A hybrid intelligent agent for notification of users distracted by mobile phones in an urban environment

Mobile devices are now ubiquitous in daily life and the number of activities that can be performed using them is continually growing. This implies increased attention being placed on the device and diverted away from events taking place in the surrounding environment. The impact of using a smartphone on pedestrians in the vicinity of urban traffic has been investigated in a multimodal, fully immersive, virtual reality environment. Based on experimental data collected, an agent to improve the attention of users in such situations has been developed. The proposed agent uses explicit, contextual data from experimental conditions to feed a statistical learning model. The agent’s decision process is aimed at notifying users when they become unaware of critical events in their surroundings

Lack of HLA predominance and HLA shared epitopes in biliary Atresia

Biliary atresia (BA) is characterized by progressive inflammation and fibrosis of bile ducts. A theory of pathogenesis entails autoimmune-mediated injury targeting bile duct epithelia. One of the strongest genetic associations with autoimmunity is with HLA genes. In addition, apparently dissimilar HLA alleles may have similar antigen-binding sites, called shared epitopes, that overlap in their capacity to present antigens. In autoimmune disease, the incidence of the disease may be related to the presence of shared epitopes, not simply the HLA allelic association. Aim: To determine HLA allele frequency (high-resolution genotyping) and shared epitope associations in BA. Results: Analysis of every allele for HLA-A, -B, -C, -DRB1, -DPB1 and -DQB1 in 180 BA and 360 racially-matched controls did not identify any significant HLA association with BA. Furthermore, shared epitope analysis of greater than 10 million possible combinations of peptide sequences was not different between BA and controls. Conclusions: This study encompasses the largest HLA allele frequency analysis for BA in the United States and is the first study to perform shared epitope analysis. When controlling for multiple comparisons, no HLA allele or shared epitope association was identified in BA. Future studies of genetic links to BA that involve alterations of the immune response should include investigations into defects in regulatory T cells and non-HLA linked autoinflammatory diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-42) contains supplementary material, which is available to authorized users

Spinocerebellar ataxia type 17: Report of a family with reduced penetrance of an unstable Gln(49 )TBP allele, haplotype analysis supporting a founder effect for unstable alleles and comparative analysis of SCA17 genotypes

BACKGROUND: Spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder in man, is caused by an expanded polymorphic polyglutamine-encoding trinucleotide repeat in the gene for TATA-box binding protein (TBP), a main transcription factor. Observed pathogenic expansions ranged from 43 – 63 glutamine (Gln) codons (Gln(43–63)). Reduced penetrance is known for Gln(43–48 )alleles. In the vast majority of families with SCA17 an expanded CAG repeat interrupted by a CAA CAG CAA element is inherited stably. RESULTS: Here, we report the first pedigree with a Gln(49 )allele that is a) not interrupted, b) unstable upon transmission, and c) associated with reduced penetrance or very late age of onset. The 76-year-old father of two SCA17 patients carries the Gln(49 )TBP allele but presents without obvious neurological symptoms. His children with Gln(53 )and Gln(52 )developed ataxia at the age of 41 and 50. Haplotype analysis of this and a second family both with uninterrupted expanded and unstable pathological SCA17 alleles revealed a common core genotype not present in the interrupted expansion of an unrelated SCA17 patient. Review of the literature did not present instability in SCA17 families with expanded alleles interrupted by the CAA CAG CAA element. CONCLUSION: The presence of a Gln(49 )SCA17 allele in an asymptomatic 76-year-old male reams the discussion of reduced penetrance and genotypes producing very late disease onset. In SCA17, uninterrupted expanded alleles of TBP are associated with repeat instability and a common founder haplotype. This suggests for uninterrupted expanded alleles a mutation mechanism and some clinical genetic features distinct from those alleles interrupted by a CAA CAG CAA element

Preferences for menu labelling formats of young adults in Brazil and in the United Kingdom

Objective This pilot study was aimed at exploring preferences of young adults in two different contexts on restaurant menu labelling formats. Methods Five focus groups were conducted with 36 participants, two focus groups with 11 participants in Brazil and three focus groups with 25 in the United Kingdom. Themes originating from the content analysis of the transcriptions were organised around four possible menu labelling formats: 1) numerical information on calories; 2) numerical information on calories and nutrients; 3) traffic light system plus Guideline Daily Amounts; 4) food information with ingredients list plus highlighted symbols. Results In both countries, participants preferred the ingredients list plus symbols format, considered more comprehensive and useful to make an informed food choice. Organic food and vegetarian symbols were the ones considered most important to appear on restaurant menu labels with ingredients list. However, most participants in Brazil and in the United Kingdom rejected the information restricted to calories and calories plus nutrients formats, saying that these would not influence their own choices. Conclusion This is the first multicultural qualitative study exploring preferences of people living in different countries with different eating habits, but where menu labelling is voluntary. Results evidenced similarities in participants' likes and dislikes for menu labelling formats in these two different contexts. Discussions showed participants in both countries prefer qualitative information than numerical information, suggesting that ingredients list and symbols provide information that people want to see on the menu

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Conservation Patterns of HIV-1 RT Connection and RNase H Domains: Identification of New Mutations in NRTI-Treated Patients

Background: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naıve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher’s exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions

A Novel Multiplex Cell Viability Assay for High-Throughput RNAi Screening

Cell-based high-throughput RNAi screening has become a powerful research tool in addressing a variety of biological questions. In RNAi screening, one of the most commonly applied assay system is measuring the fitness of cells that is usually quantified using fluorescence, luminescence and absorption-based readouts. These methods, typically implemented and scaled to large-scale screening format, however often only yield limited information on the cell fitness phenotype due to evaluation of a single and indirect physiological indicator. To address this problem, we have established a cell fitness multiplexing assay which combines a biochemical approach and two fluorescence-based assaying methods. We applied this assay in a large-scale RNAi screening experiment with siRNA pools targeting the human kinome in different modified HEK293 cell lines. Subsequent analysis of ranked fitness phenotypes assessed by the different assaying methods revealed average phenotype intersections of 50.7±2.3%–58.7±14.4% when two indicators were combined and 40–48% when a third indicator was taken into account. From these observations we conclude that combination of multiple fitness measures may decrease false-positive rates and increases confidence for hit selection. Our robust experimental and analytical method improves the classical approach in terms of time, data comprehensiveness and cost