The age of austerity: the impact of welfare reform on people in the North East of England

According to Mark Carney the Governor of the Bank of England the United Kingdom economic outlook is getting brighter: "For the first time in a long time you don’t have to be an optimist to see the glass is half full. The recovery has finally taken hold (Carney 2013).” Unemployment is falling; as have interest rates and GDP (Gross Domestic Product) growth has been upgraded from 2.5 per cent to 2.8 per cent for the year 2014. Despite these “green shoots of recovery”, the impact of government austerity measures and social policy decisions means the outlook for millions of citizens remains blea

Linked lives: the utility of an agent-based approach to modelling partnership and household formation in the context of social care

The UK’s population is aging, which presents a challenge as older people are the primary users of health and social care services. We present an agent-based model of the basic demographic processes that impinge on the supply of, and demand for, social care: namely mortality, fertility, health-status transitions, internal migration, and the formation and dissolution of partnerships and households. Agent-based modeling is used to capture the idea of “linked lives” and thus to represent hypotheses that are impossible to express in alternative formalisms. Simulation runs suggest that the per-taxpayer cost of state-funded social care could double over the next forty years. A key benefit of the approach is that we can treat the average cost of state-funded care as an outcome variable, and examine the projected effect of different sets of assumptions about the relevant social processes

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

Small, Slow, and Local

The United States is in the middle of a significant cultural shift. Until very recently, United States citizens and policy-makers were willing to accept, or at least tolerate, what has become our food status quo--a highly subsidized, centralized, industrial food system that is environmentally harmful and unsustainable and encourages unhealthy eating habits. Many citizens and policy-makers are now demanding that we re-evaluate our entire agricultural system from farm to table and look for ways to develop a new food paradigm that is environmentally sound, sustainable, socially equitable, and that makes healthy whole foods available to all. During the summer of 2010, I taught a course titled Agricultural Policy and the Environment at Vermont Law School. When I walked into the classroom on the first day I was shocked to see almost fifty students in the class. I taught the same course the year before and had approximately twenty-five students in the class. Although I cannot be sure, I think that if I taught the same course ten years ago I would be lucky to have enough students register to avoid having the course cancelled. Not only did the 2010 course have a very large enrollment, but the students who were in the course were extremely interested and engaged and brought with them a broad range of relevant experience. Some had grown up on farms in various parts of the country while others had chosen to work on organic farms as teenagers or adults. Some students had previously or were currently working on agricultural or food policy matters through a variety of organizations such as land trusts and in a variety of capacities such as being a social worker. Many others, while not having as much direct experience, had learned a great deal about agricultural and food policy through other formal education or independently. The widespread interest in agricultural issues at Vermont Law School mirrors the renewed interest in food policy by the public in general. Unquestionably, many factors contribute to this cultural shift to local foods, including a desire to feel more connected to the land and to interact more with our communities. However, certainly a major factor is the public\u27s growing awareness that our current industrialized food system has failed us with regard to the health of both our diets and the environment

Stakeholder perspectives of a pilot multicomponent delirium prevention intervention for adult patients with advanced cancer in palliative care units: A behaviour change theory-based qualitative study

Background: Theory-based and qualitative evaluations in pilot trials of complex clinical interventions help to understand quantitative results, as well as inform the feasibility and design of subsequent effectiveness and implementation trials. Aim: To explore patient, family, clinician and volunteer (‘stakeholder’) perspectives of the feasibility and acceptability of a multicomponent non-pharmacological delirium prevention intervention for adult patients with advanced cancer in four Australian palliative care units that participated in a phase II trial, the ‘PRESERVE pilot study’. Design: A trial-embedded qualitative study via semi-structured interviews and directed content analysis using Michie’s Behaviour Change Wheel and the Theoretical Domains Framework. Setting/participants: Thirty-nine people involved in the trial: nurses (n = 17), physicians (n = 6), patients (n = 6), family caregivers (n = 4), physiotherapists (n = 3), a social worker, a pastoral care worker and a volunteer. Results: Participants’ perspectives aligned with the ‘capability’, ‘opportunity’ and ‘motivation’ domains of the applied frameworks. Of seven themes, three were around the alignment of the delirium prevention intervention with palliative care (intervention was considered routine care; intervention aligned with the compassionate and collaborative culture of palliative care; and differing views of palliative care priorities influenced perspectives of the intervention) and four were about study processes more directly related to adherence to the intervention (shared knowledge increased engagement with the intervention; impact of the intervention checklist on attention, delivery and documentation of the delirium prevention strategies; clinical roles and responsibilities; and addressing environmental barriers to delirium prevention). Conclusion: This theory-informed qualitative study identified multiple influences on the delivery and documentation of a pilot multicomponent non-pharmacological delirium prevention intervention in four palliative care units. Findings inform future definitive studies of delirium prevention in palliative care

Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated:a retrospective longitudinal UK cohort study

Abstract Background Current clinical guidelines recommend treating chronic hepatitis B virus (HBV) infection in a minority of cases, but there are relatively scarce data on evolution or progression of liver inflammation and fibrosis in cases of chronic HBV (CHB) that do not meet treatment criteria. We aimed to assess the impact of TDF on liver disease, and the risk of renal impairment in treated CHB patients in comparison to untreated patients. Methods We studied a longitudinal ethnically diverse CHB cohort in the UK attending out-patient clinics between 2005 and 2018. We examined TDF treatment (vs. untreated) as the main exposure, with HBV DNA viral load (VL), ALT, elastography scores and eGFR as the main outcomes, using paired tests and mixed effects model for longitudinal measurements. Additionally, decline of eGFR during follow-up was quantified within individuals by thresholds based on clinical guidelines. Baseline was defined as treatment initiation for TDF group and the beginning of clinical follow-up for untreated group respectively. Results We included 206 adults (60 on TDF, 146 untreated), with a median ± IQR follow-up duration of 3.3 ± 2.8 years. The TDF group was significantly older (median age 39 vs. 35 years, p = 0.004) and more likely to be male (63% vs. 47%, p = 0.04) compared to the untreated group. Baseline difference between TDF and untreated groups reflected treatment eligibility criteria. As expected, VL and ALT declined significantly over time in TDF-treated patients. Elastography scores normalised during treatment in the TDF group reflecting regression of inflammation and/or fibrosis. However, 6/81 (7.4%) of untreated patients had a progression of fibrosis stage from F0-F1 to F2 or F3. There was no evidence of difference in rates or incidence of renal impairment during follow-up in the TDF vs. untreated group. Conclusions Risk of liver inflammation and fibrosis may be raised in untreated patients compared to those receiving TDF, and TDF may benefit a larger percentage of the CHB population

Estimating the sensitivity of a prostate cancer screening programme for different PSA cut-off levels:A UK case study

Policy decisions about prostate cancer screening require data on the natural history of histological cancers and the resulting impact of screening. However, the gold standard procedure required to identify true positive histological cancer is a full autopsy of the gland which is not possible in screening studies, leading to verification bias. We aim to estimate the sensitivity of a prostate cancer screening round (PSA result to diagnosis) relative to histological cancer.We developed a framework combining data on UK screened and non-screened prostate cancer populations originating from a single round of population-based PSA testing among UK men aged 50-69 years, prostate cancer incidence data, and needle biopsy data from the published literature.Sensitivity of a screening round was highest at age 65-69 years at 33% (95% CI: 30%-37%) and 24% (95% CI: 21%-28%) for PSA cut-off levels of 3 ng/ml and 4 ng/ml, respectively. Sensitivity was lowest at age 50-54 at 15% (95% CI: 12%-17%) and 9% (95% CI: 8%-11%) for PSA cut-off levels of 3 ng/ml and 4 ng/ml, respectively. In contrast, the clinical detection rate in the absence of mass screening, relative to histological cancer, varied between 0.2%-0.7% at age 50-54 and 1.2%-2.7% at age 65-69 from 1995 to 2012.The framework enabled the sensitivity of a prostate cancer screening round relative to histological cancer diagnosis to be estimated and provides a basis to determine the impact and cost-effectiveness of prostate cancer screening. The approach could be adapted to inform the sensitivity of other biomarkers, cancers and screening programmes

Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach

Structure-guided expansion of a fragment hit for the ATAD2 bromodomain enabled improvement in ATAD2 inhibition and selectivity over BRD4.</p