The effect of ethnicity on the vascular responses to cold exposure of the extremities

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 01/08/2014, available online: https://doi.org/10.1007/s00421-014-2962-2 The accepted version of the publication may differ from the final published version.© 2014, Springer-Verlag Berlin Heidelberg. Purpose: Cold injuries are more prevalent in individuals of African descent (AFD). Therefore, we investigated the effect of extremity cooling on skin blood flow (SkBF) and temperature (Tsk) between ethnic groups.Methods: Thirty males [10 Caucasian (CAU), 10 Asian (ASN), 10 AFD] undertook three tests in 30 °C air whilst digit Tsk and SkBF were measured: (i) vasomotor threshold (VT) test—arm immersed in 35 °C water progressively cooled to 10 °C and rewarmed to 35 °C to identify vasoconstriction and vasodilatation; (ii) cold-induced vasodilatation (CIVD) test—hand immersed in 8 °C water for 30 min followed by spontaneous warming; (iii) cold sensitivity (CS) test—foot immersed in 15 °C water for 2 min followed by spontaneous warming. Cold sensory thresholds of the forearm and finger were also assessed.Results: In the VT test, vasoconstriction and vasodilatation occurred at a warmer finger Tsk in AFD during cooling [21.2 (4.4) vs. 17.0 (3.1) °C, P = 0.034] and warming [22.0 (7.9) vs. 12.1 (4.1) °C, P = 0.002] compared with CAU. In the CIVD test, average SkBF during immersion was greater in CAU [42 (24) %] than ASN [25 (8) %, P = 0.036] and AFD [24 (13) %, P = 0.023]. Following immersion, SkBF was higher and rewarming faster in CAU [3.2 (0.4) °C min−1] compared with AFD [2.5 (0.7) °C min−1, P = 0.037], but neither group differed from ASN [3.0 (0.6) °C min−1]. Responses to the CS test and cold sensory thresholds were similar between groups.Conclusion: AFD experienced a more intense protracted finger vasoconstriction than CAU during hand immersion, whilst ASN experienced an intermediate response. This greater sensitivity to cold may explain why AFD are more susceptible to cold injuries.Published versio

Role of cyclooxygenase in the vascular response to locally delivered acetylcholine in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Elsevier in Microvascular Research on 17/01/2017, available online: https://doi.org/10.1016/j.mvr.2017.01.005 The accepted version of the publication may differ from the final published version.© 2017 Elsevier Inc. Introduction Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) compared with Caucasian individuals (CAU). Vasodilatation to acetylcholine (ACh) is lower in AFD compared with CAU in the non-glabrous foot and finger skin sites; the reason for this is unknown. Prostanoids are responsible, in part, for the vasodilator response to ACh, however it is not known whether the contribution differs between ethnicities. Methods 12 CAU and 12 AFD males received iontophoresis of ACh (1 w/v%) on non-glabrous foot and finger skin sites following placebo and then aspirin (600 mg, single blinded). Aspirin was utilised to inhibit prostanoid production by inhibiting the cyclooxygenase (COX) enzyme. Laser Doppler flowmetry was utilised to measure changes in skin blood flow. Results Not all participants could receive iontophoresis charge due to high skin resistance; these participants were therefore excluded from the analyses. Foot: ACh elicited greater maximal vasodilatation in CAU than AFD following placebo (P = 0.003) and COX inhibition (COXib) (P < 0.001). COXib did not affect blood flow responses in AFD, but caused a reduction in the area under the curve for CAU (P = 0.031). Finger: ACh elicited a greater maximal vasodilatation in CAU than AFD following placebo (P = 0.013) and COXib (P = 0.001). COXib tended to reduce the area under the curve in AFD (P = 0.053), but did not affect CAU. Conclusions CAU have a greater endothelial reactivity than AFD in both foot and finger skin sites irrespective of COXib. It is concluded that the lower ACh-induced vasodilatation in AFD is not due to a compromised COX pathway.Published versio

Environmental stress alters genetic regulation of novelty seeking in vervet monkeys.

Considerable attention has been paid to identifying genetic influences and gene-environment interactions that increase vulnerability to environmental stressors, with promising but inconsistent results. A nonhuman primate model is presented here that allows assessment of genetic influences in response to a stressful life event for a behavioural trait with relevance for psychopathology. Genetic and environmental influences on free-choice novelty seeking behaviour were assessed in a pedigreed colony of vervet monkeys before and after relocation from a low stress to a higher stress environment. Heritability of novelty seeking scores, and genetic correlations within and between environments were conducted using variance components analysis. The results showed that novelty seeking was markedly inhibited in the higher stress environment, with effects persisting across a 2-year period for adults but not for juveniles. There were significant genetic contributions to novelty seeking scores in each year (h(2) = 0.35-0.43), with high genetic correlations within each environment (rhoG &gt; 0.80) and a lower genetic correlation (rhoG = 0.35, non-significant) between environments. There were also significant genetic contributions to individual change scores from before to after the move (h(2) = 0.48). These results indicate that genetic regulation of novelty seeking was modified by the level of environmental stress, and they support a role for gene-environment interactions in a behavioural trait with relevance for mental health

Design and fabrication of a mid infra-red photonic crystal defect laser in indium antimonide

This paper presents 2D FDTD modelling and prototype fabrication of a mid-infrared photonic crystal defect laser. The device is fabricated using a two stage Focused Ion Beam process which results in improved hole profiles

Ecology of common bully (Gobiomorphus cotidianus) in the Tarawera and Rangitaiki rivers: isolation by inland distance or anthropogenic discharge?

Previous research has identified distinct genetic, life-history and reproductive differences between populations of common bully (Gobiomorphus cotidianus) upstream and downstream of a pulp and paper mill outfall on the Tarawera River in the Bay of Plenty, New Zealand. This study investigated the distribution of common bully in the Tarawera River by examining fish collected from upstream (37 km inland) and downstream (20 km inland) locations and comparing them to fish from similar inland locations (40 km and 17 km inland, respectively) in the nearby Rangitaiki River. Reproductive divergence was observed between upstream and downstream sites of both rivers by differing annual trends in gonadosomatic index. Stable carbon and nitrogen isotopes confirmed residency at each sampling site and otolith microchemistry demonstrated different life-history strategies between upstream and downstream populations. Diadromous recruits dominated in both downstream river populations, with a general disappearance of diadromy upstream. A mixture of diadromous and non-diadromous fish were found in the upstream Rangitaiki River, whereas diadromous recruits were absent in the upstream Tarawera River. A reduction in oculoscapular canal structures also coincided with loss of diadromy in fish from both rivers. A behavioural study to determine whether pulp and paper mill effluent may deter fish migration within the Tarawera River demonstrated a strong avoidance of effluent, but only at concentrations (>25%) greater than those that naturally occur in the river (<15%). The results of this study suggest that combinations of influences coupled with inland distance are likely to be responsible for the isolation of common bully subpopulations within the Tarawera River

Problems, successes and challenges for the application of dispersion-corrected density-functional theory combined with dispersion-based implicit solvent models to large-scale hydrophobic self-assembly and polymorphism

© 2015 Taylor & Francis. The recent advent of dispersion-corrected density-functional theory (DFT) methods allows for quantitative modelling of molecular self-assembly processes, and we consider what is required to develop applications to the formation of large self-assembled monolayers (SAMs) on hydrophobic surfaces from organic solution. Focus is on application of the D3 dispersion correction of Grimme combined with the solvent dispersion model of Floris, Tomasi and Pascual-Ahuir to simulate observed scanning-tunnelling microscopy (STM) images of various polymorphs of tetraalkylporphyrin SAMs on highly oriented pyrolytic graphite surfaces. The most significant problem is identified as the need to treat SAM structures that are incommensurate with those of the substrate, providing a challenge to the use of traditional periodic-imaging boundary techniques. Using nearby commensurate lattices introduces non-systematic errors into calculated lattice constants and free energies of SAM formation that are larger than experimental uncertainties and polymorph differences. Developing non-periodic methods for polymorph interface simulation also remains a challenge. Despite these problems, existing methods can be used to interpret STM images and SAM atomic structures, distinguishing between multiple feasible polymorph types. They also provide critical insight into the factors controlling polymorphism. All this stems from a delicate balance that the intermolecular D3 and solvent Floris, Tomasi and Pascual-Ahuir corrections provide. Combined optimised treatments should yield fully quantitative approaches in the future

Continuous Time Modelling Based on an Exact Discrete Time Representation

This chapter provides a survey of methods of continuous time modelling based on an exact discrete time representation. It begins by highlighting the techniques involved with the derivation of an exact discrete time representation of an underlying continuous time model,providing specificc details for a second-order linear system of stochastic differential equations. Issues of parameter identification, Granger causality, nonstationarity, and mixed frequency data are addressed, all being important considerations in applications in economics and other disciplines. Although the focus is on Gaussian estimation of the exact discrete time model, alternative time domain (state space) and frequency domain approaches are also discussed. Computational issues are explored and two new empirical applications are included along with a discussion of applications in the field of macroeconometric modelling

Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy?

This is the final version. Available on open access from Elsevier via the DOI in this recordAt least one-third of all people with epilepsy have seizures that remain poorly controlled despite an increasing number of available anti-epileptic drugs (AEDs). Often, there is an initial good response to a newly introduced AED, which may last up to months, eventually followed by the return of seizures thought to be due to the development of tolerance. We introduce a framework within which the interplay between AED response and brain networks can be explored to understand the development of tolerance. We use a computer model for seizure generation in the context of dynamic networks, which allows us to generate an ‘in silico’ electroencephalogram (EEG). This allows us to study the effect of changes in excitability network structure and intrinsic model properties on the overall seizure likelihood. Within this framework, tolerance to AEDs – return of seizure-like activity – may occur in 3 different scenarios: 1) the efficacy of the drug diminishes while the brain network remains relatively constant; 2) the efficacy of the drug remains constant, but connections between brain regions change; 3) the efficacy of the drug remains constant, but the intrinsic excitability within brain regions varies dynamically. We argue that these latter scenarios may contribute to a deeper understanding of how drug resistance to AEDs may occur.Medical Research Council (MRC)Royal SocietyWellcome TrustEngineering and Physical Sciences Research Council (EPSRC