Unmanageable Debt and Financial Difficulty in the English and Welsh Civil and Social Justice Survey: Report for the Money Advice Trust

The following report uses three years of data from the English and Welsh Civil and Social Justice Survey (CSJS), a face-to-face household survey of people’s experience of and response to rights problems, to examine respondents who reported problems associated with unmanageable debt and financial difficulty. The research was commissioned by the Money Advice Trust with the aim of enriching and supporting existing research regarding people in debt, with reference to adviceseeking strategies, impact of debt problems, and the interrelationship between debt and other problems

Civil Justice in England and Wales, 2009: Report of the 2006-2009 English and Welsh Civil and Social Justice Survey

People’s ability to use the law to protect their rights and hold others to their responsibilities is crucial to ensuring fairness before the law, bringing about social justice and addressing social exclusion. The ‘Continuous’ English and Welsh Civil and Social Justice Survey (CSJS), conducted between 2006 and 2009, examines this in detail. This report describes the main findings from the Continuous English and Welsh Civil and Social Justice Survey

Systolic and diastolic ventricular function in zebrafish embryos: Influence of norepenephrine, MS-222 and temperature

<p>Abstract</p> <p>Background</p> <p>Zebrafish are increasingly used to study the influences of gene mutation and manipulation on cardiac development, structure and function. In this study, a video edge detection system was used to characterise, continuously, cardiac ventricle function in 2–5 days old zebrafish embryos embedded in 0.6% agar and examined under light microscopy at room temperature (22°C). Using video edge detection software (IonOptix Inc), the motion of a small region of the cardiac ventricle wall was converted to a continuous chart trace allowing analysis of wall motion amplitude (WMA) and myocardial wall velocity during systole (MWVs) and diastole (MWVd).</p> <p>Results</p> <p>Cardiac wall motion characteristics changed progressively from day 2 to 5 (WMA, 2-days, 17.6 ± 4.4 μm vs 5-days, 24.6 ± 4.7 μm, p < 0.01). MWVd was more rapid than MWVs at all developmental time points. Embryonic hearts were also assessed after increasing concentrations of norepenephrine (NE) and the anaesthetic agent MS222 (tricaine) were added to the bathing water. In response to NE, WMA increased significantly more in 4 day embryos compared with 2 day embryos (change in WMA,13.6 ± 8.2 μm vs 4.0 ± 8.8 μm, p = 0.01, respectively) while the decrease in WMA in response to MS222 was similar in both 2 and 4-day embryos. Heart rate, MWVs and MWVd were significantly higher at 28°C compared with 22°C. No differences in cardiac function were observed between AB and Golden strains.</p> <p>Conclusion</p> <p>Video edge detection appears sufficiently sensitive to detect subtle changes in diastolic and systolic cardiac function during development and changes resulting from pharmacological and environmental interventions. Such measurements could be valuable in assessment of altered cardiac function after genetic manipulation.</p

Towards durable multistakeholder-generated solutions: The pilot application of a problem-oriented policy learning protocol to legality verification and community rights in Peru

This paper reports and reflects on the pilot application of an 11-step policy learning protocol that was developed by Cashore and Lupberger (2015) based on several years of Cashore’s multi-author collaborations. The protocol was applied for the first time in Peru in 2015 and 2016 by the IUFRO Working Party on Forest Policy Learning Architectures (hereinafter referred to as the project team). The protocol integrates insights from policy learning scholarship (Hall 1993, Sabatier 1999) with Bernstein and Cashore’s (2000, 2012) four pathways of influence framework. The pilot implementation in Peru focused on how global timber legality verification interventions might be harnessed to promote local land rights. Legality verification focuses attention on the checking and auditing of forest management units in order to verify that timber is harvested and traded in compliance with the law. We specifically asked: How can community legal ownership of, and access to, forestland and forest resources be enhanced? The protocol was designed as a dynamic tool, the implementation of which fosters iterative rather than linear processes. It directly integrated two objectives: 1) identifying the causal processes through which global governance initiatives might be harnessed to produce durable results ‘on the ground’; 2) generating insights and strategies in collaboration with relevant stakeholders. This paper reviews and critically evaluates our work in designing and piloting the protocol. We assess what seemed to work well and suggest modifications, including an original diagnostic framework for nurturing durable change. We also assess the implications of the pilot application of the protocol for policy implementation that works to enhance the influence of existing international policy instruments, rather than contributing to fragmentation and incoherence by creating new ones

Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors

Th17 cells contribute to host defense on mucosal surfaces but also provoke autoimmune diseases when directed against self-antigens. Identifying therapeutic targets that regulate Th17 cell differentiation and/or cytokine production has considerable value. Here, we study the aryl hydrocarbon receptor (AhR)-dependent transcriptome in human CD4 T cells treated with Th17-inducing cytokines. We show that the AhR reciprocally regulates IL-17 and IL-22 production in human CD4 T cells. Global gene expression analysis revealed that AhR ligation decreased IL21 expression, correlating with delayed upregulation of RORC during culture with Th17-inducing cytokines. Several of the AhR-dependent genes have known roles in cellular assembly, organization, development, growth and proliferation. We further show that expression of GPR15, GPR55 and GPR68 positively correlates with IL-22 production in the presence of the AhR agonist FICZ. Activation of GPR68 with the lorazepam derivative ogerin resulted in suppression of IL-22 and IL-10 secretion by T cells, with no effect on IL-17. Under neutral Th0 conditions, ogerin and the Gq/11 receptor inhibitor YM254890 blunted IL-22 induction by FICZ. These data reveal the AhR-dependent transcriptome in human CD4 T cells and suggest the mechanism through which the AhR regulates T cell function may be partially dependent on Gq-coupled receptors including GPR68

RGS16, a novel p53 and pRb cross-talk candidate inhibits migration and invasion of pancreatic cancer cells

Data collected since the discovery of p53 and pRb/RB1 suggests these tumor suppressors cooperate to inhibit tumor progression. Patients who have mutations in both p53 and RB1 genes have increased tumor reoccurrence and decreased survival compared to patients with only one tumor suppressor gene inactivated. It remains unclear how p53 and pRb cooperate toward inhibiting tumorigenesis. Using RNA expression profiling we identified 179 p53 and pRb cross-talk candidates in normal lung fibroblasts (WI38) cells exogenously coexpressing p53 and pRb. Regulator of G protein signaling 16 (RGS16) was among the p53 and pRb cross-talk candidates and has been implicated in inhibiting activation of several oncogenic pathways associated with proliferation, migration, and invasion of cancer cells. RGS16 has been found to be downregulated in pancreatic cancer patients with metastases compared to patients without metastasis. Expression of RGS16 mRNA was decreased in the pancreatic cancer cell lines tested compared to control. Expression of RGS16 inhibited migration of the BxPC-3 and AsPC-1 but not PANC-1 cells and inhibited invasion of BxPC-3 and AsPC-1 cells with no impact on cell viability. We have identified for the first time p53 and pRb cross-talk candidates and a role for RGS16 to inhibit pancreatic cancer migration and invasion

Imaging the Developing Heart: Synchronized Timelapse Microscopy During Developmental Changes

How do you use imaging to analyse the development of the heart, which not only changes shape but also undergoes constant, high-speed, quasi-periodic changes? We have integrated ideas from prospective and retrospective optical gating to capture long-term, phase-locked developmental time-lapse videos. In this paper we demonstrate the success of this approach over a key developmental time period: heart looping, where large changes in heart shape prevent previous prospective gating approaches from capturing phase-locked videos. We use the comparison with other approaches to in vivo heart imaging to highlight the importance of collecting the most appropriate data for the biological question.Comment: Carl J. Nelson and Charlotte Buckley and John J. Mullins and Martin A. Denvir and Jonathan Taylor, "Imaging the Developing Heart: Synchronized Timelapse Microscopy During Developmental Changes", Proc. SPIE (10499), 10499-41 (2018). Copyright 2018 Society of Photo Optical Instrumentation Engineers (SPIE

Identifying Acute Coronary Syndrome Patients Approaching End-of-Life

Background: Acute coronary syndrome (ACS) is common in patients approaching the end-of-life (EoL), but these patients rarely receive palliative care. We compared the utility of a palliative care prognostic tool (Gold Standards Framework (GSF)) and the Global Registry of Acute Coronary Events (GRACE) score, to help identify patients approaching EoL. Methods and Findings: 172 unselected consecutive patients with confirmed ACS admitted over an eight-week period were assessed using prognostic tools and followed up for 12 months. GSF criteria identified 40 (23%) patients suitable for EoL care while GRACE identified 32 (19%) patients with $10 % risk of death within 6 months. Patients meeting GSF criteria were older (p = 0.006), had more comorbidities (1.660.7 vs. 1.260.9, p = 0.007), more frequent hospitalisations before (p = 0.001) and after (0.0001) their index admission, and were more likely to die during follow-up (GSF+ 20 % vs GSF- 7%, p = 0.03). GRACE score was predictive of 12-month mortality (C-statistic 0.75) and this was improved by the addition of previous hospital admissions and previous history of stroke (C-statistic 0.88). Conclusions: This study has highlighted a potentially large number of ACS patients eligible for EoL care. GSF or GRACE could be used in the hospital setting to help identify these patients. GSF identifies ACS patients with more comorbidity and at increased risk of hospital readmission

Global analysis of gene expression changes during retinoic acid-induced growth arrest and differentiation of melanoma: comparison to differentially expressed genes in melanocytes vs melanoma

<p>Abstract</p> <p>Background</p> <p>The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-<it>trans</it>-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood.</p> <p>Results</p> <p>In an analysis of sequential global gene expression changes during a 4–48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and B16 melanoma cells. Using the same statistical test, we found 1495 genes whose expression was significantly higher in melan-a than in B16 cells and 2054 genes whose expression was significantly lower in melan-a than in B16 cells. By intersecting these two gene sets, we discovered a common set of 233 genes whose RNA levels were significantly different between B16 and melan-a cells and whose expression was altered by RA treatment. Within this set, RA treatment altered the expression of 203 (87%) genes toward the melan-a expression level. In addition, hierarchical clustering showed that after 48 h of RA treatment expression of the 203 genes was more closely related to the melan-a gene set than any other RA treatment time point. Functional analysis of the 203 gene set indicated that RA decreased expression of mRNAs that encode proteins involved in cell division/cell cycle, DNA replication, recombination and repair, and transcription regulation. Conversely, it stimulated genes involved in cell-cell signaling, cell adhesion and cell differentiation/embryonic development. Pathway analysis of the 203 gene set revealed four major hubs of connectivity: CDC2, CHEK1, CDC45L and MCM6.</p> <p>Conclusion</p> <p>Our analysis of common genes in the 48 h RA-treatment of B16 melanoma cells and untreated B16 vs. melan-a data set show that RA "normalized" the expression of genes involved in energy metabolism, DNA replication, DNA repair and differentiation. These results are compatible with the known growth inhibitory and pro-differentiating effects of RA. Pathway analysis suggests that CDC2, CHEK1, CDC45L and MCM6 are key players in mediating the biological activity of RA in B16 melanoma cells.</p

Palliative care needs in patients hospitalized with heart failure (PCHF) study: rationale and design

Abstract Aims The primary aim of this study is to provide data to inform the design of a randomized controlled clinical trial (RCT) of a palliative care (PC) intervention in heart failure (HF). We will identify an appropriate study population with a high prevalence of PC needs defined using quantifiable measures. We will also identify which components a specific and targeted PC intervention in HF should include and attempt to define the most relevant trial outcomes. Methods An unselected, prospective, near-consecutive, cohort of patients admitted to hospital with acute decompensated HF will be enrolled over a 2-year period. All potential participants will be screened using B-type natriuretic peptide and echocardiography, and all those enrolled will be extensively characterized in terms of their HF status, comorbidity, and PC needs. Quantitative assessment of PC needs will include evaluation of general and disease-specific quality of life, mood, symptom burden, caregiver burden, and end of life care. Inpatient assessments will be performed and after discharge outpatient assessments will be carried out every 4 months for up to 2.5 years. Participants will be followed up for a minimum of 1 year for hospital admissions, and place and cause of death. Methods for identifying patients with HF with PC needs will be evaluated, and estimates of healthcare utilisation performed. Conclusion By assessing the prevalence of these needs, describing how these needs change over time, and evaluating how best PC needs can be identified, we will provide the foundation for designing an RCT of a PC intervention in HF