT mutation underlies DA dysfunction and, possibly, clinical phenotypes shared by DTDS and PD

Does Uptake of Pharmaceuticals Vary Across Earthworm Species?

This study compared the uptake and depuration of four commonly used pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in two earthworm species (Lumbricus terrestris and Eisenia fetida). L. terrestris are a larger species and often found in deep burrows whereas E. fetida prefer to reside near the soil surface. Species burrowing habits and sizes may alter uptake by earthworms. All four pharmaceuticals were taken up into both L. terrestris and E. fetida tissue after 21 days exposure to spiked soil. Bioconcentration factors (BCFs) ranged between 1.72 and 29.83 for L. terrestris and 1.14 and 63.03 for E. fetida. For carbamazepine and diclofenac, BCFs were similar whereas for fluoxetine and orlistat, BCFs in E. fetida were more than double those seen in L. terrestris. Results indicate that uptake into earthworms cannot be generalised between species and that the influence of species traits can vary depending on the nature of the study chemical

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

Objectives Decreased thyroid volume has been related to increased prevalence of thyroid cancer.Subjects and methods One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63).Results Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%).Conclusions Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Funded by Asthma UK grant number 09/ 36

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT