Oxygen consumption dynamics in steady-state tumour models

Oxygen levels in cancerous tissue can have a significant effect on treatment response: hypoxic tissue is both more radioresistant and more chemoresistant than well-oxygenated tissue. While recent advances in medical imaging have facilitated real-time observation of macroscopic oxygenation, the underlying physics limits the resolution to the millimetre domain, whereas oxygen tension varies over a micrometre scale. If the distribution of oxygen in the tumour micro-environment can be accurately estimated, then the effect of potential dose escalation to these hypoxic regions could be better modelled, allowing more realistic simulation of biologically adaptive treatments. Reaction-diffusion models are commonly used for modelling oxygen dynamics, with a variety of functional forms assumed for the dependence of oxygen consumption rate (OCR) on cellular status and local oxygen availability. In this work, we examine reaction-diffusion models of oxygen consumption in spherically and cylindrically symmetric geometries. We consider two different descriptions of oxygen consumption: one in which the rate of consumption is constant and one in which it varies with oxygen tension in a hyperbolic manner. In each case, we derive analytic approximations to the steady-state oxygen distribution, which are shown to closely match the numerical solutions of the equations and accurately predict the extent to which oxygen can diffuse. The derived expressions relate the limit to which oxygen can diffuse into a tissue to the OCR of that tissue. We also demonstrate that differences between these functional forms are likely to be negligible within the range of literature estimates of the hyperbolic oxygen constant, suggesting that the constant consumption rate approximation suffices for modelling oxygen dynamics for most values of OCR. These approximations also allow the rapid identification of situations where hyperbolic consumption forms can result in significant differences from constant consumption rate models, and so can reduce the computational workload associated with numerical solutions, by estimating both the oxygen diffusion distances and resultant oxygen profile. Such analysis may be useful for parameter fitting in large imaging datasets and histological sections, and allows easy quantification of projected differences between functional forms of OCR

Decomposition process in a FeAuPd alloy nanostructured by severe plastic deformation

The decomposition process mechanisms have been investigated in a Fe50Au25Pd25 (at.%) alloy processed by severe plastic deformation. Phases were characterized by X-ray diffraction and microstructures were observed using transmission electron microscopy. In the coarse grain alloy homogenized and aged at $450 ^{circ}\mathrm{C}$, the bcc \alpha-Fe and fcc AuPd phases nucleate in the fcc supersaturated solid solution and grow by a discontinuous precipitation process resulting in a typical lamellar structure. The grain size of the homogenized FeAuPd alloy was reduced in a range of 50 to 100nm by high pressure torsion. Aging at $450 ^{circ}\mathrm{C}$ this nanostructure leads to the decomposition of the solid solution into an equi-axed microstructure. The grain growth is very limited during aging and the grain size remains under 100nm. The combination of two phases with different crystallographic structures (bcc \alpha-Fe and fcc AuPd) and of the nanoscaled grain size gives rise to a significant hardening of the allo

A model for reactive porous transport during re-wetting of hardened concrete

A mathematical model is developed that captures the transport of liquid water in hardened concrete, as well as the chemical reactions that occur between the imbibed water and the residual calcium silicate compounds residing in the porous concrete matrix. The main hypothesis in this model is that the reaction product -- calcium silicate hydrate gel -- clogs the pores within the concrete thereby hindering water transport. Numerical simulations are employed to determine the sensitivity of the model solution to changes in various physical parameters, and compare to experimental results available in the literature.Comment: 30 page

The patient burden of opioid-induced constipation: New insights from a large, multinational survey in five European countries

BACKGROUND: Despite its high prevalence, opioid-induced constipation (OIC) remains under-recognised and undertreated, and its true impact on wellbeing and quality of life (QoL) may be underestimated. METHODS: A quantitative, questionnaire-based international survey was conducted. RESULTS: Weak-opioid users appeared as bothered by constipation as strong-opioid users (38% vs 40%, respectively; p = 0.40), despite it causing less-severe physical symptoms and impact on QoL. Strong-opioid users meeting Rome IV OIC criteria appeared to experience greater symptomatic and biopsychosocial burden from constipation than those not satisfying these criteria. Almost one-fifth of respondents were dissatisfied with their current constipation treatment and around one-third found balancing the need for adequate pain relief with constipation side effects challenging. Consequently, more than half failed to adhere to their prescribed treatment regimens, or resorted to suboptimal strategies, e.g. 40% reduced their opioid intake, to relieve constipation. Almost 60% of healthcare professionals did not adequately counsel patients about constipation as a common side effect of opioid use. CONCLUSIONS: Findings suggest that both weak- and strong-opioid users suffer comparable bother and decreased QoL, Rome IV criteria can identify patients with more-severe OIC, but may underdiagnose patients showing fewer symptoms, and increased education is needed to manage patients’ expectations and enable improved OIC self-management

EWPD Constraints on Flavor Symmetric Vector Fields

Electroweak precision data constraints on flavor symmetric vector fields are determined. The flavor multiplets of spin one that we examine are the complete set of fields that couple to quark bi-linears at tree level while not initially breaking the quark global flavor symmetry group. Flavor safe vector masses proximate to, and in some cases below, the electroweak symmetry breaking scale are found to be allowed. Many of these fields provide a flavor safe mechanism to explain the t tbar forward backward anomaly, and can simultaneously significantly raise the allowed values of the Standard Model Higgs mass consistent with electroweak precision data.Comment: Matches version published in JHE

Color & Weak triplet scalars, the dimuon asymmetry in BsB_s decay, the top forward-backward asymmetry, and the CDF dijet excess

The new physics required to explain the anomalies recently reported by the D0 and CDF collaborations, namely the top forward-backward asymmetry (FBA), the like-sign dimuon charge asymmetry in semileptonic b decay, and the CDF dijet excess, has to feature an amount of flavor symmetry in order to satisfy the severe constrains arising from flavor violation. In this paper we show that, once baryon number conservation is imposed, color & weak triplet scalars with hypercharge $Y=1/3$ can feature the required flavor structure as a consequence of standard model gauge invariance. The color & weak triplet model can simultaneously explain the top FBA and the dimuon charge asymmetry or the dimuon charge asymmetry and the CDF dijet excess. However, the CDF dijet excess appears to be incompatible with the top FBA in the minimal framework. Our model for the dimuon asymmetry predicts the observed pattern $h_d\ll h_s$ in the region of parameter space required to explain the top FBA, whereas our model for the CDF dijet anomaly is characterized by the absence of beyond the SM b-quark jets in the excess region. Compatibility of the color & weak triplet with the electroweak constraints is also discussed. We show that a Higgs boson mass exceeding the LEP bound is typically favored in this scenario, and that both Higgs production and decay can be significantly altered by the triplet. The most promising collider signature is found if the splitting among the components of the triplet is of weak scale magnitude.Comment: references added, published versio

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

On theories of enhanced CP violation in B_s,d meson mixing

The DO collaboration has measured a deviation from the standard model (SM) prediction in the like sign dimuon asymmetry in semileptonic b decay with a significance of 3.2 sigma. We discuss how minimal flavour violating (MFV) models with multiple scalar representations can lead to this deviation through tree level exchanges of new MFV scalars. We review how the two scalar doublet model can accommodate this result and discuss some of its phenomenology. Limits on electric dipole moments suggest that in this model the coupling of the charged scalar to the right handed u-type quarks is suppressed while its coupling to the d-type right handed quarks must be enhanced. We construct an extension of the MFV two scalar doublet model where this occurs naturally.Comment: 10 pages, 7 figures, v3 final JHEP versio

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD