573 research outputs found
Eventâscale dynamics of a parabolic dune and its relevance for mesoscale evolution
Parabolic dunes are wide-spread aeolian landforms found in a variety of environments. Despite modelling advances and good understanding of how they evolve, there is limited empirical data on their dynamics at short time-scales of hours, and on how these dynamics relate to their medium-term evolution. This study presents the most comprehensive dataset to date on aeolian processes (airflow and sediment transport) inside a parabolic dune at an event-scale. This is coupled with information on elevation changes inside the landform to understand its morphological response to a single wind event. Results are contextualized against the medium-term (years) allowing us to investigate one of the most persistent conundrums in geomorphology, that of the significance of short-term findings for landform evolution. Our field data suggested three key findings: 1) sediment transport rates inside parabolic dunes correlate well with wind speeds rather than turbulence; 2) up to several tonnes of sand can move through these landforms in a few hours; 3) short-term elevation changes inside parabolic dunes can be complex and different from long-term net spatial patterns, including simultaneous erosion and accumulation along the same wall. Modeled airflow patterns along the basin were similar to those measured in situ for a range of common wind directions, demonstrating the potential for strong transport during multiple events. Meso-scale analyses suggested that the measured event was representative of the type of events potentially driving significant geomorphic changes over years, with supply-limiting conditions playing an important role in resultant flux amounts
Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice
Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway
Medical applicant general practice experience and career aspirations: a questionnaire study
Background: Increasing access to general practice work experience placements for school students
is a strategy for improving general practice recruitment, despite limited evidence and concerns
surrounding equity of access to general practice experiences.
Aims: To examine the association between undertaking general practice experience and the
perceptions of general practice as an appealing future career among prospective medical applicants.
To identify socioeconomic factors associated with obtaining general practice experience.
Design & setting: Cross-sectional questionnaire study in the UK.
Method: Participants were UK residents aged â„16 years and seriously considering applying to study
medicine in 2019/2020. They were invited to take part via the University Clinical Aptitude Test (UCAT).
Questionnaire data were analysed using a linear regression of general practice appeal on general
practice experience, adjusting for career motivations and demographics, and a logistic regression of
general practice experience on measures of social capital and demographics.
Results: Of 6391 responders, 4031 were in their last year of school. General practice experience
predicted general practice appeal after adjusting for career motivation and demographics (b = 0.37,
standard error [SE] = 0.06, P<0.00001). General practice experience was more common among
students at private (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.31 to 2.08, P<0.0001) or
grammar schools (OR = 1.33, 95% CI = 1.02 to 1.72, P = 0.03) and in the highest socioeconomic group
(OR = 1.62, 95% CI = 1.28 to 2.05, P<0.0001), and less likely among students of âotherâ ethnicity (OR
= 0.37, 95% CI = 0.20 to 0.67, P = 0.0011).
Conclusion: Having general practice experience prior to medical school was associated with finding
general practice appealing, which supports its utility in recruitment. Applicants from more deprived
backgrounds were less likely to have had a general practice experience, possibly through lack of
accessible opportunities
Subjective evaluation of the environmental quality in China's industrial corridors.
Based on 270 questionnaire surveys in 8 cities of 5 industrial corridors in China, this study
aims to examine the effects of industry construction on the evaluation of environmental pollution, natural
environment, built environment, personal perception and development and policy. The results show that
the evaluations on environmental pollution and landscape design are both below the medium level, but
the evaluations of the living comfort and safety are both above the medium level. Further analysis,
females usually give lower evaluation scores than males, and age and health situations are negatively
related to the evaluation results; People indicate a great desire to reduce the environmental pollution and
protect the natural environment. Moreover, the landscape was analysed using colour extraction
techniques based on video recording, there are significant correlations between industrial pixel ratio and
evaluation results of air quality, vegetation pixel ratio and evaluation results of river water quality, and
public facilities pixel ratio and evaluation results of comfort levels
Vascular effects of apelin in vivo in man
ObjectivesThis study was designed to establish the direct vascular effects of apelin in vivo in man.BackgroundApelin is the endogenous ligand for the previously orphaned G-proteinâcoupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation.MethodsVascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr1)apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr1)apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a ânitric oxide clampâ (nitric oxide synthase inhibitor, L-NG-monomethylarginine [8 ÎŒmol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo.ResultsAlthough sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr1)apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr1)apelin-13âmediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7).ConclusionsAlthough having no apparent effect on venous tone, apelin causes nitric oxideâdependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis
Bullet impacts and built heritage damage 1640â1939
© 2018, The Author(s). Conflict damage to heritage has been thrust into the global spotlight during recent conflict in the Middle East. While the use of social media has heightened and enhanced public awareness of this âcultural terrorismâ, the occurrence of this type of vandalism is not new. In fact, as this study demonstrates, evidence of the active targeting of sites, as well as collateral damage when heritage is caught in crossfire, is widely visible around Europe and further afield. Using a variety of case studies ranging from the 1640s to the 1930s, we illustrate and quantify the changing impact of ballistics on heritage buildings as weaponry and ammunition have increased in both energy and energy density potential. In the first instance, this study highlights the increasing threats to heritage in conflict areas. Second, it argues for the pressing need to quantify and map damage to the stonework in order to respond to these challenges
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Anticipatory governance for social-ecological resilience
Anticipation is increasingly central to urgent contemporary debates, from climate change to the global economic crisis. Anticipatory practices are coming to the forefront of political, organizational, and citizensâ society. Research into anticipation, however, has not kept pace with public demand for insights into anticipatory practices, their risks and uses. Where research exists, it is deeply fragmented. This paper seeks to identify how anticipation is defined and understood in the literature and to explore the role of anticipatory practice to address individual, social, and global challenges. We use a resilience lens to examine these questions. We illustrate how varying forms of anticipatory governance are enhanced by multi-scale regional networks and technologies and by the agency of individuals, drawing from an empirical case study on regional water governance of Malaren, Sweden. Finally, we discuss how an anticipatory approach can inform adaptive institutions, decision making, strategy formation, and societal resilience
Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.
BACKGROUND: Germline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype-phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers. METHODS: A retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses. RESULTS: Tumour risks analysis provided novel penetrance estimates and genotype-phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%). CONCLUSIONS: Overall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers
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