Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

Background: Family studies support a genetic predisposition to inflammatory bowel diseases (IBD), but known genetic variants only partially explain the disease heritability. Families with multiple affected individuals potentially harbour rare and high-impact causal variants. Long regions of homozygosity due to recent inbreeding may increase the risk of individuals bearing homozygous loss-of-function variants. This study aimed to identify rare and homozygous genetic variants contributing to IBD. Methods: Four families with known consanguinity and multiple cases of IBD were recruited. In a family-specific analysis, we utilised homozygosity mapping complemented by whole-exome sequencing. Results: We detected a single region of homozygosity shared by Crohn's disease cases from a family of Druze ancestry, spanning 2.6 Mb containing the NOD2 gene. Whole-exome sequencing did not identify any potentially damaging variants within the region, suggesting that non-coding variation may be involved. In addition, affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1, WHAMM, DENND3, and C5. Conclusion: This study examined the potential contribution of rare, high-impact homozygous variants in consanguineous families with IBD. While the analysis was not designed to achieve statistical significance, our findings highlight genes or loci that warrant further research. Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn's disease

Fixed-Parameter Algorithms in Analysis of Heuristics for Extracting Networks in Linear Programs

We consider the problem of extracting a maximum-size reflected network in a linear program. This problem has been studied before and a state-of-the-art SGA heuristic with two variations have been proposed. In this paper we apply a new approach to evaluate the quality of SGA\@. In particular, we solve majority of the instances in the testbed to optimality using a new fixed-parameter algorithm, i.e., an algorithm whose runtime is polynomial in the input size but exponential in terms of an additional parameter associated with the given problem. This analysis allows us to conclude that the the existing SGA heuristic, in fact, produces solutions of a very high quality and often reaches the optimal objective values. However, SGA contain two components which leave some space for improvement: building of a spanning tree and searching for an independent set in a graph. In the hope of obtaining even better heuristic, we tried to replace both of these components with some equivalent algorithms. We tried to use a fixed-parameter algorithm instead of a greedy one for searching of an independent set. But even the exact solution of this subproblem improved the whole heuristic insignificantly. Hence, the crucial part of SGA is building of a spanning tree. We tried three different algorithms, and it appears that the Depth-First search is clearly superior to the other ones in building of the spanning tree for SGA. Thereby, by application of fixed-parameter algorithms, we managed to check that the existing SGA heuristic is of a high quality and selected the component which required an improvement. This allowed us to intensify the research in a proper direction which yielded a superior variation of SGA

Deep Graph Matching via Blackbox Differentiation of Combinatorial Solvers

Building on recent progress at the intersection of combinatorial optimization and deep learning, we propose an end-to-end trainable architecture for deep graph matching that contains unmodified combinatorial solvers. Using the presence of heavily optimized combinatorial solvers together with some improvements in architecture design, we advance state-of-the-art on deep graph matching benchmarks for keypoint correspondence. In addition, we highlight the conceptual advantages of incorporating solvers into deep learning architectures, such as the possibility of post-processing with a strong multi-graph matching solver or the indifference to changes in the training setting. Finally, we propose two new challenging experimental setups. The code is available at https://github.com/martius-lab/blackbox-deep-graph-matchingComment: ECCV 2020 conference pape

Seatbelt use and risk of major injuries sustained by vehicle occupants during motor-vehicle crashes: A systematic review and meta-analysis of cohort studies

