Developing a health state classification system from NEWQOL for epilepsy using classical psychometric techniques and Rasch analysis: a technical report

Aims: Resource allocation amongst competing health care interventions is informed by evidence of both clinical- and cost-effectiveness. Cost-utility analysis is increasingly used to assess cost effectiveness through the use of Quality Adjusted Life Years (QALYs). This requires health state values. Generic measures of health related quality of life (HRQL) are usually used to produce these values, but there are concerns about their relevance and sensitivity in epilepsy. This study develops a health state classification system for epilepsy from the NEWQOL battery, a validated questionnaire measuring QoL in epilepsy. The classification system will be amenable to valuation for calculating QALYs. Methods: Factor and other psychometric analyses were undertaken to investigate the factor structure of the battery, and assess the validity and responsiveness of the items. These analyses were used alongside Rasch analysis to select the dimensions included in the classification system, and the items used to represent each domain. Analysis was carried out on a trial dataset of patients with epilepsy (n=1611). Rasch and factor analysis were performed on one half of the sample and validated on the remaining half. Dimensions and items were selected that performed well across all analyses. Results: The battery was found to demonstrate reliability and validity but responsiveness across time periods for many of the items was low. A six dimension classification system was developed: worry about seizures, depression, memory, cognition, stigmatism and control, each with four response levels. Conclusions: It is feasible to develop a health state classification system from a battery of instruments using a combination of classical psychometric, factor and Rasch analysis. This is the first condition-specific health state classification developed for epilepsy and the next stage will produce preference weights to enable the measure to be used in cost-utility analysis.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; epilepsy

Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair

GENERATION 2 CATIONIC CARBOSILANE DENDRIMERS HOLD GREAT PROMISE AS INTERNALIZING AGENTS FOR GENE THERAPY AS THEY PRESENT LOW TOXICITY AND RETAIN AND INTERNALIZE GENETIC MATERIAL AS OLIGONUCLEOTIDE OR SIRNA. IN THIS WORK WE CARRIED OUT A COMPLETE IN SILICO STRUCTURAL AND ENERGETICAL CHARACTERIZATION OF THE INTERACTIONS OF A SET OF 2G CARBOSILANE DENDRIMERS, SHOWING DIFFERENT AFFINITY TOWARDS TWO SINGLE STRAND OLIGONUCLEOTIDE (ODN) SEQUENCES IN VITRO. OUR SIMULATIONS PREDICT THAT THESE FOUR DENDRIMERS AND THE RELEVANT ODN COMPLEXES ARE CHARACTERIZED BY SIMILAR SIZE AND SHAPE, AND THAT THE MOLECULE-SPECIFIC ODN BINDING ABILITY CAN BE RATIONALIZED ONLY CONSIDERING A CRITICAL MOLECULAR DESIGN PARAMETER: THE NORMALIZED EFFECTIVE BINDING ENERGY \u394GBIND,EFF/NEFF I.E., THE PERFORMANCE OF EACH ACTIVE INDIVIDUAL DENDRIMER BRANCH DIRECTLY INVOLVED IN A BINDING INTERACTIO

Developing a health state classification system from NEWQOL for epilepsy using classical psychometric techniques and Rasch analysis: A technical report

Aims: Resource allocation amongst competing health care interventions is informed by evidence of both clinical- and cost-effectiveness. Cost-utility analysis is increasingly used to assess cost effectiveness through the use of Quality Adjusted Life Years (QALYs). This requires health state values. Generic measures of health related quality of life (HRQL) are usually used to produce these values, but there are concerns about their relevance and sensitivity in epilepsy. This study develops a health state classification system for epilepsy from the NEWQOL battery, a validated questionnaire measuring QoL in epilepsy. The classification system will be amenable to valuation for calculating QALYs. Methods: Factor and other psychometric analyses were undertaken to investigate the factor structure of the battery, and assess the validity and responsiveness of the items. These analyses were used alongside Rasch analysis to select the dimensions included in the classification system, and the items used to represent each domain. Analysis was carried out on a trial dataset of patients with epilepsy (n=1611). Rasch and factor analysis were performed on one half of the sample and validated on the remaining half. Dimensions and items were selected that performed well across all analyses. Results: The battery was found to demonstrate reliability and validity but responsiveness across time periods for many of the items was low. A six dimension classification system was developed: worry about seizures, depression, memory, cognition, stigmatism and control, each with four response levels. Conclusions: It is feasible to develop a health state classification system from a battery of instruments using a combination of classical psychometric, factor and Rasch analysis. This is the first condition-specific health state classification developed for epilepsy and the next stage will produce preference weights to enable the measure to be used in cost-utility analysis

Pteridine-2,4-diamine derivatives as radical scavengers and inhibitors of lipoxygenase that can possess anti-inflammatory properties

BACKGROUND: Reactive oxygen species are associated with inflammation implicated in cancer, atherosclerosis and autoimmune diseases. The complex nature of inflammation and of oxidative stress suggests that dual-target agents may be effective in combating diseases involving reactive oxygen species. RESULTS: A novel series of N-substituted 2,4-diaminopteridines has been synthesized and evaluated as antioxidants in several assays. Many exhibited potent lipid antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50 values extending down to 100 nM for both targets. Several pteridine derivatives showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f) at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%). CONCLUSION: The 2,4-diaminopteridine core represents a new scaffold for lipoxygenase inhibition as well as sustaining anti-inflammatory properties

Qualitative study of paramedics' experiences of managing seizures: A national perspective from England

Objectives: The UK ambulance service is expected to now manage more patients in the community and avoid unnecessary transportations to hospital emergency departments (ED). Most people it attends who have experienced seizures have established epilepsy, have experienced uncomplicated seizures and so do not require the full facilities of an ED. Despite this, most are transported there. To understand why, we explored paramedics experiences of managing seizures. Design and setting: Semistructured interviews were conducted with a purposive sample of paramedics from the English ambulance service. Interviews were transcribed and thematically analysed. Participants: A diverse sample of 19 professionals was recruited from 5 different ambulance NHS trusts and the College of Paramedics. Results: Participants confirmed how most seizure patients attended to do not clinically require an ED. They explained, however, that a number of factors influence their care decisions and create a momentum for these patients to still be taken. Of particular importance was the lack of access paramedics have to background medical information on patients. This, and the limited seizure training paramedics receive, meant paramedics often cannot interpret with confidence the normality of a seizure presentation and so transport patients out of precaution. The restricted time paramedics are expected to spend on scene due to the way the ambulance services performance is measured and that are few alternative care pathways which can be used for seizure patients also made conveyance likely. Conclusions: Paramedics are working within a system that does not currently facilitate nonconveyance of seizure patients. Organisational, structural, professional and educational factors impact care decisions and means transportation to ED remains the default option. Improving paramedics access to medical histories, their seizure management training and developing performance measures for the service that incentivise care that is cost-effective for all of the health service might reduce unnecessary conveyances to ED

Qualidade de silagens de bagaço úmido de laranja e cama de frango e desempenho de novilhos Canchim.

A qualidade de silagens de bagaço de laranja e cama-de-frango com diferentes proporções (80:20; 60:40; 40:60 e 20:80) e de silagem pura de cama-de-frango com diferentes teores de matéria seca, obtidos pela utilização de diferentes proporções de água e cama-de-frango (0:100; 15:85; 30:70 e 45:55) foram avaliadas em silos de laboratório. Uma silagem com 45:55 de cama-de-frango e bagaço de laranja foi utilizada para teste de ganho de peso com animais Canchim. Houve incremento (P<0,05) na porcentagem de MS, PB, pH, FDN, , cinzas, amônia, Ca e P com o aumento da proporções de cama-de-frango em relação ao bagaço de laranja. A silagem com 15:85 apresentou maior teor de PB e menor teor de amônia que as silagens com 30:70 e 45:55. A dieta com silagem de bagaço de laranja e cama-de-frango, cana-de-açúcar e concentrado (44:36:20), na base seca, permitiu consumo adequado para ganho de peso de 1,39 kg por dia

Electronic submission and the movement towards a paperless law office in a modern university

The Government’s target of 50% of all under 30 year olds studying at higher education institutions by 2010, coupled with the National Committee Inquiry into Higher Education’ (1997) concluding that further expansion of higher education could not be afforded under the existing funding arrangements, may have serious ramifications for higher education in the UK. Alongside this increase in numbers, students are increasingly seen as educational consumers with increased choice in a demand-led market which universities must recognise. To compete in this academic environment these institutions are having to be ever more consumer aware in the services they offer and are having to increase choice to attract customers from rival enterprises. Information technology is playing an increasing role in the learning experience as noted by institutional commentators such as the Higher Education Funding Council for England, the Joint Information Systems Committee, the Electronic Books ON-screen Interface group and Lord Dearing’s Report. Technology’s use is further evidenced through institutions’ employment of the internet, e-mail and web-based learning to harness the power of this medium. This paper focuses on the concept of commercialism in the university sector and how a movement to a paperless office may be one way in which a university could gain an early competitive advantage over its rivals. The paper takes a student perspective to demonstrate whether students would wish to move towards electronic methods of submission of assessed work and considers the current problems that are encountered in physical submission of documents. This is the first paper in an on-going research project investigating the benefits and viability of a paperless law office, and the results demonstrate both that the students desire more flexibility in submission of university work and that their acceptance may be the easy first step on the road to the paperless law school

Landscape of stimulation-responsive chromatin across diverse human immune cells.

A hallmark of the immune system is the interplay among specialized cell types transitioning between resting and stimulated states. The gene regulatory landscape of this dynamic system has not been fully characterized in human cells. Here we collected assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing data under resting and stimulated conditions for up to 32 immune cell populations. Stimulation caused widespread chromatin remodeling, including response elements shared between stimulated B and T cells. Furthermore, several autoimmune traits showed significant heritability in stimulation-responsive elements from distinct cell types, highlighting the importance of these cell states in autoimmunity. Allele-specific read mapping identified variants that alter chromatin accessibility in particular conditions, allowing us to observe evidence of function for a candidate causal variant that is undetected by existing large-scale studies in resting cells. Our results provide a resource of chromatin dynamics and highlight the need to characterize the effects of genetic variation in stimulated cells

Observing the Sun with the Atacama Large Millimeter-submillimeter Array (ALMA): Fast-Scan Single-Dish Mapping

The Atacama Large Millimeter-submillimeter Array (ALMA) radio telescope has commenced science observations of the Sun starting in late 2016. Since the Sun is much larger than the field of view of individual ALMA dishes, the ALMA interferometer is unable to measure the background level of solar emission when observing the solar disk. The absolute temperature scale is a critical measurement for much of ALMA solar science, including the understanding of energy transfer through the solar atmosphere, the properties of prominences, and the study of shock heating in the chromosphere. In order to provide an absolute temperature scale, ALMA solar observing will take advantage of the remarkable fast-scanning capabilities of the ALMA 12m dishes to make single-dish maps of the full Sun. This article reports on the results of an extensive commissioning effort to optimize the mapping procedure, and it describes the nature of the resulting data. Amplitude calibration is discussed in detail: a path that utilizes the two loads in the ALMA calibration system as well as sky measurements is described and applied to commissioning data. Inspection of a large number of single-dish datasets shows significant variation in the resulting temperatures, and based on the temperature distributions we derive quiet-Sun values at disk center of 7300 K at lambda=3 mm and 5900 K at lambda=1.3 mm. These values have statistical uncertainties of order 100 K, but systematic uncertainties in the temperature scale that may be significantly larger. Example images are presented from two periods with very different levels of solar activity. At a resolution of order 25 arcsec, the 1.3 mm wavelength images show temperatures on the disk that vary over about a 2000 K range.Comment: Solar Physics, accepted: 24 pages, 13 figure