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

Beyond clustering: mean-field dynamics on networks with arbitrary subgraph composition

Clustering is the propensity of nodes that share a common neighbour to be connected. It is ubiquitous in many networks but poses many modelling challenges. Clustering typically manifests itself by a higher than expected frequency of triangles, and this has led to the principle of constructing networks from such building blocks. This approach has been generalised to networks being constructed from a set of more exotic subgraphs. As long as these are fully connected, it is then possible to derive mean-field models that approximate epidemic dynamics well. However, there are virtually no results for non-fully connected subgraphs. In this paper, we provide a general and automated approach to deriving a set of ordinary differential equations, or mean-field model, that describes, to a high degree of accuracy, the expected values of system-level quantities, such as the prevalence of infection. Our approach offers a previously unattainable degree of control over the arrangement of subgraphs and network characteristics such as classical node degree, variance and clustering. The combination of these features makes it possible to generate families of networks with different subgraph compositions while keeping classical network metrics constant. Using our approach, we show that higher-order structure realised either through the introduction of loops of different sizes or by generating networks based on different subgraphs but with identical degree distribution and clustering, leads to non-negligible differences in epidemic dynamics

The impact of contact tracing in clustered populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease

Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects

Dynamics of multi-stage infections on networks

This paper investigates the dynamics of infectious diseases with a nonexponentially distributed infectious period. This is achieved by considering a multistage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider

Consistent approximation of epidemic dynamics on degree-heterogeneous clustered networks

Realistic human contact networks capable of spreading infectious disease, for example studied in social contact surveys, exhibit both significant degree heterogeneity and clustering, both of which greatly affect epidemic dynamics. To understand the joint effects of these two network properties on epidemic dynamics, the effective degree model of Lindquist et al. [28] is reformulated with a new moment closure to apply to highly clustered networks. A simulation study comparing alternative ODE models and stochastic simulations is performed for SIR (Susceptible–Infected–Removed) epidemic dynamics, including a test for the conjectured error behaviour in [40], providing evidence that this novel model can be a more accurate approximation to epidemic dynamics on complex networks than existing approaches

Heterotic strings on G_2 orbifolds

We study compactification of heterotic strings to three dimensions on orbifolds of G_2 holonomy. We consider the standard embedding and show that the gauge group is broken from E_8 x E_8 or SO(32) to F_4 x E_8 or SO(25) respectively. We also compute the spectrum of massless states and compare with the results obtained from reduction of the 10-dimensional fields. Non-standard embeddings are discussed briefly. For type II compactifications we verify that IIB and IIA have equal massless spectrum.Comment: LaTex, 21 page

A randomised controlled trial to assess the effectiveness of a single session of nurse administered massage for short term relief of chronic non-malignant pain

Background: Massage is increasingly used to manage chronic pain but its benefit has not been clearly established. The aim of the study is to determine the effectiveness of a single session of nurse-administered massage for the short term relief of chronic non-malignant pain and anxiety. Methods: A randomised controlled trial design was used, in which the patients were assigned to a massage or control group. The massage group received a 15 minute manual massage and the control group a 15 minute visit to talk about their pain. Adult patients attending a pain relief unit with a diagnosis of chronic pain whose pain was described as moderate or severe were eligible for the study. An observer blind to the patients' treatment group carried out assessments immediately before (baseline), after treatment and 1, 2, 3 and 4 hours later. Pain was assessed using 100 mm visual analogue scale and the McGill Pain Questionnaire. Pain Relief was assessed using a five point verbal rating scale. Anxiety was assessed with the Spielberger short form State-Trait Anxiety Inventory. Results: 101 patients were randomised and evaluated, 50 in the massage and 51 in the control group. There were no statistically significant differences between the groups at baseline interview. Patients in the massage but not the control group had significantly less pain compared to baseline immediately after and one hour post treatment. 95% confidence interval for the difference in mean pain reduction at one hour post treatment between the massage and control groups is 5.47 mm to 24.70 mm. Patients in the massage but not the control group had a statistically significant reduction in anxiety compared to baseline immediately after and at 1 hour post treatment. Conclusion: Massage is effective in the short term for chronic pain of moderate to severe intensity