364 research outputs found
Statistical mechanics of voting
Decision procedures aggregating the preferences of multiple agents can
produce cycles and hence outcomes which have been described heuristically as
`chaotic'. We make this description precise by constructing an explicit
dynamical system from the agents' preferences and a voting rule. The dynamics
form a one dimensional statistical mechanics model; this suggests the use of
the topological entropy to quantify the complexity of the system. We formulate
natural political/social questions about the expected complexity of a voting
rule and degree of cohesion/diversity among agents in terms of random matrix
models---ensembles of statistical mechanics models---and compute quantitative
answers in some representative cases.Comment: 9 pages, plain TeX, 2 PostScript figures included with epsf.tex
(ignore the under/overfull \vbox error messages
The Banks set and the Uncovered Set in budget allocation problems
We examine how a society chooses to divide a given budget among various regions, projects or individuals. In particular, we characterize the Banks set and the Uncovered Set in such problems. We show that the two sets can be proper subsets of the set of all alternatives, and at times are very pointed in their predictions. This contrasts with well-known "chaos theorems," which suggest that majority voting does not lead to any meaningful predictions when the policy space is multidimensional
Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study
<p>Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.</p>
<p>The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.</p>
<p>Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.</p>
<p>Primary Objective β To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.</p>
<p>Secondary Objectives β To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.</p>
<p>Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p>
Genetic selection for fast growth generates bone architecture characterised by enhanced periosteal expansion and limited consolidation of the cortices but a diminution in the early responses to mechanical loading.
International audienceBone strength is, in part, dependent on a mechanical input that regulates the (re)modelling of skeletal elements to an appropriate size and architecture to resist fracture during habitual use. The rate of longitudinal bone growth in juveniles can also affect fracture incidence in adulthood, suggesting an influence of growth rate on later bone quality. We have compared the effects of fast and slow growth on bone strength and architecture in the tibiotarsi of embryonic and juvenile birds. The loading-related biochemical responses (intracellular G6PD activity and NO release) to mechanical load were also determined. Further, we have analysed the proliferation and differentiation characteristics of primary tibiotarsal osteoblasts from fast and slow-growing strains. We found that bones from chicks with divergent growth rates display equal resistance to applied loads, but weight-correction revealed that the bones from juvenile fast growth birds are weaker, with reduced stiffness and lower resistance to fracture. Primary osteoblasts from slow-growing juvenile birds proliferated more rapidly and had lower alkaline phosphatase activity. Bones from fast-growing embryonic chicks display rapid radial expansion and incomplete osteonal infilling but, importantly, lack mechanical responsiveness. These findings are further evidence that the ability to respond to mechanical inputs is crucial to adapt skeletal architecture to generate a functionally appropriate bone structure and that fast embryonic and juvenile growth rates may predispose bone to particular architectures with increased fragility in the adult. (C) 2009 Elsevier Inc. All rights reserved
Standardizing definitions and reporting guidelines for the infertility core outcome set : an international consensus development study
Acknowledgments We would like to thank the consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data or manuscript preparation. Siladitya Bhattacharya was supported by the University of Auckland Foundation Seelye Travelling Fellowship. B.W.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548) This article has not been externally peer reviewed. This article has been published simultaneously in Fertility and SterilityPeer reviewedPublisher PD
Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging
The value of in vivo preclinical diffusion MRI (dMRI) is substantial.
Small-animal dMRI has been used for methodological development and validation,
characterizing the biological basis of diffusion phenomena, and comparative
anatomy. Many of the influential works in this field were first performed in
small animals or ex vivo samples. The steps from animal setup and monitoring,
to acquisition, analysis, and interpretation are complex, with many decisions
that may ultimately affect what questions can be answered using the data. This
work aims to serve as a reference, presenting selected recommendations and
guidelines from the diffusion community, on best practices for preclinical dMRI
of in vivo animals. In each section, we also highlight areas for which no
guidelines exist (and why), and where future work should focus. We first
describe the value that small animal imaging adds to the field of dMRI,
followed by general considerations and foundational knowledge that must be
considered when designing experiments. We briefly describe differences in
animal species and disease models and discuss how they are appropriate for
different studies. We then give guidelines for in vivo acquisition protocols,
including decisions on hardware, animal preparation, imaging sequences and data
processing, including pre-processing, model-fitting, and tractography. Finally,
we provide an online resource which lists publicly available preclinical dMRI
datasets and software packages, to promote responsible and reproducible
research. An overarching goal herein is to enhance the rigor and
reproducibility of small animal dMRI acquisitions and analyses, and thereby
advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl
Intracellular SERS nanoprobes for distinction of different neuronal cell types.
Distinction between closely related and morphologically similar cells is difficult by conventional methods especially without labeling. Using nuclear-targeted gold nanoparticles (AuNPs) as intracellular probes we demonstrate the ability to distinguish between progenitor and differentiated cell types in a human neuroblastoma cell line using surface-enhanced Raman spectroscopy (SERS). SERS spectra from the whole cell area as well as only the nucleus were analyzed using principal component analysis that allowed unambiguous distinction of the different cell types. SERS spectra from the nuclear region showed the developments during cellular differentiation by identifying an increase in DNA/RNA ratio and proteins transcribed. Our approach using nuclear-targeted AuNPs and SERS imaging provides label-free and noninvasive characterization that can play a vital role in identifying cell types in biomedical stem cell research
Application of Direct Renin Inhibition to Chronic Kidney Disease
Chronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease.
Key clinical trials supporting the use of ACE inhibitors and ARBs in chronic kidney disease are discussed. Recent developments in our understanding of RAAS biology and the use of direct renin inhibition are reviewed in the context of their potential impact on the prevention and management of chronic kidney disease.
Despite the clinical success of ACE inhibitors and ARBs the rates of mortality and progression to renal failure remain high in these patient populations. ACE inhibitor or ARB monotherapy, in doses commonly used in clinical practice does not result in complete suppression of the RAAS. Aliskiren, a direct renin inhibitor, offers a novel approach to inhibit the RAAS in chronic kidney disease.
High dose ARB therapy or combination therapies with ACE inhibitors and ARBs have shown beneficial effects on surrogate markers of chronic kidney disease. Early data based on urinary protein excretion rates as a surrogate marker for renal function suggest a possibly novel role for aliskiren alone or in combination with ARBs in chronic kidney disease
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