Polarization of coalitions in an agent-based model of political discourse

Political discourse is the verbal interaction between political actors in a policy domain. This article explains the formation of polarized advocacy or discourse coalitions in this complex phenomenon by presenting a dynamic, stochastic, and discrete agent-based model based on graph theory and local optimization. In a series of thought experiments, actors compute their utility of contributing a specific statement to the discourse by following ideological criteria, preferential attachment, agenda-setting strategies, governmental coherence, or other mechanisms. The evolving macro-level discourse is represented as a dynamic network and evaluated against arguments from the literature on the policy process. A simple combination of four theoretical mechanisms is already able to produce artificial policy debates with theoretically plausible properties. Any sufficiently realistic configuration must entail innovative and path-dependent elements as well as a blend of exogenous preferences and endogenous opinion formation mechanisms

A national survey of services for the prevention and management of falls in the UK

Background: The National Health Service (NHS) was tasked in 2001 with developing service provision to prevent falls in older people. We carried out a national survey to provide a description of health and social care funded UK fallers services, and to benchmark progress against current practice guidelines. Methods: Cascade approach to sampling, followed by telephone survey with senior member of the fall service. Characteristics of the service were assessed using an internationally agreed taxonomy. Reported service provision was compared against benchmarks set by the National Institute for Health and Clinical Excellence (NICE). Results: We identified 303 clinics across the UK. 231 (76%) were willing to participate. The majority of services were based in acute or community hospitals, with only a few in primary care or emergency departments. Access to services was, in the majority of cases, by health professional referral. Most services undertook a multi-factorial assessment. The content and quality of these assessments varied substantially. Services varied extensively in the way that interventions were delivered, and particular concern is raised about interventions for vision, home hazard modification, medication review and bone health. Conclusion: The most common type of service provision was a multi-factorial assessment and intervention. There were a wide range of service models, but for a substantial number of services, delivery appears to fall below recommended NICE guidance

Kerr-Newman Black Hole Thermodynamical State Space: Blockwise Coordinates

A coordinate system that blockwise-simplifies the Kerr-Newman black hole's thermodynamical state space Ruppeiner metric geometry is constructed, with discussion of the limiting cases corresponding to simpler black holes. It is deduced that one of the three conformal Killing vectors of the Reissner-Nordstrom and Kerr cases (whose thermodynamical state space metrics are 2 by 2 and conformally flat) survives generalization to the Kerr-Newman case's 3 by 3 thermodynamical state space metric.Comment: 4 pages incl 2 figs. Accepted by Gen. Rel. Grav. Replaced with Accepted version (minor corrections

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Volumetry of the dominant intraprostatic tumour lesion: intersequence and interobserver differences on multiparametric MRI.

Objective To establish the interobserver reproducibility of tumour volumetry on individual multiparametric (mp) prostate MRI sequences, validate measurements with histology and determine whether functional to morphological volume ratios reflect Gleason score.Methods 41 males with prostate cancer treated with prostatectomy (Cohort 1) or radical radiotherapy (Cohort 2), who had pre-treatment mpMRI [T2 weighted (T2W) MRI, diffusion-weighted (DW)-MRI and dynamic contrast-enhanced (DCE)-MRI], were studied retrospectively. Dominant intraprostatic lesions (DIPLs) were manually delineated on each sequence and volumes were compared between observers (n = 40 analyzable) and with radical prostatectomy (n = 20). Volume ratios of DW-MRI and DCE-MRI to T2W MRI were documented and compared between Gleason grade 3 + 3, 3 + 4 and 4 + 3 or greater categories.Results Limits of agreement of DIPL volumes between observers were: T2W MRI 0.9, -1.1 cm3, DW-MRI 1.3, -1.7 cm3 and DCE-MRI 0.74, -0.89 cm3. In Cohort 1, T2W volumes overestimated fixed specimen histological volumes (+33% Observer 1, +16% Observer 2); DW- and DCE-MRI underestimated histological volume, the latter markedly so (-32% Observer 1, -79% Observer 2). Differences between T2W, DW- and DCE-MRI volumes were significant (p -8). The ratio of DW-MRI volume (73.9 ± 18.1% Observer 1, 72.5 ± 21.9% Observer 2) and DCE-MRI volume (42.6 ± 24.6% Observer 1, 34.3 ± 24.9% Observer 2) to T2W volume was significantly different (p -8), but these volume ratios did not differ between the Gleason grades.Conclusion The low variability of the DIPL volume on T2W MRI between Observers and agreement with histology indicates its suitability for delineation of gross tumour volume for radiotherapy planning. The volume of cellular tumour represented by DW-MRI is greater than the vascular (DCE) abnormality; ratios of both to T2W volume are independent of Gleason score. Advances in knowledge: (1) Manual volume measurement of tumour is reproducible within 1 cm3 between observers on all sequences, confirming suitability across observers for radiotherapy planning. (2) Volumes derived on T2W MRI most accurately represent in vivo lesion volumes. (3) The proportion of cellular (DW-MRI) or vascular (DCE-MRI) volume to morphological (T2W MRI) volume is not affected by Gleason score

Two-dimensional Dirac fermions in a topological insulator: transport in the quantum limit

Pulsed magnetic fields of up to 55T are used to investigate the transport properties of the topological insulator Bi_2Se_3 in the extreme quantum limit. For samples with a bulk carrier density of n = 2.9\times10^16cm^-3, the lowest Landau level of the bulk 3D Fermi surface is reached by a field of 4T. For fields well beyond this limit, Shubnikov-de Haas oscillations arising from quantization of the 2D surface state are observed, with the \nu =1 Landau level attained by a field of 35T. These measurements reveal the presence of additional oscillations which occur at fields corresponding to simple rational fractions of the integer Landau indices.Comment: 5 pages, 4 figure

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (≥ 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified

Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal

OBJECTIVE: To examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is safe and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram, can increase HIV transcription in people with HIV (PWH) on antiretroviral therapy (ART). Together these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated (CA) unspliced (US) RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA and plasma concentrations of ART, vorinostat and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4- and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8-37 (peak 81 copies/mL) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSIONS: The combination of prolonged high dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal