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The chemistry and aerosols in ice core records are used as proxy data for the past climate. Traditional interpretation of this recorded climate signal is that during formation snow captures a snapshot of the atmosphere. In recent years, observations have documented that the snow surface’s chemistry and isotopic composition change during the post-depositional interaction with the surface-near atmosphere. To more accurately interpret the climate signal in ice cores it is necessary to understand thesource of the water vapor in the planetary boundary layer (PBL), as well as the vertical mixing and transportation in the polar atmosphere. However, the dynamics in the polar PBL are poorly constrained in most climate models due to a lack of observations. Here we present insights from the first Arctic in-situ water-vapor isotope record both within and above the PBL up to 1500 meters above the Greenland Ice Sheet (GrIS) from the EastGRIP ice core camp 2022 field campaign. Flights were performed with a fixed-wing uncrewed aircraft recording high resolution atmospheric profiles. Moreover, air is sampled in glass flasks and brought to the surface for determination of δ18O and δDof water vapor. The observational set-up has been proven to guarantee reliable measurements of the isotopic composition of the atmospheric water vapor in remote locations and under extremely cold temperatures. Based on 105 observed temperature, humidity and isotopic profiles we identify different types of atmospheric structure above the GrIS. We evaluate the vertical atmospheric representation of the polar regional climate model MAR and the isotope-enabled global climate model ECHAM-wiso. Finally, from observations we estimate the height up to which the surface-near δ18O and δD isotopic values are affected by the atmosphere above.

Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and is regulated by subcellular organelles. Here, we tested the hypothesis that NLRP3 senses disrupted endosome trafficking to trigger inflammasome formation and inflammatory cytokine secretion. NLRP3-activating stimuli disrupted endosome trafficking and triggered localization of NLRP3 to vesicles positive for endolysosomal markers and for the inositol lipid PI4P. Chemical disruption of endosome trafficking sensitized macrophages to the NLRP3 activator imiquimod, driving enhanced inflammasome activation and cytokine secretion. Together, these data suggest that NLRP3 can sense disruptions in the trafficking of endosomal cargoes, which may explain in part the spatial activation of the NLRP3 inflammasome. These data highlight mechanisms that could be exploited in the therapeutic targeting of NLRP3.

Hayley Bennett interviews Significance’s newest editorial board member, Claire McKay Bowen. A data privacy expert at non-profit, The Urban Institute, a research organisation based in Washington, DC, Claire works on new ways to help people access sensitive data so that it can be used for public good. She’s also the author of Protecting Your Privacy in a Data-Driven World.

Ian Gordon has spent 40 years working as an applied statistician and was recently appointed President of the Statistical Society of Australia (SSA). As director of the Statistical Consulting Centre at the University of Melbourne, his clients are diverse and he has acted as an expert witness in high-profile legal cases, including for victims of fires, floods, racial discrimination and pelvic mesh implants. Hayley Bennett finds out more

Democracies are under pressure and public administrations must evolve to accommodate new forms of public participation. Participation processes may reproduce or disrupt existing power inequalities. Through a multi-method empirical study of “Participation Requests,” a new legislative policy tool to open up public services in Scotland, this article addresses an empirical gap on governance-driven democratic innovations (DIs). We use Young’s distinction of external and internal inclusion and find Participation Requests replicate the pitfalls of traditional forms of associative democracy. We contend that DIs should be co-produced between institutions and communities to bring a participatory and deliberative corrective to temper bureaucratic logics.

The formation of healthy tissue involves continuous remodeling of the extracellular matrix (ECM). Whilst it is known that this requires integrin-associated cell-ECM adhesion sites (CMAs) and actomyosin-mediated forces, the underlying mechanisms remain unclear. Here, we examine how tensin3 contributes to the formation of fibrillar adhesions (FBs) and fibronectin fibrillogenesis. Using BioID mass spectrometry and a mitochondrial targeting assay, we establish that tensin3 associates with the mechanosensors such as talin and vinculin. We show that the talin R11 rod domain binds directly to a helical motif within the central intrinsically disordered region (IDR) of tensin3, whilst vinculin binds indirectly to tensin3 via talin. Using CRISPR knock-out cells in combination with defined tensin3 mutations, we show (i) that tensin3 is critical for the formation of α5β1-integrin FBs and for fibronectin fibrillogenesis, and (ii) the talin/tensin3 interaction drives this process, with vinculin acting to potentiate it.

UK employment policy is at a critical juncture; the effects of COVID-19 and Brexit on the labour market have heightened pre-existing and created new employment and income inequalities. Such experiences (and related temporary government policy responses) play out alongside the long-term roll-out of Universal Credit, a social security policy that imposes conditionality on a range of individuals, including people who are in work. As Universal Credit has the potential to transform power dynamics between individuals, the state and employers, revisiting and questioning the direction of active labour market policies (ALMPs) should unite the interests of diverse social security and employment researchers. Policymakers should draw on an abundance of research to reform the UK’s ALMPs and avoid replicating the problems of narrowly conceived work-first programmes and practices. In this chapter, we explore the role of social policy researchers in influencing policy change, reflecting on our own experiences as early career researchers. We advocate a ‘pragmatic realist’ approach to policy engagement and reflect on different approaches to operating at the evidence–policy interface.

Background Structural uncertainty can affect model-based economic simulation estimates and study conclusions. Unfortunately, unlike parameter uncertainty, relatively little is known about its magnitude of impact on life-years (LYs) and quality-adjusted life-years (QALYs) in modeling of diabetes. We leveraged the Mount Hood Diabetes Challenge Network, a biennial conference attended by international diabetes modeling groups, to assess structural uncertainty in simulating QALYs in type 2 diabetes simulation models. Methods Eleven type 2 diabetes simulation modeling groups participated in the 9th Mount Hood Diabetes Challenge. Modeling groups simulated 5 diabetes-related intervention profiles using predefined baseline characteristics and a standard utility value set for diabetes-related complications. LYs and QALYs were reported. Simulations were repeated using lower and upper limits of the 95% confidence intervals of utility inputs. Changes in LYs and QALYs from tested interventions were compared across models. Additional analyses were conducted postchallenge to investigate drivers of cross-model differences. Results Substantial cross-model variability in incremental LYs and QALYs was observed, particularly for HbA1c and body mass index (BMI) intervention profiles. For a 0.5%-point permanent HbA1c reduction, LY gains ranged from 0.050 to 0.750. For a 1-unit permanent BMI reduction, incremental QALYs varied from a small decrease in QALYs (−0.024) to an increase of 0.203. Changes in utility values of health states had a much smaller impact (to the hundredth of a decimal place) on incremental QALYs. Microsimulation models were found to generate a mean of 3.41 more LYs than cohort simulation models ( P = 0.049). Conclusions Variations in utility values contribute to a lesser extent than uncertainty captured as structural uncertainty. These findings reinforce the importance of assessing structural uncertainty thoroughly because the choice of model (or models) can influence study results, which can serve as evidence for resource allocation decisions. Highlights The findings indicate substantial cross-model variability in QALY predictions for a standardized set of simulation scenarios and is considerably larger than within model variability to alternative health state utility values (e.g., lower and upper limits of the 95% confidence intervals of utility inputs). There is a need to understand and assess structural uncertainty, as the choice of model to inform resource allocation decisions can matter more than the choice of health state utility values.

There is a shift in university-based social research towards interdisciplinary working and collaboration with non-academic partners, which requires a reconsideration of methodological concepts and research practices. In this article, we draw on intensive collaborative action research (CAR) into public service reform to demonstrate how this ‘collaborative shift’ both challenges and creates new considerations for mainstream research approaches. We contend that the contemporary emphasis on research collaborations creates challenges for both social science researchers and non-academic partners, which require greater conceptual consideration. Researchers need to engage in distinctive, significant and ongoing relational, pragmatic and political work in multi-agency contexts. We present the concept of a ‘buffer zone’: a dynamic, contextual space and set of practices necessary to undertake participatory research within complex and changeable settings. This has implications for research management, design, funding and training.

INTRODUCTION Patients dying a short time after receiving palliative radiation are unlikely to have received benefit and may experience harm. To monitor the potential for avoidable harm, 30-day mortality following palliative radiation has been recommended for use as a quality indicator and the Royal College of Radiologist have recommended a rate of lower than 20%. At the Canterbury Regional Cancer and Haematology Service in Christchurch, New Zealand (CRCHS), we investigated 30-day mortality and evaluated the prognostic value of the TEACHH model in our population. METHODS Palliative treatments from two, two-year periods (2012/2013 and 2016/2017) were retrospectively reviewed. We analysed 30-day mortality and several influencing variables. Patients were divided into three groups using the TEACHH model (type of cancer, performance status, age, prior palliative chemotherapy, prior hospitalizations and hepatic metastases). RESULTS There were 1744 patients; 30-day mortality was 10% and was higher in patients with lung cancer (17% vs. 8% in non-lung cancer patients, P

When asked for a commentary on the roles and responsibilities of nonindigenous researchers in indigenous cancer research, several potential nonindigenous coauthors were contacted. The majority wanted to “run for the hills,” signifying that many researchers feel uncomfortable, out of their depth, and fearful regarding methodologies and principles for safe and effective research with and for indigenous peoples. Most health research is relevant for indigenous peoples, and most researchers are nonindigenous. Thus, if researchers don’t engage with indigenous research principles, health research can and does result in significant harm for indigenous peoples.1,2 Nonengagement may also prevent potential positive outcomes for indigenous communities (eg, health gain, workforce and community development) and impinge on indigenous rights to health and development.3 In this commentary, we outline our reflections and observations on the roles and responsibilities of nonindigenous cancer researchers and identify some of the principles that guide researchers in Aotearoa (Aotearoa is the name given by the indigenous Māori for New Zealand). We do not attempt to provide an in-depth analysis or comprehensive best practice summary, but hope to encourage more discussion in this critical and evolving area.

Background Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD); however, the natural course of disease progression is heterogeneous between patients. This study aimed to develop a natural history model of ADPKD that predicted progression rates and long-term outcomes in patients with differing baseline characteristics. Methods The ADPKD Outcomes Model (ADPKD-OM) was developed using available patient-level data from the placebo arm of the Tolvaptan Efficacy and Safety in Management of ADPKD and its Outcomes Study (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948). Multivariable regression equations estimating annual rates of ADPKD progression, in terms of total kidney volume (TKV) and estimated glomerular filtration rate, formed the basis of the lifetime patient-level simulation model. Outputs of the ADPKD-OM were compared against external data sources to validate model accuracy and generalisability to other ADPKD patient populations, then used to predict long-term outcomes in a cohort matched to the overall TEMPO 3:4 study population. Results A cohort with baseline patient characteristics consistent with TEMPO 3:4 was predicted to reach ESRD at a mean age of 52 years. Most patients (85%) were predicted to reach ESRD by the age of 65 years, with many progressing to ESRD earlier in life (18, 36 and 56% by the age of 45, 50 and 55 years, respectively). Consistent with previous research and clinical opinion, analyses supported the selection of baseline TKV as a prognostic factor for ADPKD progression, and demonstrated its value as a strong predictor of future ESRD risk. Validation exercises and illustrative analyses confirmed the ability of the ADPKD-OM to accurately predict disease progression towards ESRD across a range of clinically-relevant patient profiles. Conclusions The ADPKD-OM represents a robust tool to predict natural disease progression and long-term outcomes in ADPKD patients, based on readily available and/or measurable clinical characteristics. In conjunction with clinical judgement, it has the potential to support decision-making in research and clinical practice. Electronic supplementary material The online version of this article (10.1186/s12882-017-0804-2) contains supplementary material, which is available to authorized users.

BACKGROUND AND AIMS The hepatitis C virus (HCV) remains a considerable public health challenge. Novel direct-acting antiviral (DAA) regimens offer high cure rates and the promise of reduced HCV incidence and prevalence following the up-scaling of treatment. This has focused attention towards affordability. This study aimed to estimate the economic value of cure to evaluate the treatment costs justifiable from the patient perspective. PATIENTS AND METHODS A published, validated HCV model was utilized to contrast clinical and cost outcomes for patients aged 30-70 years, stratified by METAVIR F0-F4, for (i) no treatment and (ii) successful treatment [i.e. sustained virologic response (SVR)] ignoring the cost of treatment. Regression equations were fitted and used to determine the financial expenditure justifiable to achieve a cost-neutral or a cost-effective [£20 000 per quality-adjusted life-year (QALY)] cure. Model inputs were derived from UK literature; costs and utilities were discounted at 3.5% over a lifetime horizon. RESULTS To achieve cost-neutrality, the maximum discounted expenditure justifiable for SVR was £3774-43 607 across ages and fibrosis stages. Spending between £19 745 (70 years, F0) and £188 420 (30 years, F4) on SVR is expected to be cost-effective at £20 000/QALY willingness-to-pay threshold. CONCLUSION Heterogeneity across HCV patients is considerable, which can obscure the relevance of conventional cohort-based economic models evaluated at the mean, particularly when considering the value of treatment at the individual patient level. By quantifying the full exposition of HCV cost-savings and health benefits realizable following HCV cure, this study provides insight into the economic value of successful treatment from the patient perspective.

Insulin-treatment in type 1 diabetes mellitus (T1DM) is associated with elevated risk of hypoglycaemia and weight gain, which may act as a barrier to achieving optimal glycaemic control. For patients inadequately controlled by insulin alone, adjunct dapagliflozin can reduce body weight and improve glycaemic control without increased risk of hypoglycaemia. This study aimed to empirically quantify the inter-relationships between hypoglycaemia, body mass index (BMI) and quality of life using DEPICT-2 trial data. A two-stage linear regression framework evaluated (1) the relationship between hypoglycaemic fear score (HFS) and the occurrence of severe hypoglycaemia, the number of documented symptomatic events and patient age, and (2) the relationship between health-related utility (EQ-5D) and prognostic factors for utility, including HFS and BMI. Model selection was based on clinically-relevant factors. A linked evidence approach correlated the relationship between treatment, hypoglycaemia incidence and HbA1c over 52-weeks, to the relationships captured within the regression models. HFS increased as a function of incidence of severe hypoglycaemia (coefficient estimate (CE): 14.62, p=0.004) and frequency of symptomatic events (log transposed, CE: 1.32, p=0.0026). In turn, increased HFS and increased BMI were both independently associated with a significant reduction in utility (CE 0.0024, p Disclosure J. Gordon: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Takeda Canada, Takeda Pharmaceutical Company Limited. L.M. Beresford-Hulme: None. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. A. Tank: Employee; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd.

For many sufferers of anorexia nervosa, the time course is long, and the prospect of disability and family burden great. This is all too often the case, even with early diagnosis and treatment. The term severe and enduring anorexia nervosa has been applied to these survivors. Yet, a majority of patients do eventually recover and, even where this is not the case, adaptive medical stability and function can be maintained despite alarming dilapidation. Managing the years of illness so as to have the best outcome physically and psychologically, even where full weight recovery does not occur, or has not yet occurred, is the topic of this article. Literature pertaining to harm minimization in chronic, severe, enduring, and long-standing anorexia nervosa was selectively reviewed using an Ovid data base and Google Scholar. The authors' own clinical experience over almost four decades in public and private hospital and community settings has also informed much of what has been written. The authors would like to think that it is possible to do better than the familiar injunction (variously attributed to Hippocrates, Galen, and others) of 'primum non nocere'-although this is a good place to start.

With current health ministerial directives to prioritise actions on reducing health inequities and district health board (DHB) greenhouse gas (GHG) emissions, we argue that all climate change and environmental sustainability actions by DHBs must be pro-equity, and explore how the two priorities can be addressed concurrently.Building on prior knowledge of climate change and environmental sustainability action in the health and disability sector, we undertook a visioning exercise to generate ideas for pro-equity GHG emissions reduction initiatives in the DHB context. Visioning was further informed by presentation and feedback discussion at an Annual Scientific Meeting of the New Zealand College of Public Health Medicine.Three scenarios were envisioned in the areas of DHB energy use, transport and procurement where GHG emissions could be reduced, and health determinants and outcomes for Māori and Pacific peoples improved.Current ministerial directives to address both health inequities and DHB greenhouse gas emissions present DHBs with the opportunity to ensure they systematically address both priorities at the same time. In doing so, Aotearoa/New Zealand has the potential to lead the world in demonstrating pro-equity climate change and sustainability action in health systems.

Variance covariance matrices for TKV and eGFR progression equation coefficients. Table S1. Variance covariance matrix for the TEMPO 3:4 TKV equation coefficients. Table S2. Variance covariance matrix for the TEMPO 3:4 eGFR equation coefficients. Example of using the TKV and eGFR progression equations to predict annual ADPKD progression. Applying the ADPKD-OM to alternative patient populations. Using CKD-Epi measurements to model eGFR progression. Table S3. Comparison of eGFR progression equation coefficient estimates. Table S4. Variance covariance matrix for the TEMPO 3:4 eGFR equation coefficients. Validation against CRISP I-derived progression equations. CRISP I-derived equations for TKV (Equation S1) and eGFR (Equation S2) progression. Table S5. TKV progression equation coefficient estimates, as derived from CRISP I. Table S6. eGFR progression equation coefficient estimates, as derived from CRISP I. Validation against HALT-PKD trial data. Validation against THIN data. Validation against Thong and Ong [40]. Equation S3. eGFR progression equation, derived by Thong and Ong [40]. Table S7. eGFR progression equation coefficient estimates, as derived from Thong and Ong [40]. (DOCX 51 kb)

Objectives. Type 2 diabetes mellitus (T2DM) clinical guidelines focus on optimizing glucose control, with therapy escalation classically initiated within a “failure-based” regimen. Within many diabetes models, HbA1c therapy escalation thresholds play a pivotal role, controlling duration of therapy and, consequently, incremental costs and benefits. The objective of this study was to assess the relationship between therapy escalation threshold and time to therapy escalation on predicted cost-effectiveness of T2DM treatments. Methods. This study used the Cardiff Diabetes Model to illustrate the relationship between costs and health outcomes associated with first-, second-, and third-line therapy as a function of time on each. Data from routine clinical practice were used to contrast predicted costs and health outcomes associated with guideline therapy escalation thresholds compared with clinical practice. The impact of baseline HbA1c and therapy escalation thresholds on cost-effectiveness was investigated, comparing a sodium/glucose cotransporter 2 inhibitor v. sulfonylurea added to metformin monotherapy. Results. Lower thresholds are associated with a shorter time spent on monotherapy, ranging from 1.1 years (escalation at 6.5%) to 13 years (escalation at 9.0%) and an increase in total lifetime cost of therapy. Treatment-related disutility is minimized with higher thresholds because progression to insulin is delayed. Using metformin combined with either dapagliflozin or a sulfonylurea to illustrate lower baseline HbA1c and/or higher therapy escalation thresholds was associated with increased cost-effectiveness ratios, driven by a longer duration of therapy. Discussion. A marked difference in treatment cost-effectiveness was demonstrated when comparing routine clinical practice with guideline-advocated therapy escalation. This is important to both health care professionals and the wider health economic community with respect to understanding the true cost-effectiveness profile of any particular T2DM therapy option.

Since 1997 Kick It Out has worked as a charitable organization that promotes equality and inclusion, as well as challenging all forms of discrimination in English football. Prior to this, and since its formation in 1993, the organization had worked under the name of Let’s Kick Racism Out of Football as a campaign against racism within the game. Since 2012, the remit of the organization has broadened and it works both proactively and reactively within football and the communities around it. Kick It Out is widely recognized in football and society due to its campaigning activities that raise awareness of the ongoing issues relating to equality, diversity and discrimination in football. However, there still often exists a lack of awareness of the organization’s day-to-day work in challenging discrimination, breaking down barriers and making the sport more inclusive.

This article critically reflects on the administration of activation services in the UK. It describes the welfare-to-work quasi-market and focuses on the impact of 2008 commissioning reforms that advocated amalgamating small contracts into larger ‘lots’, creating a top tier of prime providers to manage subcontractors, and increasing outcome-based funding. Drawing on transaction cost theory and empirical case study research, it is demonstrated that these changes led to an increase in a range of activities and costs for competing service providers that undermine government rhetoric of choice and efficiency. This article adds to the existing literature on welfare-to-work contracting by demonstrating the difficulties some organisations face in the context of welfare markets and questioning public service out-sourcing processes. It concludes by reflecting on the implications for future market-based social policy reforms.

The aim of this paper is to estimate the relative cost-effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed based on information from the findings from a systematic review of clinical effectiveness and cost-effectiveness, published sources of unit costs, and expert opinion. The assumption was that patients presenting with sciatica would be managed through one of 3 pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12-month period. One-way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was nonopioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was nonopioids, followed by biological agents, followed by epidural/nerve block and disk surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost-effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per quality-adjusted life year are higher, the economic model demonstrated that stepped approaches based on initial treatment with nonopioids are likely to represent the most cost-effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required.

Background. This study aims to describe the healthcare resource utilization and costs of managing renal posttransplant patients over 3 years posttransplant in nine European countries and to stratify them by year 1 glomerular filtration rate (GFR). Methods. A retrospective observational and database analysis of renal transplant patients and a physician questionnaire study were conducted to collect recipient and donor characteristics, posttransplant events, and healthcare resource utilization related to these posttransplant events. In each country, local published costs were applied to the resource use identified. The results were stratified by the patient GFR reading at a time point 1 year after renal transplant. Results. The database study identified 3,181 patients who met the inclusion criteria, along with 2,818 transplants carried out in the centers surveyed by questionnaire. Total 3-year costs derived from the questionnaire analysis vary depending on local treatment practices, from a minimum of €33,602 per patient in the Czech Republic to €77,461 per patient in the Netherlands. Consistently across countries, estimated costs appear to decrease with improved graft functioning status (increased GFR) at 1 year. The average 3-year costs, discounting immunosuppresion therapy and certain posttransplant events, per patient with a GFR greater than or equal to 60 at 1 year are estimated to be around 35% lower than those with 15eGFRG30. Conclusion. This study demonstrates that in Europe, worsening posttransplant renal function may contribute to substantive increases in resource use, with some variation across regions. Therefore, management strategies that promote renal function after transplantation have the potential to provide important resource savings.

Background: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in early breast cancer patients. This study aims to examine the implications of routine Oncotype DX testing in the UK. Methods: Women with oestrogen receptor positive (ER+), pNO or pN1mi breast cancer were assessed for adjuvant chemotherapy and subsequently offered Oncotype DX testing, with changes in chemotherapy decisions recorded. A subset of patients completed questionnaires about their uncertainties regarding chemotherapy decisions pre- and post-testing. All patients were asked to complete a diary of medical interactions over the next 6 months, from which economic data were extracted to model the cost-effectiveness of testing. Results: Oncotype DX testing resulted in changes in chemotherapy decisions in 38 of 142 (26.8%) women, with 26 of 57 (45.6%) spared chemotherapy and 12 of 85 (14.1%) requiring chemotherapy when not initially recommended (9.9% reduction overall). Decision conflict analysis showed that Oncotype DX testing increased patients' confidence in treatment decision making. Economic analysis showed that routine Oncotype DX testing costs £6232 per quality-adjusted life year gained. Conclusion: Oncotype DX decreased chemotherapy use and increased confidence in treatment decision making in patients with ER+ early-stage breast cancer. Based on these findings, Oncotype DX is cost-effective in the UK setting.

Using a case study of Glasgow, UK, this chapter discusses the design and delivery of anti-poverty activities in a post-industrial left-wing city located within a national liberal welfare model. Focusing on the multi-level architecture of the British welfare state, the chapter draws attention to the local arrangement and institutional relations between organisations engaged in employment, social service and broadly speaking, anti-poverty work in the city. As well as outlining the role of public and non-public sector organisations, Bennett explores issues of partnership working, competing initiatives and the politics of poverty. This chapter outlines the levers local actors utilise to deliver anti-poverty services and reflects on multi-level tensions, competing agendas and conflicting ways of working.

Discovering methods to combat poverty and social exclusion has now become a major political challenge in Europe. This book offers an original and timely analysis of how actors at the European, national and subnational levels meet this challenge. Combining perspectives on multilevel and network coordination, the editors discuss to what extent actors join forces in these efforts and identify the factors limiting the coordination achieved in practice. The book builds on a European study comparing Germany, Italy, Poland, Sweden and the UK.

This article compares the welfare markets in primary health care and ‘welfare‐to‐work’ in the UK since the late 1990s. A longitudinal comparison of two different policy areas enables us to study the context in which marketization and the resulting shift of welfare provision takes place. We outline the general background of the market‐based reforms and highlight in what way policymakers have ascribed third sector organizations (TSOs) a number of positive characteristics, particularly the ability to address concerns about well‐known market failures. While consecutive governments promoted these organizations as welfare providers, case studies of two illustrative provider organizations in each policy area reveal a number of problems regarding their distinctiveness in increasingly competitive welfare markets.We conclude that the crisp distinction made by policymakers between the third and other sectors as well as the alleged advantages of the former present a rather naïve picture of a complex reality and argue for a more critical view of third sector characteristics and performance. The third sector is not only characterized by a high degree of fuzziness at the boundaries to other sectors, but even within single organizations, which often undergo significant transformations over time. As a result, policy intentions and practical outcomes are contradictory with TSOs losing their alleged distinctiveness as players in increasingly competitive markets. Furthermore, we contend that detailed longitudinal studies of organizations are essential in the advancement of the discussion of the third sector concept as they provide conceptual insights into organizational change and behaviour.

Objective This study aimed to determine the cost-effectiveness of daclatasvir in combination with other medicinal products for the treatment of patients with hepatitis C virus genotypes 1 and 4 and advanced liver disease in the UK. Methods A published and validated Markov model designed to simulate the natural history of chronic hepatitis C was used to compare daclatasvir with relevant treatment options for patients with hepatitis C virus genotypes 1 and 4 and a METAVIR score of F3-F4. Patients were defined according to their treatment status; that is, naive, experienced or interferon ineligible/intolerant. Data inputs for the analysis were derived from published sources, UK-specific where possible. A lifetime horizon was used, with costs and benefits discounted at 3.5%. Results Daclatasvir-based regimens are estimated to be cost-effective versus no treatment and established standard-of-care regimens, including telaprevir in combination with pegylated interferon-α+ribavirin (PR), boceprevir in combination with PR and PR alone (incremental cost-effectiveness ratio range: £3715-£15,408). The cost-effectiveness of daclatasvir-based regimens versus emerging regimens (sofosbuvir or simeprevir based) is less consistent, but was dominant or cost-effective (incremental cost-effectiveness ratio range: £1394-£28,393) in all except two scenarios. Conclusion Daclatasvir-based regimens are expected to be highly cost-effective for the majority patients with advanced disease versus relevant comparator regimens, including newer direct-acting antiviral regimens.

Health and wellbeing have been largely ignored in discussions around climate change targets and action to date. The current public consultation around New Zealand's post-2020 climate target is an opportunity for health professionals to highlight the health implications of climate change. Without urgent global efforts to bring down global GHG (greenhouse gas) emissions, the world is heading towards high levels of global warming, which will have devastating impacts on human health and wellbeing. New Zealand's action to bring down GHG emissions (as part of the global effort) has potential to improve health and reduce costs on the health sector, if health and fairness are put at the centre of policies to address climate change. New Zealand should commit to at least 40 % reductions in GHG emissions by 2030, and zero carbon emissions before 2050, with healthy and fair policies across sectors to enable reaching these targets.

Introduction Hepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40–80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR. Methods A published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies. Results QALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £300), increasing to £49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively. Conclusion Projecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.

Climate change is widely regarded as one of the most serious global health threats of the 21st century. Its impacts will be disproportionately borne by the most disadvantaged populations, including indigenous peoples. For Māori in Aotearoa/New Zealand, as with other indigenous peoples worldwide, colonization has led to dispossession of land, destabilization of cultural foundations, and social, economic, and political marginalization. Climate change threatens to exacerbate these processes, adding future insult to historical and contemporary injury. Yet the challenges posed by climate change are accompanied by considerable opportunities to advance indigenous rights and reduce health disparities. In this paper, we examine issues related to climate change and Māori health using a right to health analytical framework, which identifies obligations for the New Zealand government.