BackgroundIn 2004, a World Health Report on road safety called for enforcement of measures such as seatbelt use, effective at minimizing morbidity and mortality caused by road traffic accidents. However, injuries caused by seatbelt use have also been described. Over a decade after publication of the World Health Report on road safety, this study sought to investigate the relationship between seatbelt use and major injuries in belted compared to unbelted passengers.MethodsCohort studies published in English language from 2005 to 2018 were retrieved from seven databases. Critical appraisal of studies was carried out using the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Pooled risk of major injuries was assessed using the random effects meta-analytic model. Heterogeneity was quantified using I-squared and Tau-squared statistics. Funnel plots and Egger's test were used to investigate publication bias. This review is registered in PROSPERO (CRD42015020309).ResultsEleven studies, all carried out in developed countries were included. Overall, the risk of any major injury was significantly lower in belted passengers compared to unbelted passengers (RR 0.47; 95%CI, 0.29 to 0.80; I-2=99.7; P=0.000). When analysed by crash types, belt use significantly reduced the risk of any injury (RR 0.35; 95%CI, 0.24 to 0.52). Seatbelt use reduces the risk of facial injuries (RR=0.56, 95% CI=0.37 to 0.84), abdominal injuries (RR=0.87; 95% CI=0.78 to 0.98) and, spinal injuries (RR=0.56, 95% CI=0.37 to 0.84). However, we found no statistically significant difference in risk of head injuries (RR=0.49; 95% CI=0.22 to 1.08), neck injuries (RR=0.69: 95%CI 0.07 to 6.44), thoracic injuries (RR 0.96, 95%CI, 0.74 to 1.24), upper limb injuries (RR=1.05, 95%CI 0.83 to 1.34) and lower limb injuries (RR=0.77, 95%CI 0.58 to 1.04) between belted and non-belted passengers.ConclusionIn sum, the risk of most major road traffic injuries is lower in seatbelt users. Findings were inconclusive regarding seatbelt use and susceptibility to thoracic, head and neck injuries during road traffic accidents. Awareness should be raised about the dangers of inadequate seatbelt use. Future research should aim to assess the effects of seatbelt use on major injuries by crash type

Detecting a stochastic gravitational wave background with the Laser Interferometer Space Antenna

The random superposition of many weak sources will produce a stochastic background of gravitational waves that may dominate the response of the LISA (Laser Interferometer Space Antenna) gravitational wave observatory. Unless something can be done to distinguish between a stochastic background and detector noise, the two will combine to form an effective noise floor for the detector. Two methods have been proposed to solve this problem. The first is to cross-correlate the output of two independent interferometers. The second is an ingenious scheme for monitoring the instrument noise by operating LISA as a Sagnac interferometer. Here we derive the optimal orbital alignment for cross-correlating a pair of LISA detectors, and provide the first analytic derivation of the Sagnac sensitivity curve.Comment: 9 pages, 11 figures. Significant changes to the noise estimate

In ricordo di Paolo Sylos Labini

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Exploring the views of young women and their healthcare professionals on dietary habits and supplementation practices in adolescent pregnancy: a qualitative study

Background: Nutrition is a modifiable factor affecting foetal growth and pregnancy outcomes. Inadequate nutrition is of particular concern in adolescent pregnancies with poor quality diet and competing demands for nutrients. The aim of this study was to explore knowledge and understanding of nutrition advice during adolescent pregnancy,and identify barriers and facilitators to dietary change and supplementation use in this vulnerable population. Methods: Semi-structured interviews were conducted with young women and key antenatal healthcare providers: midwives, family nurses and obstetricians. Doncaster, Manchester and London were chosen as sites offering different models of midwifery care alongside referral to the Family Nurse Partnership programme. Results: A total of 34 young women (adolescents aged 16–19 years) and 20 health professionals were interviewed. Young women made small changes to their dietary intake despite limited knowledge and social constraints. Supplementation use varied; the tablet format was identified by few participants as a barrier but forgetting to take them was the main reason for poor adherence. Health professionals provided nutrition information but often lack the time and resources to tailor this appropriately. Young women’s prime motivator was a desire to have a healthy baby; they wanted to understand the benefits of supplementation and dietary change in those terms. Conclusion: Pregnancy is a window of opportunity for improving nutrition but often constrained by social circumstances. Health professionals should be supported in their role to access education, training and resources which build their self-efficacy to facilitate change in this vulnerable population group beyond the routine care they provide

Calibration and Characterization of the IceCube Photomultiplier Tube

Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure

All-particle cosmic ray energy spectrum measured with 26 IceTop stations

We report on a measurement of the cosmic ray energy spectrum with the IceTop air shower array, the surface component of the IceCube Neutrino Observatory at the South Pole. The data used in this analysis were taken between June and October, 2007, with 26 surface stations operational at that time, corresponding to about one third of the final array. The fiducial area used in this analysis was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV measured for three different zenith angle ranges between 0{\deg} and 46{\deg}. Because of the isotropy of cosmic rays in this energy range the spectra from all zenith angle intervals have to agree. The cosmic-ray energy spectrum was determined under different assumptions on the primary mass composition. Good agreement of spectra in the three zenith angle ranges was found for the assumption of pure proton and a simple two-component model. For zenith angles {\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on composition assumption. Spectral indices above the knee range from -3.08 to -3.11 depending on primary mass composition assumption. Moreover, an indication of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure