Intracanopy adjustment of leaf-level thermal tolerance is associated with microclimatic variation across the canopy of a desert tree (Acacia papyrocarpa)

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Tree crowns are spatially heterogeneous, sometimes resulting in significant variation in microclimate across the canopy, particularly with respect to temperature. Yet it is not known whether such localised temperature variation equates to intracanopy variation in leaf-level physiological thermal tolerance. Here, we studied whether microclimate variation across the canopy of a dominant desert tree equated to localised variation in leaf thermal thresholds (T 50 ) among four canopy positions: upper south, upper north, lower south, lower north. Principal component analysis was used to generate a composite climatic stress variable (C STRESS ) from canopy temperature, vapour pressure deficit, and relative humidity. We also determined the average number of days that maximum temperatures exceeded the air temperature equating to this species’ critical threshold of 49 °C (AT 49 ). To estimate how closely leaf temperatures track ambient temperature, we predicted the thermal time constant (τ) for leaves at each canopy position. We found that C STRESS and AT 49 were significantly greater in lower and north-facing positions in the canopy. Differences in wind speed with height resulted in significantly longer predicted τ for leaves positioned at lower, north-facing positions. Variation in these drivers was correlated with significantly higher T 50 for leaves in these more environmentally stressful canopy positions. Our findings suggest that this species may optimise resources to protect against thermal damage at a whole-plant level. They also indicate that, particularly in desert environments with steep intracanopy microclimatic gradients, whole-plant carbon models could substantially under- or overestimate productivity under heat stress, depending on where in the canopy T 50 is measured

Lithium chloride modulates chondrocyte primary cilia and inhibits Hedgehog signaling

This work was supported in part by funding from the AO Foundation (project S-12-15K) and the Medical Research Council (Swindon, United Kingdom) (MR/L002876/1). C.A.P. was supported by the Royal Society of New Zealand through a James Cook Research Fellowshi

Feasibility of cardiopulmonary exercise testing in idiopathic pulmonary fibrosis

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordBritish Thoracic Society Winter Meeting 2018, London, UK, 5-7 December 2018Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of irreversible declining lung function. Reductions in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) are the common clinical endpoints for prognostic monitoring and assessing treatment outcomes. The use of cardiopulmonary exercise testing (CPET) in IPF remains largely unexplored. Objectives To explore the feasibility of CPET as a clinical measure in IPF and identify associations with established clinical variables. Methods Seventeen patients with IPF were approached, and fifteen (88%) were recruited (13 male, 68.1±7.5 years). Incremental exercise testing to exhaustion was undertaken via electronically braked cycle ergometer. Variables included: peak oxygen consumption (VO2peak), peak work rate (WRpeak), nadir SpO2, ventilatory drive (VE/VCO2), alongside standard clinical pulmonary function tests of FVC and DLCO. Pearson’s correlation coefficients established relationships between variables. Results One participant was excluded (high baseline systolic blood pressure). Eight out of fourteen (57%) participants reached volitional exhaustion. Five CPETs were terminated early due to desaturation (SpO2 <88%) and one to an exercise-induced right bundle branch block (recovery within minutes of ceasing exercise). Mean (±SD) pulmonary and exercise results were: FVC, 84.9%±17.0%; DLCO, 56.5%±11.4%; VO2peak, 1.4±0.4 L.min-1, 16.5±5.5 mL.kg-1.min-1; WRpeak, 104±42 W; SpO2, 90±3%; VE/VCO2, 27.1±6.4. Significant correlations were identified between: FVC and SpO2 (r=0.58, p=0.032), DLCO and VE/VCO2 (r=0.81, p<0.001) and WRpeak (r=0.58, p=0.03). Body-mass relative VO2peak held moderate, but not significant relationships with FVC (r=0.44, p=0.11) and DLCO (r=0.53, p=0.51). Conclusions Initial findings from this study have found CPET to be acceptable to patients with IPF and potentially feasible as a testing measure. Preliminary results identified common exercise desaturation, suggesting less conservative SpO2 termination criteria (e.g. 80% cut-off) could be considered. Although exercise parameters held limited relationships with FVC and DLCO, results from VO2peak identifies potential additional and dynamic prognostic information and warrants further investigation.Royal Devon & Exeter Hospita

The value of best-practice guidelines for OSCEs in a postgraduate program in an Australian remote area setting

© CA Jeffery, ML Mitchell, A Henderson, S Lenthall, S Knight, P Glover, M Kelly, D Nulty, M Groves, 2014. Introduction: Nurses in remote areas of Australia are the primary healthcare professionals, who need to be able to deliver comprehensive and culturally sensitive care to clients, many of whom are Indigenous Australians. Adequate and specific preparation for practice is crucial to the quality of care delivered by remote area nurses (RANs). Objective structured clinical examinations (OSCE) provide an excellent opportunity for student practice in a simulated environment that is safe, authentic, fair and valid when well constructed. Seven integrated best practice guidelines (BPGs), previously developed by project team members to inform OSCEs within educational programs, provided guidance in restructuring the OSCE. This paper provides a detailed analysis of the value of BPGs used in the development, teaching and learning, and evaluation of OSCEs in a rural and remote postgraduate course for RANs. Method: A pre-site visit to the Centre for Remote Health, Alice Springs, Northern Territory, was conducted with modification of the course and previous OSCE according to BPGs. Following delivery of the course and OSCE, evaluations occurred via a mixed method approach. Student surveys (n=15) and focus groups (n=13) and staff interviews (n=5) provided an in-depth analysis of their perceptions of the revised OSCE. Descriptive statistics were used to describe the student sample. The narrative data were transcribed verbatim and analysed using content analysis. Triangulation was achieved with the convergence of the separate data sources focusing on themes and patterns within and between students and tutors. Results: All 15 students and five tutors provided feedback. The majority of student participants had limited experience in working in remote area nursing prior to participation and therefore the opportunities that availed themselves were critical in adequately equipping them with the requisite knowledge, skills and abilities. Three themes emerged from the data: (1) value of common and significant events in OSCE; (2) power of deliberate actions; and (3) learning cultural sensitivity. Discussion: OSCEs in this setting proved to be a good way for students to learn the skills required by RANs. Overwhelmingly, the modifications using the BPGs were highly valued by students and staff. Three themes emerged and were clearly linked to specific BPGs, indicating the positive impact the BPGs had on the OSCEs and student learning. The authentic content for the scenarios was seen as relevant and motivational for student learning. The practice element of the OSCEs enhanced the learning experience and feedback supported learning. Conclusions: OSCEs developed, taught and assessed using BPGs were highly valued. The BPGs provided an integrated approach with real-life scenarios with a strong cultural perspective - all important features to the RANs' future success in providing individualised care to clients in remote areas of Australia. Further use of BPGs is recommended

Cardiopulmonary Exercise Testing as a Longitudinal Clinical Tool in Interstitial Lung Disease Management

This is an abstract from International Conference of the American-Thoracic-Society Location: Dallas, TX Date: MAY 17-22, 2019Royal Devon & Exeter Hospita

Monotonicity of Fitness Landscapes and Mutation Rate Control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Young men’s views towards the barriers and facilitators of internet-based Chlamydia trachomatis screening: a qualitative study

Background: There is a growing number of Internet-based approaches that offer young people screening for sexually transmitted infections. Objective: This paper explores young men’s views towards the barriers and facilitators of implementing an Internet-based screening approach. The study sought to consider ways in which the proposed intervention would reach and engage men across ages and socioeconomic backgrounds. Methods: This qualitative study included 15 focus groups with 60 heterosexual young men (aged 16-24 years) across central Scotland, drawn across age and socioeconomic backgrounds. Focus groups began by obtaining postcode data to allocate participants to a high/low deprivation category. Focus group discussions involved exploration of men’s knowledge of chlamydia, use of technology, and views toward Internet-based screening. Men were shown sample screening invitation letters, test kits, and existing screening websites to facilitate discussions. Transcripts from audio recordings were analyzed with "Framework Analysis". Results: Men’s Internet and technology use was heterogeneous in terms of individual practices, with greater use among older men (aged 20-24 years) than teenagers and some deprivation-related differences in use. We detail three themes related to barriers to successful implementation: acceptability, confidentiality and privacy concerns, and language, style, and content. These themes identify ways Internet-based screening approaches may fail to engage some men, such as by raising anxiety and failing to convey confidentiality. Men wanted screening websites to frame screening as a serious issue, rather than using humorous images and text. Participants were encouraged to reach a consensus within their groups on their broad design and style preferences for a screening website; this led to a set of common preferences that they believed were likely to engage men across age and deprivation groups and lead to greater screening uptake. Conclusions: The Internet provides opportunities for re-evaluating how we deliver sexual health promotion and engage young men in screening. Interventions using such technology should focus on uptake by age and socioeconomic background. Young people should be engaged as coproducers of intervention materials and websites to ensure messages and content are framed appropriately within a fast-changing environment. Doing so may go some way to addressing the overall lower levels of testing and screening among men compared with women

Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet

Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD