207 research outputs found

    The Social context of motorcycle riding and the key determinants influencing rider behavior: A qualitative investigation

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    Objective: Given the increasing popularity of motorcycle riding and heightened risk of injury or death associated with being a rider, this study explored rider behaviour as a determinant of rider safety and, in particular, key beliefs and motivations which influence such behaviour. To enhance the effectiveness of future education and training interventions, it is important to understand riders’ own views about what influences how they ride. Specifically, this study sought to identify key determinants of riders’ behaviour in relation to the social context of riding including social and identity-related influences relating to the group (group norms and group identity) as well as the self (moral/personal norm and self-identity). ----- ----- Method: Qualitative research was undertaken via group discussions with motorcycle riders (n = 41). Results: The findings revealed that those in the group with which one rides represent an important source of social influence. Also, the motorcyclist (group) identity was associated with a range of beliefs, expectations, and behaviours considered to be normative. Exploration of the construct of personal norm revealed that riders were most cognizant of the β€œwrong things to do” when riding; among those issues raised was the importance of protective clothing (albeit for the protection of others and, in particular, pillion passengers). Finally, self-identity as a motorcyclist appeared to be important to a rider’s self-concept and was likely to influence their on-road behaviour. ----- ----- Conclusion: Overall, the insight provided by the current study may facilitate the development of interventions including rider training as well as public education and mass media messages. The findings suggest that these interventions should incorporate factors associated with the social nature of riding in order to best align it with some of the key beliefs and motivations underpinning riders’ on-road behaviours

    In-hospital extracorporeal cardiopulmonary resuscitation for patients with an out-of-hospital cardiac arrest in a semi-rural setting:An observational study on the implementation of a helicopter emergency medical services pathway

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    AIM: In this study, we aimed to investigate the efficacy of a helicopter emergency medical service (HEMS) facilitated pathway for in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) for patients with an out of hospital cardiac arrest (OHCA) in a semi-rural setting. METHODS: We retrospectively reviewed all patients with an OHCA attended by a UK HEMS service between 1 January 2018 and 20 September 2021, when a dedicated ECPR pathway was in effect to facilitate transport of eligible patients to the nearest ECLS centre. The primary endpoint was the number of patients meeting ECPR eligibility criteria at three pre-defined time points: at HEMS dispatch, during on-scene evaluation and upon arrival in hospital. RESULTS: During the study period, 162 patients attended met ECPR pathway dispatch criteria. After on-scene evaluation, 74 patients (45%) had a return of spontaneously circulation before arrival of HEMS, 60 (37%) did not meet eligibility criteria regarding initial rhythm or etiology of the OHCA, and 15 (9%) had deteriorated (mainly into asystole) and were no longer suitable candidates upon arrival of HEMS. Eleven patients were eligible for ECPR and transported to hospital in arrest, and a further two patients were transported for post-ROSC ECLS. Nine patients deteriorated during transport and were no longer suitable ECPR candidates upon arrival. ECLS was successfully initiated in two patients (one intra-arrest, and one post-ROSC). CONCLUSION: In-hospital ECPR is of limited value for patients with refractory OHCA in a semi-rural setting, even when a dedicated pathway is in place. Potentially eligible patients often cannot be transported within an appropriate timeframe and/or deteriorate before arrival in hospital

    The fate of the homoctenids (Tentaculitoidea) during the Frasnian-Famennian mass extinction (Late Devonian)

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    The homoctenids (Tentaculitoidea) are small, conical-shelled marine animals which are amongst the most abundant and widespread of all Late Devonian fossils. They were a principal casualty of the Frasnian-Famennian (F-F, Late Devonian) mass extinction, and thus provide an insight into the extinction dynamics. Despite their abundance during the Late Devonian, they have been largely neglected by extinction studies. A number of Frasnian-Famennian boundary sections have been studied, in Poland, Germany, France, and the United States. These sections have yielded homoctenids, which allow precise recognition of the timing of the mass extinction. It is clear that the homoctenids almost disappear from the fossil record during the latest Frasnian β€œUpper Kellwasser Event”. The coincident extinction of this pelagic group, and the widespread development of intense marine anoxia within the water column, provides a causal link between anoxia and the F-F extinction. Most notable is the sudden demise of a group, which had been present in rock-forming densities, during this anoxic event. One new species, belonging to Homoctenus is described, but is not formally named here

    Moisture susceptibility of high and low compaction dry process crumb rubber modified asphalt mixtures

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    The field performance of dry process crumb rubber-modified (CRM) asphalt mixtures has been reported to be inconsistent with stripping and premature cracking on the surfacing. One of the concerns is that, because achieving field compaction of CRM material is difficult due to the inherent resilient nature of the rubber particle, nonuniform field compaction may lead to a deficient bond between rubber and bitumen. To assess the influence of compaction, a series of CRM and control mixtures was produced and compacted at two levels: 4% (low, optimum laboratory compaction) and 8% (high, field experience) air void content. The long-term durability, in regard to moisture susceptibility of the mixtures, was assessed by conducting repeated moisture conditioning cycles. Mechanical properties (stiffness, fatigue, and resistance to permanent deformation) were determined in the Nottingham Asphalt Tester. Results indicated that compared with conventional mixtures, the CRM mixtures, regardless of compaction effort, are more susceptible to moisture with the degree of susceptibility primarily depending on the amount of rubber in the mixture, rather than the difference in compaction. This behavior is different from that of conventional mixtures in which, as expected, poorly compacted mixtures were found to be more susceptible to moisture than were well-compacted mixtures

    Prospective observational study to examine health-related quality of life and develop models to predict long-term patient-reported outcomes 6 months after hospital discharge with blunt thoracic injuries.

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    OBJECTIVE: This study aimed to examine the long-term outcomes and health-related quality of life in patients with blunt thoracic injuries over 6 months from hospital discharge and develop models to predict long-term patient-reported outcomes. DESIGN: A prospective observational study using longitudinal survey design. SETTING: The study recruitment was undertaken at 12 UK hospitals which represented diverse geographical locations and covered urban, suburban and rural areas across England and Wales. PARTICIPANTS: 337 patients admitted to hospital with blunt thoracic injuries were recruited between June 2018-October 2020. METHODS: Participants completed a bank of two quality of life surveys (Short Form-12 (SF-12) and EuroQol 5-Dimensions 5-Levels) and two pain questionnaires (Brief Pain Inventory and painDETECT Questionnaire) at four time points over the first 6 months after discharge from hospital. A total of 211 (63%) participants completed the outcomes data at 6 months after hospital discharge. OUTCOMES MEASURES: Three outcomes were measured using pre-existing and validated patient-reported outcome measures. Outcomes included: Poor physical function (SF-12 Physical Component Score); chronic pain (Brief Pain Inventory Pain Severity Score); and neuropathic pain (painDETECT Questionnaire). RESULTS: Despite a trend towards improving physical functional and pain at 6 months, outcomes did not return to participants perceived baseline level of function. At 6 months after hospital discharge, 37% (n=77) of participants reported poor physical function; 36.5% (n=77) reported a chronic pain state; and 22% (n=47) reported pain with a neuropathic component. Predictive models were developed for each outcome highlighting important data collection requirements for predicting long-term outcomes in this population. Model diagnostics including calibration and discrimination statistics suggested good model fit in this development cohort. CONCLUSIONS: This study identified the recovery trajectories for patients with blunt thoracic injuries over the first 6 months after hospital discharge and present prognostic models for three important outcomes which after external validation could be used as clinical risk stratification scores

    Quantitative trait locus analysis identifies Gabra3 as a regulator of behavioral despair in mice

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    The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (nΒ =Β 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identify potential candidate genes within the MMUX QTLs identified in the NZB/BlNJΒ Γ—Β RIIIS/J cross. Expression of Gabra3, which encodes the GABAA receptor Ξ±3 subunit, was robust in the hippocampus of B6 and RIIIS mice but absent from NZB hippocampal tissue. To verify the role of Gabra3 in regulating TST behavior in vivo, mice were treated with SB-205384, a positive modulator of the Ξ±3 subunit. SB-205384 significantly reduced TST immobility in B6 mice without affecting general activity, but it had no effect on behavior in NZB mice. This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression

    MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

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    There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

    Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons

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    The inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their cortex and hippocampus. To ascertain consequences of these changes in the GABAergic system, we performed a battery of behavioral assays on the Dlx1 mutant mice, including zero maze, open field, locomotor activity, food intake, rotarod, tail suspension, fear conditioning assays (context and trace), prepulse inhibition, and working memory related tasks (spontaneous alteration task and spatial working memory task). Dlx1 mutant mice displayed elevated activity levels in open field, locomotor activity, and tail suspension tests. These mice also showed deficits in contextual and trace fear conditioning, and possibly in prepulse inhibition. Their learning deficits were not global, as the mutant mice did not differ from the wild-type controls in tests of working memory. Our findings demonstrate a critical role for the Dlx1 gene, and likely the subclasses of interneurons that are affected by the lack of this gene, in behavioral inhibition and associative fear learning. These observations support the involvement of particular components of the GABAergic system in specific behavioral phenotypes related to complex neuropsychiatric diseases

    Phenotypic Characterization of a Genetically Diverse Panel of Mice for Behavioral Despair and Anxiety

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    Animal models of human behavioral endophenotypes, such as the Tail Suspension Test (TST) and the Open Field assay (OF), have proven to be essential tools in revealing the genetics and mechanisms of psychiatric diseases. As in the human disorders they model, the measurements generated in these behavioral assays are significantly impacted by the genetic background of the animals tested. In order to better understand the strain-dependent phenotypic variability endemic to this type of work, and better inform future studies that rely on the data generated by these models, we phenotyped 33 inbred mouse strains for immobility in the TST, a mouse model of behavioral despair, and for activity in the OF, a model of general anxiety and locomotor activity.We identified significant strain-dependent differences in TST immobility, and in thigmotaxis and distance traveled in the OF. These results were replicable over multiple testing sessions and exhibited high heritability. We exploited the heritability of these behavioral traits by using in silico haplotype-based association mapping to identify candidate genes for regulating TST behavior. Two significant loci (-logp >7.0, gFWER adjusted p value <0.05) of approximately 300 kb each on MMU9 and MMU10 were identified. The MMU10 locus is syntenic to a major human depressive disorder QTL on human chromosome 12 and contains several genes that are expressed in brain regions associated with behavioral despair.We report the results of phenotyping a large panel of inbred mouse strains for depression and anxiety-associated behaviors. These results show significant, heritable strain-specific differences in behavior, and should prove to be a valuable resource for the behavioral and genetics communities. Additionally, we used haplotype mapping to identify several loci that may contain genes that regulate behavioral despair
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