518 research outputs found
The transgenic expression of LARGE exacerbates the muscle phenotype of dystroglycanopathy mice
Metformin Treatment Has No Beneficial Effect in a Dose-Response Survival Study in the SOD1G93A Mouse Model of ALS and Is Harmful in Female Mice
Background: Amyotrophic Lateral Sclerosis (ALS) is a devastating neurological disorder characterized by selective
degeneration of upper and lower motor neurons. The primary triggers for motor neuron degeneration are unknown but
inflammation, oxidative stress and mitochondrial defects have been identified as potential contributing factors. Metformin is
an anti-type II diabetes drug that has anti-inflammatory and anti-oxidant properties, can bring about mitochondrial
biogenesis and has been shown to attenuate pathology in mouse models of Huntington’s disease and multiple sclerosis. We
therefore hypothesized that it might increase survival in the SOD1G93A murine model of ALS.
Methodology/Principal Findings: Treatment of male and female SOD1G93A mice (n = 14 per sex). Results for all groups were
compared using Kaplan-Meier time to event analyses. In this survival study, metformin was unable to reduce pathology at
any dose and had an unexpected dose-dependent negative effect on the onset of neurological symptoms (P = 0.0236) and
on disease progression (P = 0.0362) in female mice.
Conclusions/Significance: This study suggests that metformin is a poor candidate for clinical trial in ALS patients and that
the possibility of harmful effects of metformin in female ALS patients with type II diabetes should be investigated
Parity-Violating Excitation of the \Delta(1232): Hadron Structure and New Physics
We consider prospects for studying the parity-violating (PV) electroweak
excitation of the \Delta(1232) resonance with polarized electron scattering.
Given present knowledge of Standard Model parameters, such PV experiments could
allow a determination of the N -> \Delta electroweak helicity amplitudes. We
discuss the experimental feasibility and theoretical interpretability of such a
determination as well as the prospective implications for hadron structure
theory. We also analyze the extent to which a PV N -> \Delta measurement could
constrain various extensions of the Standard Model.Comment: 43 pages, RevTex, 8 PS figures, uses epsf.sty, rotate.sty, version to
appear in Nucl. Phys. A, main points emphasized, some typos correcte
R_b and New Physics: A Comprehensive Analysis
We survey the implications for new physics of the discrepancy between the LEP
measurement of and its Standard Model prediction. Two broad classes of
models are considered: () those in which new Z\bbar b couplings arise at
tree level, through or -quark mixing with new particles, and ()
those in which new scalars and fermions alter the Z \bbar b vertex at one
loop. We keep our analysis as general as possible in order to systematically
determine what kinds of features can produce corrections to of the right
sign and magnitude. We are able to identify several successful mechanisms,
which include most of those which have been recently been proposed in the
literature, as well as some earlier proposals (\eg\ supersymmetric models). By
seeing how such models appear as special cases of our general treatment we are
able to shed light on the reason for, and the robustness of, their ability to
explain .Comment: 60 pages, 8 figures, plain tex, uses epsf. Final version to appear in
Phys. Rev. D; propgating sign error corrected in eqs. 78, 87, 88, 89, 98, and
107; results unchange
Exposing the myths of household water insecurity in the global north: A critical review
Safe and secure water is a cornerstone of modern life in the global North. This article critically examines a set of prevalent myths about household water in high-income countries, with a focus on Canada and the United States. Taking a relational approach, we argue that household water insecurity is a product of institutionalized structures and power, manifests unevenly through space and time, and is reproduced in places we tend to assume are the most water-secure in the world. We first briefly introduce “modern water” and the modern infrastructural ideal, a highly influential set of ideas that have shaped household water provision and infrastructure development over the past two centuries. Against this backdrop, we consolidate evidence to disrupt a set of narratives about water in high-income countries: the notion that water access is universal, clean, affordable, trustworthy, and uniformly or equitably governed. We identify five thematic areas of future research to delineate an agenda for advancing scholarship and action—including challenges of legal and regulatory regimes, the housing-water nexus, water affordability, and water quality and contamination. Data gaps underpin the experiences of household water insecurity. Taken together, our review of water security for households in high-income countries provides a conceptual map to direct critical research in this area for the coming years
The Discovery Potential of a Super B Factory
The Proceedings of the 2003 SLAC Workshops on flavor physics with a high
luminosity asymmetric e+e- collider. The sensitivity of flavor physics to
physics beyond the Standard Model is addressed in detail, in the context of the
improvement of experimental measurements and theoretical calculations.Comment: 476 pages. Printed copies may be obtained by request to
[email protected] . arXiv admin note: v2 appears to be identical to v
Exposing the myths of household water insecurity in the global north: A critical review
Safe and secure water is a cornerstone of modern life in the global North. This article critically examines a set of prevalent myths about household water in high-income countries, with a focus on Canada and the United States. Taking a relational approach, we argue that household water insecurity is a product of institutionalized structures and power, manifests unevenly through space and time, and is reproduced in places we tend to assume are the most water-secure in the world. We first briefly introduce “modern water” and the modern infrastructural ideal, a highly influential set of ideas that have shaped household water provision and infrastructure development over the past two centuries. Against this backdrop, we consolidate evidence to disrupt a set of narratives about water in high-income countries: the notion that water access is universal, clean, affordable, trustworthy, and uniformly or equitably governed. We identify five thematic areas of future research to delineate an agenda for advancing scholarship and action—including challenges of legal and regulatory regimes, the housing-water nexus, water affordability, and water quality and contamination. Data gaps underpin the experiences of household water insecurity. Taken together, our review of water security for households in high-income countries provides a conceptual map to direct critical research in this area for the coming years. This article is categorized under: Human Water \u3e Human Water
Understanding the health and wellbeing challenges of the food banking system: A qualitative study of food bank users, providers and referrers in London.
In the UK, food poverty has been associated with conditions such as obesity, malnutrition, hypertension, iron deficiency, and impaired liver function. Food banks, the primary response to food poverty on the ground, typically rely on community referral and distribution systems that involve health and social care professionals and local authority public health teams. The perspectives of these key stakeholders remain underexplored. This paper reports on a qualitative study of the health and wellbeing challenges of food poverty and food banking in London. An ethnographic investigation of food bank staff and users was carried out alongside a series of healthcare stakeholder interviews. A total of 42 participants were interviewed. A Critical Grounded Theory (CGT) analysis revealed that contemporary lived experiences of food poverty are embedded within and symptomatic of extreme marginalisation, which in turn impacts upon health. Specifically, food poverty was conceptualised by participants to: firstly, be a barrier to providing adequate care and nutrition for young children; secondly, be exacerbated by lack of access to adequate fresh food, food storage and cooking facilities; and thirdly, amplify existing health and social problems. Further investigation of the local government structures and professional roles that both rely upon and serve to further embed the food banking system is necessary in order to understand the politics of changing welfare landscapes
Systematic Techniques to Enhance rEtention in Randomised controlled trials: the STEER study protocol
Background
Non-retention of participants seriously affects the credibility of clinical trial results and significantly reduces the potential of a trial to influence clinical practice. Non-retention can be defined as instances where participants leave the study prematurely. Examples include withdrawal of consent and loss to follow-up and thus outcome data cannot be obtained. The majority of existing interventions targeting retention fail to describe any theoretical basis for the observed improvement, or lack of improvement. Moreover, most of these interventions lack involvement of participants in their conception and/or design, raising questions about their relevance and acceptability. Many of the causes of non-retention involve people performing a behaviour (e.g. not returning a questionnaire). Behaviour change is difficult, and the importance of a strong theoretical basis for interventions that aim to change behaviour is increasingly recognised. This research aims to develop and pilot theoretically informed, participant-centred, evidence-based behaviour change interventions to improve retention in trials.
Methods
This research will generate data through semi-structured interviews on stakeholders’ perspectives of the reasons for trial non-retention. It will identify perceived barriers and enablers to trial retention using the Theoretical Domains Framework. The intervention development work will involve identification of behaviour change techniques, using recognised methodology, and co-production of retention interventions through discussion groups with end-users. An evaluation of intervention acceptability and feasibility will be conducted in focus groups. Finally, a ready-to-use evaluation framework to deploy in Studies Within A Trial as well as an explanatory retention framework will be developed for identifying and tackling modifiable issues to improve trial retention.
Discussion
We believe this to be one of the first studies to apply a theoretical lens to the development of interventions to improve trial retention that have been informed by, and are embedded within, participants’ experiential accounts. By developing and identifying priority interventions this study will support efforts to reduce research waste
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