The local evaluation of Halton's Healthy Living programme annual reach report, August 2004 - July 2005

This project report discusses an evaluation of the services of Halton's Healthy Living Centre, which aims to promote good health, reduce health inequalities, and improve the health of the most disadvantaged in Halton

A Dance That Creates Equals: Unpacking Leadership Development

Our cooperative inquiry focused on the question "How can we create the space/opportunities for individuals to recognize themselves as leaders and develop leadership?" Early on, our group realized that we were not referring to leadership as an individual act as is traditionally the case. Instead, most of the stories we shared throughout our inquiry dealt with the details of close working relationships with people in our organizations and communities.Exploring what must happen for leadership to be shared led us to see the need to encourage a genuine shift in the leadership relationship, in which someone steps back (whether they do it consciously or not) and someone steps up. (In our conversations we've termed the latter crossing over.) We are very clear that these two actions are linked but are not necessarily sequential

Do Pareto-Zipf and Gibrat laws hold true? An analysis with European Firms

By employing exhaustive lists of large firms in European countries, we show that the upper-tail of the distribution of firm size can be fitted with a power-law (Pareto-Zipf law), and that in this region the growth rate of each firm is independent of the firm's size (Gibrat's law of proportionate effect). We also find that detailed balance holds in the large-size region for periods we investigated; the empirical probability for a firm to change its size from a value to another is statistically the same as that for its reverse process. We prove several relationships among Pareto-Zipf's law, Gibrat's law and the condition of detailed balance. As a consequence, we show that the distribution of growth rate possesses a non-trivial relation between the positive side of the distribution and the negative side, through the value of Pareto index, as is confirmed empirically

On waiting for something to happen

This paper seeks to examine two particular and peculiar practices in which the mediation of apparently direct encounters is made explicit and is systematically theorized: that of the psychoanalytic dialogue with its inward focus and private secluded setting, and that of theatre and live performance, with its public focus. Both these practices are concerned with ways in which “live encounters” impact on their participants, and hence with the conditions under which, and the processes whereby, the coming-together of human subjects results in recognizable personal or social change. Through the rudimentary analysis of two anecdotes, we aim to think these encounters together in a way that explores what each borrows from the other, the psychoanalytic in the theatrical, the theatrical in the psychoanalytic, figuring each practice as differently committed to what we call the “publication of liveness”. We argue that these “redundant” forms of human contact continue to provide respite from group acceptance of narcissistic failure in the post-democratic era through their offer of a practice of waiting

Efficacy and Safety of High-Dose Ivermectin for Reducing Malaria Transmission (IVERMAL): Protocol for a Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Trial in Western Kenya

Background: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150‐200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150‐200 mcg/kg oral dose is short‐lived (6‐11 days). Modelling suggests higher doses, that prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination. Ivermectin has a wide therapeutic index and previous studies have shown doses up to 2,000 mcg/kg, i.e. 10x the US Food and Drug Administration approved dose, are well tolerated and safe; the highest dose used for onchocerciasis is single‐dose 800 mcg/kg. Objective: To determine the safety, tolerability, and efficacy of ivermectin 0, 300, 600 mcg/kg/day for 3 days, when provided with a standard 3‐day course of the antimalarial dihydroartemisinin‐piperaquine, on mosquito survival. Methods: This is a double‐blind, randomised, placebo‐controlled, parallel‐group, 3‐arm, dose‐finding trial in adults with uncomplicated malaria. Monte Carlo simulations based on pharmacokinetic modelling were performed to determine the optimum dosing regimens to be tested. Modelling showed that a 3‐day regimen of 600 mcg/kg/day achieves similar median (5‐95 percentiles) Cmax concentrations of ivermectin to single‐dose of 800 mcg/kg, while increasing the median time above the LC50 (16 ng/mL) from 1.9 days (1.0‐5.7) to 6.8 (3.8‐13.4) days. The 300 mcg/kg/day dose was chosen at 50% of the higher dose to allow evaluation of the dose response. Mosquito survival will be assessed daily up to 28 days in laboratory‐reared Anopheles gambiae s.s. populations fed on patients’ blood taken at days 0, 2 (Cmax), 7 (primary outcome), 10, 14, 21, and 28 after the start of treatment. Safety outcomes include QT‐prolongation and mydriasis. The trial will be conducted in 6 health facilities in western Kenya and requires a sample size of 141 participants (47 per arm). Sub‐studies include: (1) rich pharmacokinetics and (2) direct skin vs membrane feeding assays. Results: Recruitment started July 20th, 2015. Data collection was completed on July 2nd, 2016. Unblinding and analysis will commence once the database has been completed, cleaned and locked. Discussion: High‐dose ivermectin, if found to be safe and well tolerated, might offer a promising new tool for malaria elimination. Trial registration: ClinicalTrials.gov: NCT02511353 (July 15, 2015)

The intersection between Descriptivism and Meliorism in reasoning research: further proposals in support of 'soft normativism'

The rationality paradox centres on the observation that people are highly intelligent, yet show evidence of errors and biases in their thinking when measured against normative standards. Elqayam and Evans (e.g., 2011) reject normative standards in the psychological study of thinking, reasoning and deciding in favour of a ‘value-free’ descriptive approach to studying high-level cognition. In reviewing Elqayam and Evans’ position, we defend an alternative to descriptivism in the form of ‘soft normativism’, which allows for normative evaluations alongside the pursuit of descriptive research goals. We propose that normative theories have considerable value provided that researchers: (1) are alert to the philosophical quagmire of strong relativism; (2) are mindful of the biases that can arise from utilising normative benchmarks; and (3) engage in a focused analysis of the processing approach adopted by individual reasoners. We address the controversial ‘is–ought’ inference in this context and appeal to a ‘bridging solution’ to this contested inference that is based on the concept of ‘informal reflective equilibrium’. Furthermore, we draw on Elqayam and Evans’ recognition of a role for normative benchmarks in research programmes that are devised to enhance reasoning performance and we argue that such Meliorist research programmes have a valuable reciprocal relationship with descriptivist accounts of reasoning. In sum, we believe that descriptions of reasoning processes are fundamentally enriched by evaluations of reasoning quality, and argue that if such standards are discarded altogether then our explanations and descriptions of reasoning processes are severely undermined

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Definition of an inflammatory biomarker signature in plasma-derived extracellular vesicles of glioblastoma patients

Glioblastoma (GB) is an aggressive type of tumour for which therapeutic options and biomarkers are limited. GB diagnosis mostly relies on symptomatic presentation of the tumour and, in turn, brain imaging and invasive biopsy that can delay its diagnosis. Description of easily accessible and effective biomarkers present in biofluids would thus prove invaluable in GB diagnosis. Extracellular vesicles (EVs) derived from both GB and stromal cells are essential to intercellular crosstalk in the tumour bulk, and circulating EVs have been described as a potential reservoir of GB biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GB diagnosis and follow up. To identify GB specific proteins, sEVs were isolated from plasma samples of GB patients as well as healthy volunteers using differential ultracentrifugation, and their content was characterised through mass spectrometry. Our data indicate the presence of an inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Overall, this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GB diagnosis and, consequently, patients’ prognosis and quality of life