Treatment threshold for intra-operative hypotension in clinical practice-a prospective cohort study in older patients in the UK

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure 20%; systolic blood pressure 20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension

Treatment threshold for intra‐operative hypotension in clinical practice—a prospective cohort study in older patients in the UK

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure 20%; systolic blood pressure 20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension

Induction and Maintenance of CX3CR1-Intermediate Peripheral Memory CD8(+) T Cells by Persistent Viruses and Vaccines

The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory. In humans, CX3CR1int CD8+ T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (HCV) (ChAd3-NSmut) and during natural CMV infection and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1int cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans

Ring distributions leading to species formation: a global topographic analysis of geographic barriers associated with ring species

<p>Abstract</p> <p>Background</p> <p>In the mid 20^thcentury, Ernst Mayr and Theodosius Dobzhansky championed the significance of circular overlaps or ring species as the perfect demonstration of speciation, yet in the over 50 years since, only a handful of such taxa are known. We developed a topographic model to evaluate whether the geographic barriers that favor processes leading to ring species are common or rare, and to predict where other candidate ring barriers might be found.</p> <p>Results</p> <p>Of the 952,147 geographic barriers identified on the planet, only about 1% are topographically similar to barriers associated with known ring taxa, with most of the likely candidates occurring in under-studied parts of the world (for example, marine environments, tropical latitudes). Predicted barriers separate into two distinct categories: (i) single cohesive barriers (< 50,000 km²), associated with taxa that differentiate at smaller spatial scales (salamander: <it>Ensatina eschscholtzii</it>; tree: <it>Acacia karroo</it>); and (ii) composite barriers - formed by groups of barriers (each 184,000 to 1.7 million km²) in close geographic proximity (totaling 1.9 to 2.3 million km²) - associated with taxa that differentiate at larger spatial scales (birds: <it>Phylloscopus trochiloide</it>s and <it>Larus </it>(sp. <it>argentatus </it>and <it>fuscus</it>)). When evaluated globally, we find a large number of cohesive barriers that are topographically similar to those associated with known ring taxa. Yet, compared to cohesive barriers, an order of magnitude fewer composite barriers are similar to those that favor ring divergence in species with higher dispersal.</p> <p>Conclusions</p> <p>While these findings confirm that the topographic conditions that favor evolutionary processes leading to ring speciation are, in fact, rare, they also suggest that many understudied natural systems could provide valuable demonstrations of continuous divergence towards the formation of new species. Distinct advantages of the model are that it (i) requires no <it>a priori </it>information on the relative importance of features that define barriers, (ii) can be replicated using any kind of continuously distributed environmental variable, and (iii) generates spatially explicit hypotheses of geographic species formation. The methods developed here - combined with study of the geographical ecology and genetics of taxa in their environments - should enable recognition of ring species phenomena throughout the world.</p

Asymmetric reproductive isolation between terminal forms of the salamander ring species Ensatina eschscholtzii revealed by fine-scale genetic analysis of a hybrid zone

<p>Abstract</p> <p>Background</p> <p>Ring species, exemplified by salamanders of the <it>Ensatina eschscholtzii </it>complex, represent a special window into the speciation process because they allow the history of species formation to be traced back in time through the geographically differentiated forms connecting the two terminal forms of the ring. Of particular interest is the nature and extent of reproductive isolation between the geographically terminal forms, in this case <it>E. e. eschscholtzii </it>and <it>E. e. klauberi</it>. Previous studies have documented infrequent hybridization at the end of the ring. Here, we report the first fine-scale genetic analysis of a hybrid zone between the terminal forms in southern California using individual-based Bayesian analyses of multilocus genetic data to estimate levels and direction of hybridization and maximum-likelihood analysis of linkage disequilibrium and cline shape to make inferences about migration and selection in the hybrid zone.</p> <p>Results</p> <p>The center of the hybrid zone has a high proportion of hybrids, about half of which were classified as F1s. Clines are narrow with respect to dispersal, and there are significant deviations from Hardy-Weinberg equilibrium as well as nonrandom associations (linkage disequilibria) between alleles characteristic of each parental type. There is cytonuclear discordance, both in terms of introgression and the geographic position of mitochondrial versus nuclear clines. Genetic disequilibrium is concentrated on the <it>eschscholtzii </it>side of the zone. Nearly all hybrids possess <it>klauberi </it>mtDNA, indicating that most hybrids are formed from female <it>klauberi </it>mating with male <it>eschscholtzii </it>or male hybrids (but not vice versa).</p> <p>Conclusions</p> <p>Our results are consistent with a tension zone trapped at an ecotone, with gene combinations characteristic of <it>klauberi </it>showing up on the <it>eschscholtzii </it>side of the zone due to asymmetric hybridization. We suggest that the observed asymmetry is best explained by increased discriminatory power of <it>eschscholtzii </it>females, or asymmetric postzygotic isolation. The relatively high frequency of hybrids, particularly F1s, contrasts with other contacts between the terminal forms, and with other contacts between other divergent <it>Ensatina </it>lineages, highlighting the diverse outcomes of secondary contact within a single species complex.</p

The influence of mosquito resting behaviour and associated microclimate for malaria risk

<p>Abstract</p> <p>Background</p> <p>The majority of the mosquito and parasite life-history traits that combine to determine malaria transmission intensity are temperature sensitive. In most cases, the process-based models used to estimate malaria risk and inform control and prevention strategies utilize measures of mean outdoor temperature. Evidence suggests, however, that certain malaria vectors can spend large parts of their adult life resting indoors.</p> <p>Presentation of hypothesis</p> <p>If significant proportions of mosquitoes are resting indoors and indoor conditions differ markedly from ambient conditions, simple use of outdoor temperatures will not provide reliable estimates of malaria transmission intensity. To date, few studies have quantified the differential effects of indoor <it>vs </it>outdoor temperatures explicitly, reflecting a lack of proper understanding of mosquito resting behaviour and associated microclimate.</p> <p>Testing the hypothesis</p> <p>Published records from 8 village sites in East Africa revealed temperatures to be warmer indoors than outdoors and to generally show less daily variation. Exploring the effects of these temperatures on malaria parasite development rate suggested indoor-resting mosquitoes could transmit malaria between 0.3 and 22.5 days earlier than outdoor-resting mosquitoes. These differences translate to increases in transmission risk ranging from 5 to approaching 3,000%, relative to predictions based on outdoor temperatures. The pattern appears robust for low- and highland areas, with differences increasing with altitude.</p> <p>Implications of the hypothesis</p> <p>Differences in indoor <it>vs </it>outdoor environments lead to large differences in the limits and the intensity of malaria transmission. This finding highlights a need to better understand mosquito resting behaviour and the associated microclimate, and to broaden assessments of transmission ecology and risk to consider the potentially important role of endophily.</p

Malaria in Africa: Vector Species' Niche Models and Relative Risk Maps

A central theoretical goal of epidemiology is the construction of spatial models of disease prevalence and risk, including maps for the potential spread of infectious disease. We provide three continent-wide maps representing the relative risk of malaria in Africa based on ecological niche models of vector species and risk analysis at a spatial resolution of 1 arc-minute (9 185 275 cells of approximately 4 sq km). Using a maximum entropy method we construct niche models for 10 malaria vector species based on species occurrence records since 1980, 19 climatic variables, altitude, and land cover data (in 14 classes). For seven vectors (Anopheles coustani, A. funestus, A. melas, A. merus, A. moucheti, A. nili, and A. paludis) these are the first published niche models. We predict that Central Africa has poor habitat for both A. arabiensis and A. gambiae, and that A. quadriannulatus and A. arabiensis have restricted habitats in Southern Africa as claimed by field experts in criticism of previous models. The results of the niche models are incorporated into three relative risk models which assume different ecological interactions between vector species. The “additive” model assumes no interaction; the “minimax” model assumes maximum relative risk due to any vector in a cell; and the “competitive exclusion” model assumes the relative risk that arises from the most suitable vector for a cell. All models include variable anthrophilicity of vectors and spatial variation in human population density. Relative risk maps are produced from these models. All models predict that human population density is the critical factor determining malaria risk. Our method of constructing relative risk maps is equally general. We discuss the limits of the relative risk maps reported here, and the additional data that are required for their improvement. The protocol developed here can be used for any other vector-borne disease

Beetroot supplementation improves the physiological responses to incline walking

The final publication is available at Springer via http://dx.doi.org/10.1007/s00421-018-3843-xPurpose: We investigated the effects of an acute 24-h nitrate-rich beetroot juice supplement (BR) on the energy cost, exercise efficiency and blood pressure responses to intermittent walking at different gradients. Methods: In a double-blind, cross-over design, eight participants were provided with a total of 350 ml of nitrate-rich (~20.5 mmol nitrate) BR or placebo (PLA) across 24-h before completing intermittent walking at 3 km/h on treadmill at gradients of 1%, 5%, 10%, 15% and 20%. Results: Resting mean arterial pressure (MAP) was ~4.1% lower after BR (93 vs. 89 mmHg; P = 0.001), as well as during exercise (102 vs. 99 mmHg; P = 0.011) and recovery (97 vs. 94 mmHg; P = 0.001). Exercising (1227 vs. 1129 ml/min P < 0.001) and end-stage (1404 vs. 1249 ml/min; P = 0.002) oxygen uptake (O2) was lower in BR compared to PLA, which was accompanied by an average reduction in phase II ̇O2 amplitude (1067 vs. 940 ml/min; P = 0.025). Similarly, recovery O2 (509 vs. 458 ml/min; P = 0.001) was lower in BR. Whole-blood potassium concentration increased from pre-post exercise in PLA (4.1 ± 0.3 vs. 4.5 ± 0.3 mmol/L; P = 0.013) but not BR (4.1 ± 0.31 vs. 4.3 ± 0.2 mmol/L; P = 0.188). Conclusions: Energy cost of exercise, recovery of O2, MAP and blood markers were ameliorated after BR. Previously reported mechanisms explain these findings, which are more noticeable during less efficient walking at steep gradients (15-20%). These findings have practical implications for hill-walkers

Chitosan gel vaccine protects against tumour growth in an intracaecal mouse model of cancer by modulating systemic immune responses.

Background Vaccination generating a robust memory population of CD8+ T cells may provide protection against cancer. However, immune therapies for cancer are influenced by the local tumour immune microenvironment. An infiltrate of T cells into tumours of people with colorectal cancer has proven to be a significant indicator of good prognosis. Methods We used an intracaecal mouse model of cancer to determine whether a protective immune response against a mucosal gut tumour could be generated using a systemic intervention. We investigated the generation of murine memory CD8+ T cells using a sustained antigen release vaccine vehicle (chitosan gel; Gel + OVA) containing the model antigen ovalbumin, chitosan gel alone (Gel) or conventional dendritic cell vaccination (DC + OVA) using the same protein antigen. Results Following vaccination with Gel + OVA, CD8+ T cell memory populations specific for ovalbumin protein were detected. Only vaccination with Gel + OVA gave decreased tumour burden compared to unvaccinated or DC + OVA-vaccinated mice in the intracaecal cancer challenge model. Conclusion These results indicate that subcutaneous vaccination with Gel + OVA generates a population of functional CD8+ memory T cells in lymphoid tissue able to protect against intracaecal tumour challenge. Vaccination with chitosan gel may be valuable in anti-cancer treatment at both peripheral and mucosal sites.</p