Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD)

Vitamin D is an essential nutrient that is metabolized in the body to generate an active metabolite (1, 25(OH)2D) with hormone-like activity and highly diverse roles in cellular function. Vitamin D deficiency (VDD) is a prevalent but easily p reventable nutritional disturbance. Emerging evidence demonstrates the importance of s ufficient vitamin D concentrations during fetal life with deficiencies leading to long-term effects into adulthood. Here, we provide a detailed review and perspective of evidence for the role of maternal VDD in offspring long-term health, particularly as it relates to developmental origins of health and disease (DOHaD). We focus on the roles in neurobehavioral and cardiometabolic disorders in humans and highlight recent finding s from zebrafish and rodent models that probe potential mechanisms linking early life VDD to later life health outcomes. Moreover, we explore evidence implicating epigenetic mechanisms as a mediator of this link. Gaps in our current understanding of how maternal VDD might result in deleterious offspring outcomes later in life are also addressed

What Can WMAP Tell Us About The Very Early Universe? New Physics as an Explanation of Suppressed Large Scale Power and Running Spectral Index

The Wilkinson Microwave Anisotropy Probe microwave background data may be giving us clues about new physics at the transition from a ``stringy'' epoch of the universe to the standard Friedmann Robertson Walker description. Deviations on large angular scales of the data, as compared to theoretical expectations, as well as running of the spectral index of density perturbations, can be explained by new physics whose scale is set by the height of an inflationary potential. As examples of possible signatures for this new physics, we study the cosmic microwave background spectrum for two string inspired models: 1) modifications to the Friedmann equations and 2) velocity dependent potentials. The suppression of low ``l'' modes in the microwave background data arises due to the new physics. In addition, the spectral index is red (n<1) on small scales and blue (n>1) on large scales, in agreement with data.Comment: 18 pages, 2 figures, submitted for publication in Physical Review D, references added in this versio

Multiple Interactions and the Structure of Beam Remnants

Recent experimental data have established some of the basic features of multiple interactions in hadron-hadron collisions. The emphasis is therefore now shifting, to one of exploring more detailed aspects. Starting from a brief review of the current situation, a next-generation model is developed, wherein a detailed account is given of correlated flavour, colour, longitudinal and transverse momentum distributions, encompassing both the partons initiating perturbative interactions and the partons left in the beam remnants. Some of the main features are illustrated for the Tevatron and the LHC.Comment: 69pp, 33 figure

A new scoring system derived from base excess and platelet count at presentation predicts mortality in paediatric meningococcal sepsis

Introduction: The aim of this study was to derive a novel prognostic score for mortality in paediatric meningococcal sepsis (MS) based on readily available laboratory markers.Methods: A multicentre retrospective cohort study for the consortium set and a single centre retrospective study for replication set. The consortium set were 1,073 children (age 1 week to 17.9 years) referred over a 15-year period (1996 to 2011), who had an admission diagnosis of MS, referred to paediatric intensive care units (PICUs) in six different European centres. The consortium set was split into a development set and validation set to derive the score. The replication set were 134 children with MS (age 2 weeks to 16 years) referred over a 4-year period (2007 to 2011) to PICUs via the Children's Acute Transport Service (CATS), London.Results: A total of 85/1,073 (7.9%) children in the consortium set died. A total of 16/134 (11.9%) children in the replication set died. Children dying in the consortium set had significantly lower base excess, C-reactive protein (CRP), platelet and white cell count, more deranged coagulation and higher lactate than survivors. Paediatric risk of mortality (PRISM) score, Glasgow meningococcal septicaemia prognosis score (GMSPS) and Rotterdam score were also higher. Using the consortium set, a new scoring system using base excess and platelet count at presentation, termed the BEP score, was mathematically developed and validated. BEP predicted mortality with high sensitivity and specificity scores (area under the curve (AUC) in the validation set = 0.8

Plasma lipid profiles discriminate bacterial from viral infection in febrile children.

Funder: NIHR Imperial BRCFever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

Emission of carbon monoxide, total hydrocarbons and particulate matter during wood combustion in a stove operating under distinct conditions

Wood combustion experiments were carried out to determine the effect of ignition technique, biomass load and cleavage, as well as secondary air supply, on carbon monoxide (CO), total hydrocarbon (THC), particulate matter (PM10) and particle number emissions fromawoodstove.Wood fromtwo typical tree species in the Iberian Peninsula was selected: pine (Pinus pinaster) and beech (Fagus sylvatica). The highest CO and total hydrocarbon emission factors (EFs) were observed, respectively, for pine and beech, for high and low fuel loads. The highest PM10 EFwas recorded for the operationwith lowloads for bothwoods. Secondary air supply produced the lowest PM10 emission factors. The top ignition can decrease the PM10 EF to less than halfwhen compared with the common technique of lighting from the bottom. The lowest particle number emission factors were observed when operating with high loads of split beech logs and when using secondary air supply during the combustion of pine. Regarding particle number distributions, the highest geometric mean diameter (Dg), for both woods, were observed when operating with high loads (with split and non-split wood)