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

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

The phases of the Moon : modelling crystallisation of the lunar magma ocean through equilibrium thermodynamics

Funding: TEJ acknowledges support from the State Key Laboratory for Geological Processes and Mineral Resources, China University of Geosciences, Wuhan (Open Fund GPMR201903 ). We thank J. B. Balta and T. Prissel for their challenging reviews that led to significant improvements in the final version.Despite some 50 years of intense research on samples returned from the Apollo missions and lunar meteorites, along with remote-sensing and Earth-based observations, many questions regarding the formation and evolution of the Moon persist. These include the detailed compositional and density structure of the lunar mantle and the source and petrogenesis of the diverse suite of extrusive and intrusive igneous rocks. There is broad agreement that the primary internal structure of the Moon reflects crystallisation of a lunar magma ocean (LMO), and that an inverted density gradient within the mantle cumulates led to some reorganisation of layers by partial convective overturn. Experimental studies have provided invaluable constraints on crystallisation of the LMO, but are limited by the relatively small number of experiments that can practically be undertaken. Here we use recently-developed thermodynamic models for minerals and melt in the K2O–Na2O–CaO–FeO–MgO–Al2O3–SiO2–TiO2–Cr2O3 system to model crystallisation of a full-moon LMO based on two existing end-member bulk compositions—Taylor Whole-Moon (TWM), and Lunar Primitive Upper Mantle, LPUM—on which many experimental studies have been based. We follow several recent studies in considering equilibrium crystallisation of the first 50 vol.% and fractional crystallisation thereafter. Our results match well with experimental studies, and provide detailed constraints on the major oxide composition, mineralogy and density structure based on the two starting compositions that, while exhibiting some similarities, show important differences. The more fertile TWM composition contains significant quantities of garnet in the deep mantle, whereas the LPUM composition has none. By contrast, prior to any gravitational overturn, the uppermost mantle cumulates for TWM are strongly silica-undersaturated and contain abundant aluminous spinel, whereas those for LPUM are silica-saturated. For both starting compositions, with the exception of TiO2 and Na2O, our modelled compositions of the final dregs of fractionated melt show a reasonable match with existing estimates on the composition of urKREEP. Modelled partial melts of the upper-mantle cumulates at low to moderate melt fractions have major oxide compositions that match well with low- and intermediate-Ti lunar basalts. The correspondence is particularly good for picritic (green) glasses that likely represent melts derived from deeper levels within the upper mantle. The wide spread in TiO2 concentrations in lunar basalts and basaltic glasses is consistent with density-driven reorganisation involving ilmenite. Our simulations provide thermodynamically-robust estimates of the compositional, mineralogical and density structure of the lunar interior that are unprecedented in their detail, and which provide the foundation for several lines of future research addressing the origin and secular evolution of the Moon.PostprintPeer reviewe

Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action

It is becoming increasingly clear that plants, ranging from across the plant kingdom produce anionic host defence peptides (AHDPs) with potent activity against a wide variety of human cancers cells. In general, this activity involves membrane partitioning by AHDPs, which leads to membranolysis and / or internalization to attack intracellular targets such as DNA. Several models have been proposed to describe these events including: the toroidal pore and Shai-Matsuzaki-Huang mechanisms but, in general, the mechanisms underpinning the membrane interactions and anticancer activity of these peptides are poorly understood. Plant AHDPs with anticancer activity can be conveniently discussed with reference to two groups: cyclotides, which possess cyclic molecules stabilized by cysteine knot motifs, and other ADHPs that adopt extended and α-helical conformations. Here, we review research into the anticancer action of these two groups of peptides along with current understanding of the mechanisms underpinning this action

Novel Insights into Selection for Antibiotic Resistance in Complex Microbial Communities

This is the final version of the article. Available from American Society for Microbiology via the DOI in this record.Recent research has demonstrated that selection for antibiotic resistance occurs at very low antibiotic concentrations in single-species experiments, but the relevance of these findings when species are embedded in complex microbial communities is unclear. We show that the strength of selection for naturally occurring resistance alleles in a complex community remains constant from low subinhibitory to above clinically relevant concentrations. Selection increases with antibiotic concentration before reaching a plateau where selection remains constant over a 2-order-magnitude concentration range. This is likely to be due to cross protection of the susceptible bacteria in the community following rapid extracellular antibiotic degradation by the resistant population, shown experimentally through a combination of chemical quantification and bacterial growth experiments. Metagenome and 16S rRNA analyses of sewage-derived bacterial communities evolved under cefotaxime exposure show preferential enrichment for blaCTX-M genes over all other beta-lactamase genes, as well as positive selection and co-selection for antibiotic resistant, opportunistic pathogens. These findings have far-reaching implications for our understanding of the evolution of antibiotic resistance, by challenging the long-standing assumption that selection occurs in a dose-dependent manner.Aimee K. Murray was supported by a BBSRC/AZ CASE Studentship, BB/L502509/1. Lihong Zhang was supported by Natural Environment Research Council grant NE/ M011259/1. Chemical quantification was performed at the University of Exeter Streatham Campus by Maciek Trnzadel and Malcolm Hetheridge, cofunded by Astra Zeneca Global SHE and the University of Exeter

New monitoring confirms regular breeding of the Mediterranean monk seal in Northern Cyprus

The Endangered Mediterranean monk seal Monachus monachus is one of the most threatened marine mammals. Across Cyprus, suitable habitat and presence of monk seals is well documented and, recently, camera-trap surveys in Southern Cyprus found there to be pupping. We present results of the first camera-trap surveys in Northern Cyprus spanning the pupping period. Four adult/subadults and three pups were identified in three of eight caves monitored with camera traps. One site on the north-west of the island supported at least three adult/subadult seals and pupping occurred there in 3 consecutive years. The breeding and resting sites identified require urgent conservation to manage threats of disturbance, coastal development and fisheries bycatch. To determine the size of this population, a long-term survey with greater and more continuous coverage is required

The importance of passive integrated transponder (PIT) tags for measuring life-history traits of sea turtles

Capture-mark-recapture studies rely on the identification of individuals through time, using markers or tags, which are assumed to be retained. This assumption, however, may be violated, having implications for population models. In sea turtles, individual identification is typically based on external flipper tags, which can be combined with internal passive integrated transponder (PIT) tags. Despite the extensive use of flipper tags, few studies have modelled tag loss using continuous functions. Using a 26-year dataset for sympatrically nesting green (Chelonia mydas) and loggerhead (Caretta caretta) turtles, this study aims to assess how PIT tag use increases the accuracy of estimates of life-history traits. The addition of PIT tags improved female identification: between 2000 and 2017, 53% of green turtles and 29% of loggerhead turtles were identified from PIT tags alone. We found flipper and PIT tag losses were best described by decreasing logistic curves with lower asymptotes. Excluding PIT tags from our dataset led to underestimation of flipper tag loss, reproductive periodicity, reproductive longevity and annual survival, and overestimation of female abundance and recruitment for both species. This shows the importance of PIT tags in improving the accuracy of estimates of life-history traits. Thus, estimates where tag loss has not been corrected for should be interpreted with caution and could bias IUCN Red List assessments. As such, long-term population monitoring programmes should aim to estimate tag loss and assess the impact of loss on life-history estimates, to provide robust estimates without which population models and stock assessments cannot be derived accurately

Meanings of epilepsy in its sociocultural context and implications for stigma: Findings from ethnographic studies in local communities in China and Vietnam

We investigated beliefs about the causes, course, and treatment of epilepsy and its impact on quality of life (QOL) in key target groups, using “mini-ethnographies” involving 141 in-depth interviews and 12 focus groups in China, and 84 in-depth interviews and 16 focus groups in Vietnam. Data were analyzed thematically, using a qualitative data analysis package. In both countries, beliefs about causes and triggers of epilepsy and seizures were a complex interweaving of Western, traditional, and folk medicine concepts. Epilepsy was understood to be chronic, not curable, but controllable, and was seen as enormously socially disruptive, with wide-ranging impact on QOL. Our findings suggest a more “embodied” and benign set of theories about epilepsy than in some other cultural contexts; nonetheless, people with epilepsy are still seen as having low social value and face social rejection. By exploring meanings attached to epilepsy in these two cultural contexts, we have clarified reasons behind previously documented negative attitudes and foci for future intervention studies

Impacts of local human activities on the Antarctic environment

We review the scientific literature, especially from the past decade, on the impacts of human activities on the Antarctic environment. A range of impacts has been identified at a variety of spatial and temporal scales. Chemical contamination and sewage disposal on the continent have been found to be long-lived. Contemporary sewage management practices at many coastal stations are insufficient to prevent local contamination but no introduction of non-indigenous organisms through this route has yet been demonstrated. Human activities, particularly construction and transport, have led to disturbances of flora and fauna. A small number of non-indigenous plant and animal species has become established, mostly on the northern Antarctic Peninsula and southern archipelagos of the Scotia Arc. There is little indication of recovery of overexploited fish stocks, and ramifications of fishing activity oil bycatch species and the ecosystem could also be far-reaching. The Antarctic Treaty System and its instruments, in particular the Convention for the Conservation of Antarctic Marine Living Resources and the Environmental Protocol, provide a framework within which management of human activities take place. In the face of the continuing expansion of human activities in Antarctica, a more effective implementation of a wide range of measures is essential, in order to ensure comprehensive protection of the Antarctic environment, including its intrinsic, wilderness and scientific values which remains a fundamental principle of the Antarctic Treaty System. These measures include effective environmental impact assessments, long-term monitoring, mitigation measures for non-indigenous species, ecosystem-based management of living resources, and increased regulation of National Antarctic Programmes and tourism activities

It's the product not the polymer: Rethinking plastic pollution

Mismanaged plastic waste poses a complex threat to the environments that it contaminates, generating considerable concern from academia, industry, politicians, and the general public. This concern has driven global action that presents a unique opportunity for widespread environmental engagement beyond the immediate problem of the persistence of plastic in the environment. But for such an opportunity to be realized, it is vital that the realities of plastic waste are not misrepresented or exaggerated. Hotspots of plastic pollution, which are often international in their source, present complex environmental problems in certain parts of the world. Here we argue, however, that the current discourse on plastic waste overshadows greater threats to the environment and society at a global scale. Antiplastic sentiments have been exploited by politicians and industry, where reducing consumers' plastic footprints are often confused by the seldom‐challenged veil of environmental consumerism, or “greenwashing.” Plastic is integral to much of modern day life, and regularly represents the greener facilitator of society's consumption. We conclude that it is the product, not the polymer that is driving the issue of plastic waste. Contemporary consumption and disposal practices are the root of much of the anthropogenic waste in the environment, plastic, or not. Effective environmental action to minimize plastic in the environment should be motivated by changes in consumption practices, policies, and product design, and should be informed by objective science and legislation