486 research outputs found

    Factors that comprise driver boredom and their relationships to preferred driving speed and demographic variables.

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    Driver boredom is an area of driver behaviour that has received limited attention. This study explores the factor structure underlying driver boredom and investigates age and gender differences in the experience of driver boredom and preferred driving speeds using a self-report questionnaire. A rotated principle components analysis of 49 attitude items yielded four dimensions: responses to under-stimulation, flow, lapse and error proneness and anxiety. Age and gender differences were found in these dimensions as well as in preferred driving speeds; two of the factors, responses to under-stimulation and flow were particularly related to preferred driving speeds on all but urban roads. These findings are considered in terms of cognitive capacity required for driving, self-reporting of cognitive failure and error-proneness and the implications for drivers maintaining safety margins when bored

    De novo SCN1A mutations in Dravet syndrome and related epileptic encephalopathies are largely of paternal origin

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    Background: Dravet syndrome is a severe infantile epileptic encephalopathy caused in approximately 80% of cases by mutations in the voltage gated sodium channel subunit gene SCN1A. The majority of these mutations are de novo. The parental origin of de novo mutations varies widely among genetic disorders and the aim of this study was to determine this for Dravet syndrome. Methods: 91 patients with de novo SCN1A mutations and their parents were genotyped for single nucleotide polymorphisms (SNPs) in the region surrounding their mutation. Allele specific polymerase chain reaction (PCR) based on informative SNPs was used to separately amplify and sequence the paternal and maternal alleles to determine in which parental chromosome the mutation arose. Results: The parental origin of SCN1A mutations was established in 44 patients for whom both parents were available and SNPs were informative. The mutations were of paternal origin in 33 cases and of maternal origin in the remaining 11 cases. De novo mutation of SCN1A most commonly, but not exclusively, originates from the paternal chromosome. The average age of parents originating mutations did not differ from that of the general population. Conclusions: The greater frequency of paternally derived mutations in SCN1A is likely to be due to the greater chance of mutational events during the increased number of mitoses which occur during spermatogenesis compared to oogenesis, and the greater susceptibility to mutagenesis of the methylated DNA characteristic of sperm cells.Sarah E. Heron, Ingrid E. Scheffer, Xenia Iona, Sameer M. Zuberi, Rachael Birch, Jacinta M. McMahon, Carla M. Bruce, Samuel F. Berkovic, John C. Mulle

    Transcript abundance of photorhabdus insect-related (Pir) toxin in Manduca sexta and Galleria mellonella infections

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    In this study, we assessed pirAB toxin transcription in Photorhabdus luminescens laumondii (strain TT01) (Enterobacteriaceae) by comparing mRNA abundance under in vivo and in vitro conditions. In vivo assays considered both natural and forced infections with two lepidopteran hosts: Galleria mellonella and Manduca sexta. Three portals of entry were utilized for the forced infection assays: (a) integument; (b) the digestive route (via mouth and anus); and (c) the tracheal route (via spiracles). We also assessed plu4093-2 transcription during the course of a natural infection; this is when the bacteria are delivered by Heterorhabditis bacteriophora nematodes. Transcript abundance in G. mellonella was higher than in M. sexta at two of the observed time points: 15 and 18 h. Expression of pirAB plu4093-2 reached above endogenous control levels at 22 h in G. mellonella but not in M. sexta. Overall, pirAB plu4093-2 transcripts were not as highly expressed in M. sexta as in G. mellonella, from 15 to 22 h. This is the first study to directly compare pirAB plu4093-2 toxin transcript production considering different portals of entry

    The role of seizure-related SEZ6 as a susceptibility gene in febrile seizures

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    Sixty cases of febrile seizures from a Chinese cohort had previously been reported with a strong association between variants in the seizure-related (SEZ) 6 gene and febrile seizures. They found a striking lack of genetic variation in their controls. We found genetic variation in SEZ6 at similar levels at the same DNA sequence positions in our 94 febrile seizure cases as in our 96 unaffected controls. Two of our febrile seizure cases carried rare variants predicted to have damaging consequences. Combined with some of the variants from the Chinese cohort, these data are compatible with a role for SEZ6 as a susceptibility gene for febrile seizures. However, the polygenic determinants underlying most cases of febrile seizures with complex inheritance remain to be determined.John C. Mulley, Xenia Iona, Bree Hodgson, Sarah E. Heron, Samuel F. Berkovic, Ingrid E. Scheffer and Leanne M. Dibben

    A new chromosome-assigned Mongolian gerbil genome allows characterization of complete centromeres and a fully heterochromatic chromosome

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    This is the final version. Available on open access from Oxford University Press via the DOI in this recordData Availability: All sequencing data and the genome are available under SRA BioProject PRJNA397533. Specific accession numbers can be found in supplementary material S1, Supplementary Material online. This Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the accession JAODIK000000000. The version described in this paper is version JAODIK010000000. The genetic map, a vcf of the genetic markers and their genotypes in the mapping panel, the gff of the gene annotations, the gff of the repetitive element annotations, and “Supplemental_Material 3_codebase.zip”, can be found in the Dryad repository here: Brekke, Thomas D. (2022), Data for “The origin of a new chromosome in gerbils”, Dryad, Dataset, https://doi.org/10.5061/dryad.1vhhmgqws.Chromosome-scale genome assemblies based on ultralong-read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus), which includes the complete sequence of all centromeres. Gerbils are thus the one of the first vertebrates to have their centromeres completely sequenced. Gerbil centromeres are composed of four different repeats of length 6, 37, 127, or 1,747 bp, which occur in simple alternating arrays and span 1-6 Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intraarm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150 kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data and highlight novel patterns involved in the evolution of chromosomes.Leverhulme TrustNatural Environment Research Council (NERC)Ministerio de Economía y Competitivida

    Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

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    Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers
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