Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescentlylabelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188-expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.This study is funded by the Cancer Research UK

SAT-based Explicit LTL Reasoning

We present here a new explicit reasoning framework for linear temporal logic (LTL), which is built on top of propositional satisfiability (SAT) solving. As a proof-of-concept of this framework, we describe a new LTL satisfiability tool, Aalta\_v2.0, which is built on top of the MiniSAT SAT solver. We test the effectiveness of this approach by demonnstrating that Aalta\_v2.0 significantly outperforms all existing LTL satisfiability solvers. Furthermore, we show that the framework can be extended from propositional LTL to assertional LTL (where we allow theory atoms), by replacing MiniSAT with the Z3 SMT solver, and demonstrating that this can yield an exponential improvement in performance

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

Anisotropic field dependence of the magnetic transition in Cu2Te2O5Br2

We present the results of measurements of the thermal conductivity of Cu2Te2O5Br2, a compound where tetrahedra of Cu^{2+} ions carrying S=1/2 spins form chains along the c-axis of the tetragonal crystal structure. The thermal conductivity kappa was measured along both the c- and the a-direction as a function of temperature between 3 and 300 K and in external magnetic fields H up to 69 kOe, oriented both parallel and perpendicular to the c-axis. Distinct features of kappa(T) were observed in the vicinity of T_N=11.4 K in zero magnetic field. These features are unaltered in external fields which are parallel to the c-axis, but are more pronounced when a field is applied perpendicularly to the c-axis. The transition temperature increases upon enhancing the external field, but only if the field is oriented along the a-axis.Comment: 5 pages, 3 figure

Alcohol Production as an Adaptive Livelihood Strategy for Women Farmers in Tanzania and Its Potential for Unintended Consequences on Women's Reproductive Health.

Although women occupy a central position in agriculture in many developing countries, they face numerous constraints to achieving their full potential including unequal access to assets and limited decision-making authority. We explore the intersection of agricultural livelihoods, food and economic security, and women's sexual and reproductive health in Iringa Region, Tanzania. Our goal was to understand whether the benefits of supporting women in the agricultural sector might also extend to more distal outcomes, including sexual and reproductive health. Using the Sustainable Livelihoods Framework to guide data collection, we conducted 13 focus group discussions (FGD) with female (n = 11) and male farmers (n = 2) and 20 in-depth interviews with agricultural extension officers (n = 10) and village agro-dealers (n = 10). Despite providing the majority of agricultural labor, women have limited control over land and earned income and have little bargaining power. In response to these constraints, women adopt adaptive livelihood strategies, such as alcohol production, that allow them to retain control over income and support their households. However, women's central role in alcohol production, in concert with the ubiquitous nature of alcohol consumption, places them at risk by enhancing their vulnerability to unsafe or transactional sex. This represents a dangerous confluence of risk for female farmers, in which alcohol plays an important role in income generation and also facilitates high-risk sexual behavior. Alcohol production and consumption has the potential to both directly and indirectly place women at risk for undesirable sexual and reproductive health outcomes. Group formation, better access to finance, and engaging with agricultural extension officers were identified as potential interventions for supporting women farmers and challenging harmful gender norms. In addition, joint, multi-sectoral approaches from health and agriculture and alternative income-generating strategies for women might better address the complexities of achieving safe and sustainable livelihoods for women in this context

Tamoxifen-associated vasculitis in a breast cancer patient

BACKGROUND: Estrogen plays a critical role in breast cancer. Thereafter, endocrine therapy is a standard of care in patients with breast carcinoma, expressing ER or PR. CASE PRESENTATION: Herein we report the case of a 53-year old patient, who developed cholestasis and vasculitis during the treatment with tamoxifen. This toxicity was reversable after the removal of the drug. Thereafter she continued adjuvant treatment for breast carcinoma with anastrazole. Since tamoxifen has been widely indicated for patients with breast carcinoma, we did a literature review, looking for other cases with this type of toxicity. CONCLUSION: This case is the third with vasculitis informed in the literature, but the first one that additionally developed cholestasis and arthritis. Although it is rare, we discuss the indication of this drug in the actual era, where aromatase inhibitors offer a better security profile

Effect of floor type on the performance, physiological and behavioural responses of finishing beef steers

peer-reviewedBackground:The study objective was to investigate the effect of bare concrete slats (Control), two types of mats [(Easyfix mats (mat 1) and Irish Custom Extruder mats (mat 2)] fitted on top of concrete slats, and wood-chip to simulate deep bedding (wood-chip placed on top of a plastic membrane overlying the concrete slats) on performance, physiological and behavioral responses of finishing beef steers. One-hundred and forty-four finishing steers (503 kg; standard deviation 51.8 kg) were randomly assigned according to their breed (124 Continental cross and 20 Holstein–Friesian) and body weight to one of four treatments for 148 days. All steers were subjected to the same weighing, blood sampling (jugular venipuncture), dirt and hoof scoring pre study (day 0) and on days 23, 45, 65, 86, 107, 128 and 148 of the study. Cameras were fitted over each pen for 72 h recording over five periods and subsequent 10 min sampling scans were analysed. Results: Live weight gain and carcass characteristics were similar among treatments. The number of lesions on the hooves of the animals was greater (P < 0.05) on mats 1 and 2 and wood-chip treatments compared with the animals on the slats. Dirt scores were similar for the mat and slat treatments while the wood-chip treatment had greater dirt scores. Animals housed on either slats or wood-chip had similar lying times. The percent of animals lying was greater for animals housed on mat 1 and mat 2 compared with those housed on concrete slats and wood chips. Physiological variables showed no significant difference among treatments. Conclusions: In this exploratory study, the performance or welfare of steers was not adversely affected by slats, differing mat types or wood-chip as underfoot material

Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging