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Background:Positron emission tomography (PET) and single photon emission computed tomography (SPECT) brain imaging are widely used as diagnostic tools for suspected dementia but no studies have directly compared participant views of the two procedures. We used a range of methods to explore preferences for PET and SPECT.Methods:Patients and controls (and accompanying carers) completed questionnaires immediately after undergoing PET and SPECT brain scans. Pulse rate data were collected during each scan. Scan attributes were prioritized using a card sorting exercise; carers and controls additionally answered willingness to pay (WTP) questions.Results:Few differences were found either between the scans or groups of participants, although carers marginally preferred SPECT. Diagnostic accuracy was prioritized over other scan characteristics. Mean heart rate during both scans was lower than baseline heart rate measured at home (p < 0.001).Conclusion:Most participants viewed PET and SPECT scans as roughly equivalent and did not have a preference for either scan. Carer preference for SPECT is likely to reflect their desire to be with the patient (routine practice for SPECT but not for PET), suggesting that they should be able to accompany vulnerable patients throughout imaging procedures wherever possible. Pulse rate data indicated that brain imaging was no more stressful than a home visit (HV) from a researcher. The data do not support the anecdotal view that PET is a more burdensome procedure and the use of PET or SPECT scans in dementia should be based on diagnostic accuracy of the technique.

Background Middle income countries are facing an epidemic of non-communicable diseases, especially coronary heart disease (CHD). We used a validated CHD mortality model (IMPACT) to explain recent trends in Tunisia, Syria, the occupied Palestinian territory (oPt) and Turkey. Methods Data on populations, mortality, patient numbers, treatments and risk factor trends from national and local surveys in each country were collated over two time points (1995-97; 2006-09); integrated and analysed using the IMPACT model. Results Risk factor trends: Smoking prevalence was high in men, persisting in Syria but decreasing in Tunisia, oPt and Turkey. BMI rose by 1-2 kg/m2 and diabetes prevalence increased by 40%-50%. Mean systolic blood pressure and cholesterol levels increased in Tunisia and Syria. Mortality trends: Age-standardised CHD mortality rates rose by 20% in Tunisia and 62% in Syria. Much of this increase (79% and 72% respectively) was attributed to adverse trends in major risk factors, occurring despite some improvements in treatment uptake. CHD mortality rates fell by 17% in oPt and by 25% in Turkey, with risk factor changes accounting for around 46% and 30% of this reduction respectively. Increased uptake of community treatments (drug treatments for chronic angina, heart failure, hypertension and secondary prevention after a cardiac event) accounted for most of the remainder. Discussion CHD death rates are rising in Tunisia and Syria, whilst oPt and Turkey demonstrate clear falls, reflecting improvements in major risk factors with contributions from medical treatments. However, smoking prevalence remains very high in men; obesity and diabetes levels are rising dramatically. The MedCHAMPS project and data collection were funded by EC FP7 grant no. 223705 . JC and SC are supported by the UK Higher Education Funding Council . MOF was partly funded by the European Union and the UK Medical Research Council ( NPR3, Project 45 ). This study was funded by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 223075 - the MedCHAMPS project. MOF was also supported by the UK MRC . Scopus

[Extract] In this chapter, we introduce readers to key concepts of health economics, with particular relevance to the role of economic evaluation in population health. The material here was derived from a contemporary series of blogs on the economics of population health (www.gcph.co.uk/latest/blogs) with the aim of facilitating fresh thinking on key matters of importance in the economics of population health.

A new calculation of rate coefficients for electron collisional excitation of Fe XII is presented and compared to earlier calculations. Significant differences are found with all earlier work due to the inclusion of resonance processes that have not previously been considered and to the use of the intermediate coupling frame transformation method. The resulting dataset of collision strengths is shown to resolve many of the outstanding discrepancies between theory and solar observations. In particular, density sensitive line ratios in Fe XII now indicate electron densities close to those derived from other ions of comparable ionization potential.

Collision strengths for electron induced transitions in the beryllium-like ion Fe+22 are calculated using the intermediate coupling frame transformation (ICFT) version of the R-matrix programs. Our target has 98 fine structure states 1 s(2) nl n'l' S LJ corresponding to n = 2 and n' = 2, 3, 4. The present calculation is for electron impact energies in the range 3.15 to 380 Ry. When T exceeds about ten million degrees one needs to take account of contributions to the thermally averaged collision strength Y coming from electrons with energies in excess of 380 Ry. We discuss a way of allowing for these contributions. Values of Y for all the transitions between the ground state and the excited states 1s(2) 2l n l n'l' S' L' J', with n' = 2, 3,4 are tabulated as a function of log T. The temperature range 6.3 less than or equal to log T less than or equal to 8.1 is centred on log T = 7.1 which is approximately where Fe+22 has maximum abundance in ionization equilibrium. To the best of our knowledge these are the first R-matrix calculations for Fe+22 for excitations to the n = 3, 4 levels. Good agreement with previous distored-wave calculations is found. However, the resonance contributions have an important effect on the effective collision strengths and in turn on the level populations.

β-Alanine derivative 2 (IC 50 =16 nM) and related compounds were found to be potent MC4R agonists.

Objective To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. Design Cultured ovarian cells. Setting Academic research environment. Patient(s) Women undergoing bilateral salpingoophorectomy for benign gynecological disease. Main outcome measure(s) Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. Result(s) The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E 2 was seen (range 0%–30%). Metformin dose-dependently inhibited gonadotrophin and insulin -stimulated P and E 2 production (range 25%–50%). In theca, metformin inhibited A production (0%–40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude. Conclusion(s) These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).

The ovarian insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system operates to permit maximal stimulation of steroidogenesis in the dominant follicle. In atretic follicles, the predominant IGFBPs are IGFBP-2 and IGFBP-4, which appear to be selectively cleaved in healthy follicles. We have recently demonstrated potent inhibition by IGFBP-4 of both theca and granulosa cell steroid production. The degree to which the inhibition occurred suggested that it was greater than might be expected by sequestration of IGF alone. Our study was designed to test this idea. Granulosa cells were harvested from follicles dissected intact from patients undergoing total abdominal hysterectomy and bilateral salpingoophorectomy. Granulosa cells were incubated with or without gonadotropins and IGFBP-4 in the presence or absence of either the IGF type I receptor blocker αIR3 or excess IGFBP-3 to remove the effects of endogenous IGF action. Steroid accumulation in the medium was assessed. IGFBP-4 continued to exert potent inhibitory effects when the action of endogenous IGF was removed from the system, demonstrating that its actions are independent of IGF binding. There was no effect on cell metabolism, and the effects on steroidogenesis were reversible after IGFBP-4 removal from the culture medium. No similar effects were seen with IGFBP-2. These reasults are the first evidence of IGF-independent IGFBP-4 actions and the first evidence of IGF-independent actions of any IGFBPs in the ovary.

Objective To determine the optimal weight-to-height ratio to achieve maturity of the reproductive organs when visualized by pelvic ultrasound in adolescent girls with anorexia nervosa. To examine the distribution of weight-to-height ratios in the group of adolescents in whom pelvic maturity was attained. Methods Adolescent girls with anorexia nervosa received serial transabdominal pelvic ultrasound scans as they regained weight. A record of their weight-to-height ratio had been noted on each occasion. The scans were defined as mature or immature using strict criteria. Results There was a wide range of weight-to-height ratios in both the mature and immature groups of patients with a considerable overlap between the groups. However, 88% of the sample required a weight-to-height ratio of 100% (body mass index [BMI] 20) to achieve reproductive maturity. Conclusion Previous target weights have been too low to ensure reproductive maturity. The resulting hypoestrogenic state increases the risk of future osteoporosis. Pelvic ultrasound is the safest and most reliable method for determining ovarian and uterine maturity in adolescent girls with anorexia nervosa. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 32: 319–325, 2002.

REDX05358 has been identified as a novel, highly selective and potent next generation pan RAF inhibitor with improved therapeutic potential and predicted safety profile. Aberrant signalling via the MAPK pathway is commonly seen in cancer. RAF inhibitors such as Dabrafenib and Vemurafenib have been approved for the treatment of unresectable and metastatic BRAF mutant melanoma, but these agents lack efficacy in BRAF mutant colorectal cancer (CRC), partly because of EGFR-mediated feedback reactivation of the MAPK pathway via CRAF. Furthermore, RAF inhibitor treatment of RAS-mutant, BRAF wildtype melanomas has been associated with other skin cancers, such as cutaneous squamous cell carcinoma due to MAPK pathway paradoxical activation mediated by CRAF. There is therefore a clinical need for novel agents targeting the MAPK pathway that do not have these undesirable properties. Here we present, REDX05358 that demonstrates subnanomolar binding affinity for BRAF and CRAF with high selectivity profile against a panel of 468 kinases that exhibits negligible paradoxical activation due to inhibition of both RAF monomers and dimers. As a result, REDX05358 not only inhibits MAPK signalling in BRAF V600E mutant tumor cells, but also in those harbouring NRAS and KRAS mutations. Furthermore, REDX05358 does not induce feedback reactivation of the pathway through its ability to sustain inhibition of MAPK signalling in CRC cell lines. Correspondingly, profiling of REDX05358 in a panel of CRC, melanoma and NSCLC cell lines shows it has potent anti-proliferative activity in cell lines harbouring BRAF or RAS mutations. REDX05358 is an orally bioavailable, well tolerated small molecule that has demonstrated in vivo efficacy in BRAF V600E CRC xenograft model. In contrast, first generation inhibitors such as Vemarafenib and Dabrafanib have been reported to be ineffective in this genetic background in CRC cell lines and patients. Thus, we have developed a pan RAF inhibitor with unique pharmacological properties enabling it to have utility in treating BRAF and RAS mutant cancers Citation Format: Helen Mason, Simon Scrace, Richard Testar, Julie Rainard, Fatima Talab, Ryaka Poonawala, Philippa Smith, Harriet Brooke, Sarah Frith, Jonathan Ahmet, Jonathan Hall, David Sorrell, Jon Moore, Caroline Phillips, Dennis France, Matilda Bingham, Richard Armer. Development of REDX05358, a novel highly selective and potent pan RAF inhibitor and a potential therapeutic for BRAF and RAS mutant tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5160. doi:10.1158/1538-7445.AM2017-5160

What is animation? This article defines different types of animation and explores its therapeutic potential.

The valuation of health in monetary terms can be estimated by observing real choices or by eliciting willingness to pay (WTP) through presentation of hypothetical choices to respondents (contingent valuation). Contingent valuation is commonly used in other areas of the public sector and its use is growing in health. In this article, the authors outline the rationale for such monetary valuation via WTP measurement before going on to discuss challenges associated with different approaches and provide examples from some recent case studies of how such monetary measurement has been achieved.

The key drivers of population health lie outside the health sector. However, decision makers outside the health sector are primarily interested in delivering sector specific outputs other than health. Economic approaches to priority setting can help align sectors to consider the intersectoral impacts of decisions within an integrated societal framework. First, economic evaluation can explicitly identify and measure all impacts – including health – and value them as inputs into overall social welfare. Second, priority setting tools such as program budgeting marginal analysis and multi-criteria decision analysis can then be used to help translate evidence into policy, where the full consequences of decisions are considered and the overall aim is to improve social welfare.

We present multi-instrument observations of AR 8048, made between June 3 and June 5 1997 as part of SoHO JOP033. This active region (AR) has a sigmoid-like global shape and undergoes transient brightenings through which the stored energy is released.Using a magneto-hydrostatic model, we compute coronal magnetic field. The large-scale magnetic lines confirm the sigmoidal characteristics of the AR. The field lines most closely matching the hotter SoHO/CDS loops extend along the quasi-separatrix-Iayers (QSLs) of the coronal field. Transition region (TR) brightenings observed with SoHO/CDS can be associated with both QSL intersections with the photosphere, and places where separatrices corresponding to bald patches (BPs, sites where field lines are tangent to the photosphere) lie at the photospheric plane. There are suggestions that the element abundances measured in the TR may depend on the type of topological structure present. TR brightenings associated with QSLs have coronal abundances, while those associated with BP separatrices have abundances closer to photospheric values.

The mechanism of the increase in the number of follicles in polycystic ovaries (PCO) is still not understood, but most data indicate that folliculogenesis is abnormal at all stages. This increase is probably due to prolonged follicle growth in both ovulatory (ov) and anovulatory PCO (anovPCO) rather than over-recruitment from the primordial stage. There appear to be fewer follicles in ovPCO than in anovPCO and this may be due to slow growth combined with arrested development in the anovPCO, preventing the normal process of atresia. This idea is supported by data indicating that the preponderance of structures in anovPCO are functional follicles rather than atretic cysts. In contrast, follicles in ovPCO are primarily atretic, analogous to the situation in the normal ovary. Closer analysis of the function of these follicles reveals an intrinsic defect in the theca cell layer in the expression of the genes encoding steroidogenic enzymes. Although androgen production is increased in all PCOs, the serum concentrations of androgen tended to be higher in anovulatory women indicating that there may be a link between the ovarian concentration and anovulation. Granulosa cells in small follicles from anovPCO behave in a similar fashion to those in preovulatory follicles from normal ovaries in terms of steroidogenic responses. This, in combination with the finding of LH-responsiveness in small follicles from anovPCO, has led to the suggestion that these follicles are prematurely luteinized. The recent finding that follistatin gene regulation may be abnormal in women with polycystic ovary syndrome (PCOS) provides a new insight into the possible defect in the function of these ovaries. Elucidation of the precise nature of the defect may provide the key to understanding the apparent contradiction of increased steroidogenesis in the presence of abnormal and arrested follicle growth.

The analysis of two active regions on the limb using observations from SOHO-CDS allows us to determine the electron density and temperature distribution of the coronal emission. We find that the active regions have hot cores (3×106 K) with larger cooler (106 K) loop structures extending above the limb. The electron number density, determined using the Si X diagnostic line ratio, is found to be highest in the active region core (greater than 2.3×109 cm−3). Electron number density values are determined for a range of spectral lines from different ions and are found to increase with temperature between 0.8 and 2.5×106 K. These results are consistent with recent models of enhanced heating along the compact core of active regions, where the magnetic field shear is strongest.

Helen Mason explains how men are making an impact in the early years through an innovative music programme in Lincolnshire.

The appropriate thresholds for decisions on the cost-effectiveness of medical interventions remain controversial, especially in 'end-of-life' situations. Evidence of the values placed on different types of health gain by the general public is limited.Across nine European countries, 17,657 people were presented with different hypothetical health scenarios each involving a gain of one quality adjusted life year (QALY) and asked about their willingness to pay (WTP) for that gain. The questions included quality of life (QoL) enhancing and life extending health gains, and a scenario where respondents faced imminent, premature death.The mean WTP values for a one-QALY gain composed of QoL improvements were modest (PPP$11,000). When comparing QALY gains obtained in the near future, the valuation of life extension exceeded the valuation of QoL enhancing gains (mean WTP PPP$19,000 for a scenario in which a coma is avoided). The mean WTP values were higher still when respondents faced imminent, premature death (PPP$29,000).Evidence from the largest survey on the value of health gains by the general public indicated a higher value for life extending gains compared with QoL enhancing gains. A further modest premium may be indicated for life extension when facing imminent, premature death.

The elicitation of societal views about healthcare priority setting is an important, contemporary research area, and there are a number of studies that apply either qualitative techniques or quantitative preference elicitation methods. However, there are methodological challenges in connecting qualitative information (what perspectives exist about a subject) with quantitative questions (to what extent are those perspectives 'supported' in a wider population). In this paper, we present an integrated, mixed-methods approach to the elicitation of public perspectives in two linked studies applying Q methodology. In the first study, we identify three broad viewpoints on the subject of health priorities. In the second study, using Q-survey methods, we describe and illustrate methods to investigate the distribution of those views in the wider population. The findings of the second study suggest that no single viewpoint dominates and none of the three views represents a 'minority perspective'. We demonstrate the potential of Q methodology as a methodological framework that can be used to link qualitative and quantitative questions and suggest some advantages of this over other approaches. However, as this represents the first applied study of this kind, there are methodological questions that require further exploration and development.

Aims: To measure the prevalence, pattern and associated financial cost of alcohol-related ambulance call outs in the North East of England using routinely collected data from the North East Ambulance Service (NEAS). Methods: A retrospective cohort study over a 1-year time period (1 April 2009 to 31 March 2010) using NEAS patient record forms. Results: In the North East, 10% of ambulance call outs were alcohol-related. Males were 2.5 times more likely than females to be attended by an ambu- lance on the street rather than at home. People aged 10-19 had the highest relative risk ratio (3.4) of an ambulance pick up being on the street compare with those aged over 60. These call outs and subsequent accident and emergency (A&E) attendances cost over £9 million in a 1-year period. When extrapolated to the whole country the cost could be as much as £152 million per year. Conclusion: In a 1-year period, we estimated that over 31,000 ambulance call outs were alcohol-related. A large discrepancy was found between manual and electronic recording of alcohol-related ambulance attendances to A&E. The workload and cost of alcohol-related call outs is high and mostly preventable. Ambulance visits may present a teachable moment for brief intervention to reduce alcohol- related risk and harm.

Graft-versus-host disease is uncommon in autologous hematopoietic cell transplantation (HCT) and is typically brief and mild. We report unusual, protracted, and severe Omenn syndrome-like autoaggression following autologous HCT. We identified a profound FOXP3 + regulatory T cell defect that coincided with hyperinflammatory T cell responses which were reversible with rapamycin in vitro .

Recently, for many health economics researchers, empirical estimation of the monetary valuation of a quality-adjusted life year (QALY) has become an important endeavour. Different philosophical and practical approaches to this have emerged. On the one hand, there is a view that, with health-care budgets set centrally, decision-making bodies within the system can iterate, from observation of a series of previous decisions, towards the value of a QALY, thus searching for such a value. Alternatively, and more consistent with the approach taken in other public sectors, individual members of the public are surveyed with the aim of directly eliciting a preference-based – also known as a willingness-to-pay-based (WTP-based) – value of a QALY. While the former is based on supply-side factors and the latter on demand, both in fact suffer from informational deficiencies. Sole reliance on either would necessitate an acceptance or accommodation of chronic inefficiencies in health-care resource allocation. On the basis of this observation, this paper makes the case that in order to approach optimal decision making in health-care provision, a framework incorporating and thus, to a degree, reconciling these two approaches is to be preferred.

Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England,\ud there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether\ud QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY\ud (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were\ud released during a time of considerable debate about the NICE threshold, and authors with differing perspectives\ud have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of\ud results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for\ud those who conducted the research to contribute to the debate as to its implications for NICE.\ud Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the\ud current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and\ud age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’\ud answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in\ud values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values\ud of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing\ud the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the\ud other that greater weight could be given to QALYs gained by some groups.\ud Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling\ud evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be\ud moved up for some types of QALY and down for others. While many members of the public appear to be open to\ud the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have\ud any secure evidence base for introducing such a system.

We compared naive CD4 and CD8 T-cell homeostasis in primary progressive multiple sclerosis (PPMS), relapsing-remitting MS (RRMS) and controls. Quantitation of signal joint T-cell receptor (TCR) excision circles (sjTRECs) and quantitative estimates of daily thymic export confirm our previous report of reduced thymic output in RRMS and demonstrate reduced thymic output in PPMS. In PPMS, the decreasing % CD31+ naive CD4 T-cells but constant sjTRECs and constant naive CD4 T-cell numbers with age, together with increased Bcl-2 expression suggest increased TCR signaling with increased naive T-cell survival. We conclude PPMS patients have peripheral immune alterations related to reduced thymic output.

To identify characteristics of beneficiaries of health care over which relative weights should be derived and to estimate relative weights to be attached to health gains according to characteristics of recipients of these gains (relativities study); and to assess the feasibility of estimating a willingness-to-pay (WTP)-based value of a quality-adjusted life-year (QALY) (valuation study).Two interview-based surveys were administered - one (for the relativities study) to a nationally representative sample of the population in England and the other (for the valuation study) to a smaller convenience sample.The two surveys were administered by the National Centre for Social Research (NatCen) in respondents' homes.587 members of the public were interviewed for the relativities study and 409 for the valuation study.In the relativities study, in-depth qualitative work and considerations of policy relevance resulted in the identification of age and severity of illness as relevant characteristics. Scenarios reflecting these, along with additional components reflecting gains in QALYs, were presented to respondents in a series of pairwise choices using two types of question: discrete choice and matching. These questions were part of a longer questionnaire (including attitudinal and sociodemographic questions), which was administered face to face using a computer-assisted personal interview. In the valuation study, respondents were asked about their WTP to avoid/prevent different durations of headache or stomach illness and to value these states on a scale (death = 0; full health = 1) using standard gamble (SG) questions.Discrete choice results showed that age and severity variables did not have a strong impact on respondents' choices over and above the health (QALY) gains presented. In contrast, matching showed age and severity impacts to be strong: depending on method of aggregation, gains to some groups were weighted three to four times more highly than gains to others. Results from the WTP and SG questions were combined in different ways to arrive at values of a QALY. These vary from values which are in the vicinity of the current National Institute for Health and Clinical Excellence (NICE) threshold to extremely high values.With respect to relative weights, more research is required to explore methodological differences with respect to age and severity weighting. On valuation, there are particular issues concerning the extent to which 'noise' and 'error' in people's responses might generate extreme and unreliable figures. Methods of aggregation and measures of central tendency were issues in both weighting and valuation procedures and require further exploration.

An assay based on the inhibition of syncytium formation in C8166 cells was developed to measure low levels of neutralising antibody (NT-AB) to human immunodeficiency virus (HIV) and to detect cross-reactivity between virus strains. The relationship between virus challenge and antibody titre was represented by a tripartite curve which was essentially linear over moderate levels of virus input. Based on these findings, antibody titres were standardised against 100 TCID50 of challenge virus. However, lower virus inocula were found to detect minimum levels of antibody. Reproducibility of antibody titres between tests was high, with variation generally lying within one dilution step. The improved sensitivity of the technique allowed detection of NT-ABs in animals immunised with immune-stimulating complexes (ISCOMS) incorporating HIV antigens. Consistent levels of cross-reactivity between HIV strains was demonstrated, indicating the presence of distinct viral groups, from which dominant isolates may be chosen for use in vaccination studies.

We investigated naive CD4 T-cell homeostasis in relapsing–remitting multiple sclerosis (RRMS). Quantification of signal joint T-cell receptor excision circles in FACS-isolated CD31hi cells, which correspond closely to CD4 recent thymic emigrants (RTEs), indicates that young patients have reduced generation of CD4 RTEs compared to age-matched controls. In RRMS, compared to controls, CXCR4 analyses indicate age-associated thymic output of progressively immature CD4 RTEs, and Ki-67 data demonstrate altered T-cell proliferative responses that fail to maintain naive CD4 T-cell numbers with age. Thus, RRMS patients have early thymic involution with compensatory homeostatic peripheral T-cell proliferative responses that may predispose patients to autoreactivity.

Debate about the monetary value of a quality-adjusted life year (QALY) has existed in the health economics literature for some time. More recently, concern about such a value has arisen in UK health policy. This paper reports on an attempt to 'model' a willingness-to-pay-based value of a QALY from the existing value of preventing a statistical fatality (VPF) currently used in UK public sector decision making. Two methods of deriving the value of a QALY from the existing UK VPF are outlined: one conventional and one new. The advantages and disadvantages of each of the approaches are discussed as well as the implications of the results for policy and health economic evaluation methodology.

For reasons that are unclear, skin from various body sites has different permeability properties. We have used hydrophilic penetrants (water, ethanol, mannitol, and paraquat) to study the in vitro permeability of skin from marmoset (eight body sites), man, and rat. Skin structure (stratum corneum thickness and number of cell layers; epidermal and dermal thickness; number and area of hair follicle openings per mm2) was compared with permeability. There was no apparent relationship between skin structure and permeability to the most rapid penetrants, water and ethanol. Follicle area opening was the structural feature that varied most between species and between body sites. Different marmoset body sites showed a threefold range in follicle area but this did not appear to influence the absorption rates of the test penetrants. However, among the species there was an 80-times range in follicle area, which correlated with the observed differences in rate of mannitol and paraquat absorption. Thus, permeability could be related to inter-species differences in skin structure, but only with the relatively slowly absorbed test penetrants, mannitol and paraquat.

Background Advance Care Planning (ACP) is an approach to achieving patient-centred decision making, which is a recognised mechanism for improving value, and improving a range of health outcomes. Whilst ACP has begun to gain momentum in New Zealand, there remains potential for further impact through systematic implementation. Aim To identify the key success factors and barriers to implementation of ACP and make recommendations on policy and strategic approaches to achieve sustainable implementation of ACP at scale. Methods A case study approach forms the principal method of inquiry. Four leading US organisations were selected based on; literature review; advice from key informants and selection criteria. Site visits, and in-depth interviews with a range of clinical and managerial staff were undertaken. Results The research is scheduled for completion in August 2015. Expected outcomes include the importance of a systems approach encompassing; public education and engagement; professional development; decision support aids; availability of appropriate service provision (palliative/hospice care); aligned policy and funding systems. A deliberate change management strategy to support these elements is anticipated to be a key factor for success. Discussion The recommendations from the research are expected to be of significance to a range of stakeholders. New Zealand has policy settings which recognise the importance of patient-centred care. Full realisation of the benefits has not been achieved to date. Conclusion Effective implementation of ACP on a national scale requires a systems approach, incorporating a range of key elements. Success is dependent on a deliberate change management strategy.

Objectives: There is little empirical evidence to guide clinical practice in treating adult patients presenting to Adult Mental Health and Primary Care services with severe psychological difficulties consequent on childhood sexual abuse. The aim of this study was to determine the effectiveness of a model of short term, focal, integrative psychotherapy with this population of patients and to compare outcomes when the model is delivered on an individual or group basis. Design: This study used a patient preference design with random allocation to one of two treatment modalities (individual or group treatment). There was a waiting list control. Method: Forty-eight women patients were assessed on four psychological measures when entering a waiting list condition, immediately before treatment and after completion of 12 sessions of psychotherapy, either in a group or individually. Follow up data were collected at 4 months and 8 months. Results: Both individual and group patients showed highly statistically and clinically significant improvements after treatment. These gains were maintained at follow up with the exception of one measure that indicated a significant decline from post treatment levels for the group patients. Conclusions This model of psychotherapy is highly effective, when delivered by chartered clinical psychologists to patients whose preferences for individual or group therapy have been met.

The CHIANTI atomic database contains atomic energy levels, wavelengths, radiative transition probabilities and electron excitation data for a large number of ions of astrophysical interest. Version 4 has been released, and proton excitation data is now included, principally for ground configuration levels that are close in energy. The fitting procedure for excitation data, both electrons and protons, has been extended to allow 9 point spline fits in addition to the previous 5 point spline fits. This allows higher quality fits to data from close-coupling calculations where resonances can lead to significant structure in the Maxwellian-averaged collision strengths. The effects of photoexcitation and stimulated emission by a blackbody radiation field in a spherical geometry on the level balance equations of the CHIANTI ions can now be studied following modifications to the CHIANTI software. With the addition of H I, He I and N I, the first neutral species have been added to CHIANTI. Many updates to existing ion data-sets are described, while several new ions have been added to the database, including Ar IV, Fe VI and Ni XXI. The two-photon continuum is now included in the spectral synthesis routines, and a new code for calculating the relativistic free-free continuum has been added. The treatment of the free-bound continuum has also been updated., Comment: CHIANTI is available at http://wwwsolar.nrl.navy.mil/chianti.html

Olaparib is an oral inhibitor of the Poly-(ADP-ribose)-polymerases (PARP-1, -2 and -3), and has demonstrated clinical activity in trials of patients with BRCA-deficient tumors. The BRCA1 and BRCA2 proteins are both important for the repair of DNA double strand breaks (DSBs) by homologous recombination repair (HRR) and sensitivity to olaparib has further been shown preclinically to extend to other DNA DSB repair factor deficiencies, including those in the ataxia telangiectasia mutated (ATM) protein. We have demonstrated that a high proportion of gastric cancer (GC) cell lines (∼50%) are responsive (IC50 Based on these data, a Phase II GC trial has been carried out that enriches for patients with tumors having low or undetectable ATM IHC scores (H-score equivalent less than or equal to 10). Data from this clinical trial confirm activity (overall survival [OS] benefit HR=0.56, 95% CI: 0.35-0.87; P=0.010) in the overall population, which includes ATM tumor positive patients, and importantly, a substantially better OS benefit in the ATM-negative population (HR=0.35, 95% CI: 0.17-0.71; P=0.003). Together, these data provide an important example of a PARP inhibitor demonstrating both preclinical and clinical activity in a well defined but non-BRCA DNA repair deficient background. Citation Format: Darren Hodgson, Helen Mason, Lenka Oplustilova, Chris Harbron, Xiaolu Yin, Seock-Ah Im, Helen Jones, Lai Zhongwu, Brian Dougherty, Matthew McLoughlin, James Bradford, Andrew Dickinson, Anitra Fielding, Jane Robertson, Woo-Ho Kim, Chris Womack, Yi Gu, Yung-Jue Bang, Alan Lau, J. Carl Barrett, Mark J. O'Connor. Activity of the PARP inhibitor olaparib in ATM-deficient gastric cancer: from preclinical models to the clinic. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2398. doi:10.1158/1538-7445.AM2014-2398

Background Coronary heart disease (CHD) remains a leading cause of UK mortality, generating a large and unequal burden of disease. CHD costs the UK in excess of £6 billion annually, with estimated statins costs exceeding £840 million. Dietary trans fats represent a powerful CHD risk factor. However, UK efforts to reduce intake (currently approximately 1% of daily energy) have been less successful than some other nations, such as Denmark and the USA. Furthermore, the potential heath and economic outcomes of a legislative ban, and the effects upon health inequalities, have not been well quantified. We therefore aimed to model the potential health and economic effects of a UK legislative ban on industrial trans fats up to 2030. Methods We extended the previously validated IMPACTsec model, to estimate the potential effects of a ban on dietary industrial trans fats upon the England and Wales population aged over 25 years. We stratified these estimates by age, sex and socio-economic circumstances. Data sources included Hospital Episode Statistics, General Practice Registry Database, and Office of National Statistics. Cost data was sourced from Department of Health, NICE and British Retail Consortium. We estimated the subsequent economic effects of a legislative ban upon healthcare, informal care, productivity, and industry and the disease burden (expected CHD deaths, life years gained (LYGs), Quality adjusted life years (QALYs) and hospital admissions) over a 15 year horizon to 2030. The baseline results were tested in a probabilistic sensitivity analysis. Results A legislative ban on industrial trans fats across the England and Wales population, reducing intake to 0.5% of daily energy intake would result in approximately 5468 fewer deaths per year, (95% confidence intervals (CI) 5459–5477), with some 6000 fewer hospital admissions (95% CI 5300–6700); and gaining approximately 43,400 additional life years (95% CI 43,200–43,700). This would also reduce health inequalities, having a substantially larger beneficial effect upon mortality and LYGs in the most deprived, than the most affluent. A legislative ban could result in savings in excess of approximately £2 billion and generate gains of over 400,000 QALYs over a 15 year period. This would include annual savings of approximately £16 million in direct healthcare costs, some £50 million productivity gains and approximately £70 million savings in informal care costs. Industry reformulation costs would be relatively small. Conclusion Eliminating the UK dietary intake of industrial trans fats could substantially decrease CHD mortality, whilst also resulting in substantial savings annually. Urgent fiscal or legislative action is warranted.

Introduction: Patients with colorectal cancer report ongoing physical and psychological impairments and a high proportion of these patients are overweight, insufficiently active and high-risk drinkers, putting them at risk of poor recovery and risk of recurrence and comorbidities. A challenge is implementing sustainable and effective rehabilitation as part of routine care for this group.\ud \ud Methods and analysis: A two-arm pilot randomised controlled trial (RCT) with embedded feasibility study undertaken as a phased programme of work. The intervention involves an existing cardiac rehabilitation programme for cardiac patients accepting colorectal cancer patient referrals. The intervention consists of supervised exercise sessions run by a cardiac physiotherapist and information sessions. Phase 1 will involve one research site enrolling 12 patients to assess intervention and study design processes. Semistructured interviews with patients with colorectal cancer and cardiac patients and clinicians will be used to gather data on acceptability of the intervention and study procedures. Phase 2 will involve three sites enrolling 66 patients with colorectal cancer randomised to control or intervention groups. Outcome measures will be taken preintervention and postintervention, for phases 1 and 2. The primary outcome is accelerometer measured physical activity; secondary outcomes are self-report physical activity, quality of life, anxiety, depression, symptoms including fatigue. The following variables will also be examined to determine if these factors influence adherence and outcomes: self-efficacy, risk perception and treatments.\ud \ud Ethics and dissemination: Full ethical approval was granted by NRES Committees—North of Scotland (13/NS/0004; IRAS project ID: 121757) on 22 February 2013. The proposed work is novel in that it aims to test the feasibility and acceptability of using an evidence-based and theory driven existing cardiac rehabilitation service with patients with colorectal cancer. Should this model of rehabilitation prove to be clinically and cost effective we aim to conduct a randomised controlled trial of this intervention to measure effectiveness.\ud \ud Trial registration reference: ISRCTN63510637; UKCRN id 14092.

Some of the main factors that affect the determination of the element abundances from EUV spectra are reviewed. The ionization balance, the selection of lines, and the spectroscopic method used can each account for a variation of a factor of two or more in the derived element abundances, in particular cases. Diagnostic techniques are applied to Skylab/HCO and SOHO/CDS observations of solar coronal holes and plumes, in order to derive their relative element abundances. It is confirmed that coronal holes have photospheric abundances, while plumes only show a small FIP effect, contrary to what has long been thought. It is shown that the plume characteristics can mainly be explained in terms of their temperature structure rather than a large FIP effect.

The Solar and Heliospheric Observatory (SOHO) carries several ultraviolet spectrometers to diagnose the plasma conditions of the solar atmosphere in order to address several outstanding questions in solar research: why is the corona hot and how is the solar wind accelerated. Diagnostic techniques for determining the magnetohydrodynamic state (magnetic field, density, temperature, velocity) are discussed. We describe the CHIANTI database which has been designed to provide the necessary spectroscopic diagnostics for these data as well as for other spectroscopic missions. The database is built on 3 main files for each ion: atomic energy levels, radiative data, and electron collisional data. The electron collision strengths are assessed and scaled using the Burgess and Tully scaling laws. Analyses of EUV line intensities often reveal discrepancies between observed and predicted line intensities of about of 2 when considering lines of the same ion. A more recent analysis has shown that it is possible to arrive...

The Coronal Diagnostic Spectrometer (CDS) has as a scientific goal the determination of the physical parameters of the solar plasma using spectroscopic diagnostic techniques. Absolute intensities and intensity ratios of the EUV spectral emission lines can be used to obtain information on the electron density and temperature structure, element abundances, and dynamic nature of different features in the solar atmosphere. To ensure that these techniques are accurate it is necessary to interface solar analysis programs with the best available atomic data calculations. Progress is reported on this work in relation to CDS observations.

Background The incidence of coronary heart diseases is increasing in the occupied Palestinian territory (oPt) and hence poses a growing challenge for treatment. Reduction in the intake of dietary salt is a potentially cost-effective approach to reduce the burden of coronary heart diseases. Here, we report the results of an economic assessment of three interventions of salt reduction in the oPt. Methods We did the analysis from a societal perspective of three salt-reduction interventions—population-wide health promotion campaigns, mandatory labelling of food packaging, and mandatory reduction of salt content of processed food. These interventions were assessed individually, and in combinations of two and all three together. We estimated the costs of policies using past experiences, expert opinion, and hospital records, and costs of health care with a standardised unit cost for treatments. We considered the financial implications for the food industry and public sectors. The total cost of implementation of each policy was compared with the do-nothing scenario. We used data reported in reviews of epidemiological studies as estimates of the expected reduction of the current sodium salt consumption attributable to each policy. The expected change in salt intake was then converted into a change in mean population blood pressure based on estimates reported in a meta-analysis. The change in blood pressure was used to estimate the number of deaths prevented or postponed in 10 years, using the Palestinian IMPACT policy model for coronary heart disease. The estimates were compared with the number of deaths from coronary heart disease that would have been expected in relation to the number in the baseline year. This policy model is an epidemiological model that was used to analyse mortality associated with coronary heart disease and risk factor trends in the West Bank, oPt, between 1998 and 2009, and project mortality trends for the future. We used Microsoft Excel 2010 for our analyses. Findings All policies resulted in a reduction in salt intake of 5–30%, leading to changes of 1–20 mm Hg in systolic blood pressure. All scenarios were cost effective compared with the do-nothing scenario. The cost-effectiveness of the scenarios for per life-year gained was $134·57–1430·62 (purchasing power parity at 2010 exchange rates). Policies for the labelling of food and use of the three interventions together were the most cost effective. These two scenarios were estimated to save costs ($9 million and $6 million) and resulted in 945 life-years gained and 2682 life-years gained, respectively. Interpretation Reduction of salt intake reduces the long-term burden of coronary heart diseases. In the oPt, population-based interventions to reduce salt intake are not only cost effective but also cost saving. We recommend a population-wide health promotion campaign, mandatory labelling of food packaging, and mandatory reduction of salt content of processed food. Funding European Community's Seventh Framework Programme.

Background Coronary heart disease (CHD) and stroke account for approximately half of all-deaths in Syria. The country’s CHD mortality rate has escalated by nearly two-thirds between 1996 and 2006, partly reflecting substantial increases in systolic blood pressure (SBP). In high income countries, reduction of dietary salt intake represents a cost effective means of decreasing CHD events via reduced SBP levels. This study aims to assess the potential costs and benefits of implementing contrasting salt reduction policies in Syria, with particular emphasis on the feasibility of policies within the country’s socioeconomic and political realities. Methods A projected 10-year period cost-effectiveness analysis of salt reduction policies was conducted comparing three different approaches: health promotion campaign about salt reduction, labelling of salt content on packaged foods, reformulation of salt content within packaged foods, or a comprehensive strategy involving all three approaches. The incremental cost of a policy was calculated as the sum of CHD-related savings in healthcare costs and the costs of implementing and monitoring the policy, with costs presented in international dollars using 2010 purchasing power parity (PPP) exchange rates. Benefits were defined as life years gained (LYG) due to fewer CHD events. Data sources included existing national resources, international literature, and interviews with local food producers, manufacturers, and government agencies. The effect of salt reduction on SBP was based on review of the literature. Health care costs, LYG and expected CHD events were calculated using the IMPACT CHD model. Sensitivity analyses were conducted to account for the uncertainty in the reduction of salt intake. Results All policy combinations resulted in LYG when compared to no policy. Health promotion and labelling of salt content were both associated with low private sector costs and large healthcare savings. This resulted in cost savings for both policies alone and the comprehensive approach combining all three policies. Reformulation alone, reformulation plus health promotion, and reformulation plus labelling were not cost saving due to high private sector costs associated with reformulation (+PPP $96,000,000). However, the three policy approaches were very cost-effective with incremental costs of $5453 PPP, $2125 PPP, and $2201 PPP per LYG, respectively (well below the region’s established cost effectiveness threshold of PPP$12,250). Conclusion All salt reduction policies analysed resulted in a reduction of CHD deaths and were either cost-effective or even cost saving. This paper will provide further details concerning the feasibility of such policies in the context of a developing country.