Sleep duration in school-age children with epilepsy: A cross-sectional study

Background: Normal sleep is required for the optimal growth and development of the children. Ineffective or inadequate sleep is common in children with epilepsy. Objectives: The objectives of this study were to study the sleep duration and describe the factors affecting it in school-aged children with epilepsy attending the seizure clinic of a pediatric tertiary care hospital. Materials and Methods: 6–12-year-old children with epilepsy, attending the seizure clinic formed the study subjects. They were assessed for inclusion in the study using INCLEN diagnostic tool for epilepsy (INDT-Epi) to achieve a sample size of 139. Informed written consent was obtained from parents. Background sociodemographic information, seizure type and treatment details, and duration of sleep of the child were collected from the parents. The proportion of children with epilepsy who had sleep problems were expressed as percentage. Results: The mean age of study population was 9.07±2.09 years. The average sleep duration of the study population was 9.41±1.41 h. The mean nap time of the study population was 68.51±33.88 min. No significant association was seen among the factors that determine sleep duration. Conclusion: Children with epilepsy tend to sleep for lesser hours when compared to historic controls of normal school-age children reported in literature

Sense3

Sense3, at its core, is a game in which the player has to collectively use the three senses of sight, touch and hearing to primarily dodge obstacles and collect audio samples, which are vertically remixed to form music. We chose EDM themed music, coupled with a futuristic outer space theme for the art style of the game, creating an immersive environment. The game is a pseudo-endless runner, where the player has to collect all the components to assemble their music. After each play through, the game allows the player to listen to the newly assembled music before reloading. We wanted to encourage replay value as each play through yields new and different music. The concept was decided upon after a series of prototyping sessions and iterations on a select few of them

Canine Parvovirus Isolates of India and the Relevance of Canine Parvovirus Type-2 Vaccines

A study was conducted to characterise the field isolates of canine parvovirus (CPV) and an in vitro cross neutralisation assay was performed against the vaccinated dog sera. Out of 45 faecal samples processed for virus isolation, 27 samples showed cytopathic effect (CPE) at first passage, which were confirmed positive by CPV variant types specific PCR. The CPV type 2 was not detected in any of the clinical samples. Of these 27 positive samples only 23 samples showed CPE and were further confirmed as CPV by haemagglutination inhibition test, ELISA and immuno-chromatographic strip test. Antigenic typing performed using a panel of monoclonal antibodies revealed that four of the 23 isolates were CPV 2b type and the remaining 19 isolates were typed as CPV 2a. The antigenic typing results obtained using the monoclonal antibodies corroborated the sequencing results reported by our group earlier. The cross neutralization study with polyclonal sera revealed that the sera of original antigenic type CPV 2 can neutralize the antigenic variants 2a and 2b effectively. Thus we conclude that the vaccines containing CPV type 2 virus can be used to immunise the dogs against the prevalent CPV 2a and CPV 2b infection. A live virus challenge study in dogs may further confirm this observation

The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants.

BACKGROUND: Strategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function. METHODS: Infants 5weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5mg), probiotic (1010Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14weeks of age based on detection of VP6-specific IgA at ?20U/ml in previously seronegative infants or a fourfold rise in concentration. RESULTS: The study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): -1.4%, 16.2%), p=0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: -4.4%, 13.2%), p=0.272). 16 serious adverse events were recorded, none related to study interventions. CONCLUSIONS: Zinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation. TRIAL REGISTRATION: The trial was registered in India (CTRI/2012/05/002677)

Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Characteristics of Prediabetes, predictors of progression and strategies to prevent Type 2 Diabetes Mellitus in a multiethnic population in the United Kingdom

Executive Summary: Type 2 Diabetes Mellitus (T2DM) is a chronic multi factorial disorder linked to obesity that is associated with increased morbidity and mortality. T2DM poses a major public health problem with the prevalence expecting to reach 4 million in the United Kingdom by the year 2025. Upto 50% of people may have established complications at the time of diagnosis of T2DM. However, T2DM is preceded by a latent phase of Prediabetes (PDM) which provides a window of opportunity for primary prevention. PDM is often known as impaired glucose metabolism (IGM) or impaired glucose regulation (IGR). PDM is a collective term for impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and those with combined IFG and IGT. The reported prevalence of these conditions is variable throughout the world. This thesis seeks to address key questions on identification of IGR, determine factors predicting progression to T2DM and thus propose prevention strategies in a mixed ethnic population in the UK using data from the ADDITION Leicester and ADDITION PLUS studies. ADDITION Leicester is a sub study of the multinational multi centre study-ADDITION Europe. ADDITION study is a randomised controlled trial evaluating the benefits of a multi factorial cardiovascular disease risk factor intervention in a cohort of patients with screen detected T2DM. The prevalence of PDM was 16% in the study population with IFG, IGT and combined IFG and IGT being 2.8%, 11% and 2.2% respectively. People of South Asian (SA) origin have a significantly higher adjusted prevalence of PDM compared to those of White European (WE) origin (OR: 1.57; 95% CI: 1.24 to 1.98). A risk score tailored to the local population (Leicester risk assessment score) was robust in identifying those at risk of developing T2DM and PDM as well those progressing from PDM to T2DM at 12 months. Subjects with PDM have a unique phenotype placing their cardiovascular disease (CVD) risks between T2DM and normal glucose tolerance. Novel markers of CVD such as Interleukin 6, Adiponectin, Leptin and C-reactive protein are also raised in those with PDM compared to normal. The risk of progression from PDM to T2DM at 12 months is higher for SA compared to WE (OR: 3.09, 95% CI- 1.58 to 6.02). The diabetes progression rate (cases/100 person-years) for IFG, IGT and combined IFG and IGT were 5.51, 3.13 and 14.46 respectively. The risk of progression for SA people occurs at a lower cut off for BMI and waist circumference. A meta analysis of 13,314 patients from 22 studies with PDM revealed a pooled progression rate (cases per 100 person-years) (95% CI) to be 6.29 (4.29- 9.22), 7.48 (5.00-11.18) and 7.86 (5.51- 11.20) for people with IFG, IGT and combined IFG+IGT respectively. Presence of CVD, central obesity measured both by waist circumference and BMI, triglycerides, fasting plasma glucose (FPG) and HbA1c significantly predict progression to T2DM at 12 months. Presence of metabolic syndrome with more than 2 additional criteria significantly predicts progression to T2DM. In terms of adipocytokines, TNFα is the only marker, after adjusting for confounders that is significantly associated with progression to T2DM. In terms of follow up of this cohort, we propose a two step method using FPG >6 mmol/L as a screening tool to identify people who can subsequently be screened using an OGTT, reducing the number of OGTT needed to 23.5%. Our findings suggest using a structured screening programme with a risk score used in parallel to the recommended opportunistic screening for T2DM. The need for ethnic specific cut-off for obesity has been established. Factors such as presence of metabolic syndrome, HbA1c >6%, presence of a single diabetes range glucose value and pre-existing CVD may be used in risk stratification of individuals with PDM. These factors may also be used to guide those who may benefit from Metformin in addition to established life style interventions for PDM. Our findings provide a contemporary and prospective data on the prevalence of PDM in a multi ethnic UK population and factors predicting progression from PDM to T2DM. A robust strategy using a self assessed risk score is proposed to identify those at risk of developing PDM and T2DM. A step wise ethnic specific algorithm using anthropometric measures is also recommended to enable follow up of those with PDM. These findings have important implications for public health in informing strategies to address the emerging pandemic of T2DM

Characteristics of prediabetes, predictors of progression and strategies to prevent Type 2 Diabetes Mellitus in a multiethnic population in the United Kingdom

Executive Summary: Type 2 Diabetes Mellitus (T2DM) is a chronic multi factorial disorder linked to obesity that is associated with increased morbidity and mortality. T2DM poses a major public health problem with the prevalence expecting to reach 4 million in the United Kingdom by the year 2025. Upto 50% of people may have established complications at the time of diagnosis of T2DM. However, T2DM is preceded by a latent phase of Prediabetes (PDM) which provides a window of opportunity for primary prevention. PDM is often known as impaired glucose metabolism (IGM) or impaired glucose regulation (IGR). PDM is a collective term for impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and those with combined IFG and IGT. The reported prevalence of these conditions is variable throughout the world. This thesis seeks to address key questions on identification of IGR, determine factors predicting progression to T2DM and thus propose prevention strategies in a mixed ethnic population in the UK using data from the ADDITION Leicester and ADDITION PLUS studies. ADDITION Leicester is a sub study of the multinational multi centre study-ADDITION Europe. ADDITION study is a randomised controlled trial evaluating the benefits of a multi factorial cardiovascular disease risk factor intervention in a cohort of patients with screen detected T2DM. The prevalence of PDM was 16% in the study population with IFG, IGT and combined IFG and IGT being 2.8%, 11% and 2.2% respectively. People of South Asian (SA) origin have a significantly higher adjusted prevalence of PDM compared to those of White European (WE) origin (OR: 1.57; 95% CI: 1.24 to 1.98). A risk score tailored to the local population (Leicester risk assessment score) was robust in identifying those at risk of developing T2DM and PDM as well those progressing from PDM to T2DM at 12 months. Subjects with PDM have a unique phenotype placing their cardiovascular disease (CVD) risks between T2DM and normal glucose tolerance. Novel markers of CVD such as Interleukin 6, Adiponectin, Leptin and C-reactive protein are also raised in those with PDM compared to normal. The risk of progression from PDM to T2DM at 12 months is higher for SA compared to WE (OR: 3.09, 95% CI- 1.58 to 6.02). The diabetes progression rate (cases/100 person-years) for IFG, IGT and combined IFG and IGT were 5.51, 3.13 and 14.46 respectively. The risk of progression for SA people occurs at a lower cut off for BMI and waist circumference. A meta analysis of 13,314 patients from 22 studies with PDM revealed a pooled progression rate (cases per 100 person-years) (95% CI) to be 6.29 (4.29- 9.22), 7.48 (5.00-11.18) and 7.86 (5.51- 11.20) for people with IFG, IGT and combined IFG+IGT respectively. Presence of CVD, central obesity measured both by waist circumference and BMI, triglycerides, fasting plasma glucose (FPG) and HbA1c significantly predict progression to T2DM at 12 months. Presence of metabolic syndrome with more than 2 additional criteria significantly predicts progression to T2DM. In terms of adipocytokines, TNFα is the only marker, after adjusting for confounders that is significantly associated with progression to T2DM. In terms of follow up of this cohort, we propose a two step method using FPG >6 mmol/L as a screening tool to identify people who can subsequently be screened using an OGTT, reducing the number of OGTT needed to 23.5%. Our findings suggest using a structured screening programme with a risk score used in parallel to the recommended opportunistic screening for T2DM. The need for ethnic specific cut-off for obesity has been established. Factors such as presence of metabolic syndrome, HbA1c >6%, presence of a single diabetes range glucose value and pre-existing CVD may be used in risk stratification of individuals with PDM. These factors may also be used to guide those who may benefit from Metformin in addition to established life style interventions for PDM. Our findings provide a contemporary and prospective data on the prevalence of PDM in a multi ethnic UK population and factors predicting progression from PDM to T2DM. A robust strategy using a self assessed risk score is proposed to identify those at risk of developing PDM and T2DM. A step wise ethnic specific algorithm using anthropometric measures is also recommended to enable follow up of those with PDM. These findings have important implications for public health in informing strategies to address the emerging pandemic of T2DM.EThOS - Electronic Theses Online ServiceGBUnited Kingdo