Syntheses of potentially conducting polymers containing fluorine

The preparation and characterisation of a number of fluorinated monomers capable of electrochemical polymerisation is described. Their electrochemical characteristics and the products of polymerisation are discussed 4,5,6,7-Tetrafluoroisothianaphthene was synthesised and its chemistry investigated. Attempts to electrochemically polymerise this to give a potentially narrow band-gap conducting polymer were generally unsuccessful. Other analogous monomers were also found to be difficult to polymerise by this method. New fluorinated polyphenylylenevinylene oligomers and polymers have been prepared. In addition, potential routes to high molecular weight polytetrafluorophenylenevinylenes have been being investigated. Oligomeric poly-2,3,5,6-tetrafluorophenylenevinylenes were prepared via a self nucleophilic displacement of the para fluorine in cis and trans organometallic derivatives of corresponding cis and trans 1-halo- 2-pentafluorphenylethenes.The attempted preparation of poly 2,3,5,6-tetrafluorophenylene- vinylene via two different soluble precursor derivatives is described. 2,3,5,6-tetrafluoro-l,4-xylene-bis(dialkyl sulphonium halides) were prepared with view to the preparation of soluble precursor derivatives of F-PPV. Preliminary work polymerising 2,3,5,6-tetrafluorobenzene- 1,4-diethanal with 1,4-dilithium-2,3,5,6-tetrafluorobenzene did provide polyalcohol type precursor polymers to F-PPV, but requires further developement

Deprivation in New Zealand: Regional Patterns and Changes

This paper presents an analysis of the distribution of socio- economic deprivation throughout New Zealand. The analysis focuses on the three census years 1986, 1991, and 1996. A summary deprivation measure is constructed which approximates New ZealandDep96 using standard regression techniques. The paper extends a static analysis of deprivation by examining changes to the deprivation profile across time on a regional basis. Differences in the incidence of deprivation for different ethnic groups are emphasised. Maori and Pacific people are more likely to live in deprived meshblocks than their European counterparts. We also touch on the role isolation plays in determining the distribution of deprivation.deprivation; inequality; distribution; meshblocks; regions

Modelling Regional Labour Market Adjustment in New Zealand

This paper adopts a vector autoregressive (VAR) approach to analyse the labour market adjustment mechanisms for 12 New Zealand regions over the period 1985 to 2001. It examines the effects of a region-specific shock to employment on itself, the unemployment rate, the participation rate, and the wage rate. The role of migration as a channel of regional labour market adjustment is also inferred. We find that adjustment occurs predominantly through inter-regional migration although the unemployment and participation rates also play a role. Wages, on the other hand, account for very little adjustment. The importance of inter-regional migration in New Zealand matches the results found in Sweden, but stands in contrast to the picture in many European countries. Migration appears to be a more dominant adjustment channel compared to the US and Australian cases. However, this has to be placed into context – New Zealand regions are much smaller in terms of population size.Regional labour market adjustment; Internal migration

N<i>e</i>XOS – the design, development and evaluation of a rehabilitation system for the lower limbs

Recent years have seen the development of a number of automated and semi-automated systems to support for physiotherapy and rehabilitation. These deploy a range of technologies from highly complex purpose built systems to approaches based around the use of industrial robots operating either individually or in combination for applications ranging from stroke to mobility enhancement. The NeXOS project set out to investigate an approach to the rehabilitation of the lower limbs in a way which brought together expertise in engineering design and mechatronics with specilists in rehabilitation and physiotherapy. The resulting system has resulted in a prototype of a system which is capable in operating in a number of modes from fully independent to providing direct support to a physiotherapist during manipulation of the limb. Designed around a low cost approach for an implementation ultimately capable of use in a patients home using web-baased strategies for communication with their support team, the prototype NeXOS system has validated the adoption of an integrated approach to its development. The paper considers this design and development process and provides the results from the initial tests with physiotherapists to establish the operational basis for clinical implementation

MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity

Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread

Overcoming alcohol and other drug addiction as a process of social identity transition : the social identity model of recovery (SIMOR)

In recent years, there has been an increasing focus on a recovery model within alcohol and drug policy and practice. This has occurred concurrently with the emergence of community- and strengths-based approaches in positive psychology, mental health recovery and desistance and rehabilitation from offending. Recovery is predicated on the idea of substance user empowerment and self-determination, using the metaphor of a ‘‘journey’’. Previous research describing recovery journeys has pointed to the importance of identity change processes, through which the internalised stigma and status of an ‘‘addict identity’’ is supplanted with a new identity. This theoretical paper argues that recovery is best understood as a personal journey of socially negotiated identity transition that occurs through changes in social networks and related meaningful activities. Alcoholics Anonymous (AA) is used as a case study to illustrate this process of social identity transition. In line with recent social identity theorising, it is proposed that (a) identity change in recovery is socially negotiated, (b) recovery emerges through socially mediated processes of social learning and social control and (c) recovery can be transmitted in social networks through a process of social influence

Weight change and sulfonylurea therapy are related to 3 year change in microvascular function in people with type 2 diabetes

Aims/hypothesis: Although cardiovascular disease is the biggest cause of death in people with diabetes, microvascular complications have a significant impact on quality of life and financial burden of the disease. Little is known about the progression of microvascular dysfunction in the early stages of type 2 diabetes before the occurrence of clinically apparent complications. We aimed to explore the determinants of endothelial-dependent and -independent microvascular function progression over a 3 year period, in people with and without both diabetes and few clinical microvascular complications. Methods: Demographics were collected in 154 participants with type 2 diabetes and in a further 99 participants without type 2 diabetes. Skin microvascular endothelium-dependent response to iontophoresis of acetylcholine and endothelium-independent responses to sodium nitroprusside were measured using laser Doppler fluximetry. All assessments were repeated 3 years later. Results: People with type 2 diabetes had impaired endothelial-dependent microvascular response compared with those without (AUC 93.9 [95% CI 88.1, 99.4] vs 111.9 [102.3, 121.4] arbitrary units [AU] × min, p < 0.001, for those with vs without diabetes, respectively). Similarly, endothelial-independent responses were attenuated in those with diabetes (63.2 [59.2, 67.2] vs 75.1 [67.8, 82.4] AU × min, respectively, p = 0.002). Mean microvascular function declined over 3 years in both groups to a similar degree (pinteraction 0.74 for response to acetylcholine and 0.69 for response to sodium nitroprusside). In those with diabetes, use of sulfonylurea was associated with greater decline (p = 0.022 after adjustment for co-prescriptions, change in HbA1c and weight), whereas improving glycaemic control was associated with less decline of endothelial-dependent microvascular function (p = 0.03). Otherwise, the determinants of microvascular decline were similar in those with and without diabetes. The principal determinant of change in microvascular function in the whole population was weight change over 3 years, such that those that lost ≥5% weight had very little decline in either endothelial-dependent or -independent function compared with those that were weight stable, whereas those who gained weight had a greater decline in function (change in endothelial-dependent function was 1.2 [95% CI -13.2, 15.7] AU × min in those who lost weight; -15.8 [-10.5, -21.0] AU × min in those with stable weight; and -37.8 [-19.4, -56.2] AU × min in those with weight gain; ptrend < 0.001). This association of weight change with change in endothelial function was driven by people with diabetes; in people without diabetes, the relationship was nonsignificant. Conclusions/interpretation: Over 3 years, physiological change in weight was the greatest predictor of change in microvascular function.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was supported by the Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006).published version, accepted version (12 month embargo

Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals With Type 2 Diabetes

The parameters derived from reservoir-excess pressure analysis (RPA) have prognostic utility in several populations. However, evidence in type 2 diabetes (T2DM) remains scarce. We determined if these parameters were associated with T2DM, and whether they would predict cardiovascular events in individuals with T2DM.We studied 306people with T2DM and cardiovascular disease (CVD)(DMCVD:70.4±7.8yrs), 348people with T2DM but without CVD (DM:67.7±8.4yrs) and 178peoplewithout T2DM or CVD (CTRL:67.2±8.9yrs). RPA-derived parameters including reservoir pressure integral (INTPR), peak reservoir pressure (MAXPR), excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC) were obtained by radial artery tonometry. INTPR was lower in DMCVD and DM than CTRL. MAXPR was lower, and INTXSP was greater in DMCVD than DM and CTRL. SRC was lower in a stepwise manner among groups(DMCVD&lt;DM&lt;CTRL).DRC was greater in DMCVD than CTRL. In the sub group of individuals with T2DM (n=642), 14 deaths (6 cardiovascular and 9non-cardiovascular causes) and 108cardiovascular events occurred during a 3-yr follow-up period. Logistic regression analysis revealed that INTPR [odds ratio 0.59(95%CI:0.45-0.79)] and DRC [odds ratio 1.60(95%CI:1.25-2.06)] were independent predictors of cardiovascular events during follow-up after adjusting for conventional risk factors(both p&lt;0.001). Further adjustments for potential confounders had no influence on associations. These findings demonstrate that altered RPA-derived parameters are associated with T2DM. Furthermore, baseline values of INTPR and DRC independently predict cardiovascular events in individuals with T2DM, indicating the potential clinical utility of these parameters for risk stratification in T2DM

ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling

Whereas genomic aberrations in the SLIT-ROBO pathway are frequent in pancreatic ductal adenocarcinoma (PDAC), their function in the pancreas is unclear. Here we report that in pancreatitis and PDAC mouse models, epithelial Robo2 expression is lost while Robo1 expression becomes most prominent in the stroma. Cell cultures of mice with loss of epithelial Robo2 (Pdx1 ;Robo2 ) show increased activation of Robo1 myofibroblasts and induction of TGF-β and Wnt pathways. During pancreatitis, Pdx1 ;Robo2 mice present enhanced myofibroblast activation, collagen crosslinking, T-cell infiltration and tumorigenic immune markers. The TGF-β inhibitor galunisertib suppresses these effects. In PDAC patients, ROBO2 expression is overall low while ROBO1 is variably expressed in epithelium and high in stroma. ROBO2 ;ROBO1 patients present the poorest survival. In conclusion, Robo2 acts non-autonomously as a stroma suppressor gene by restraining myofibroblast activation and T-cell infiltration. ROBO1/2 expression in PDAC patients may guide therapy with TGF-β inhibitors or other stroma /immune modulating agents

Evaluation of (−)-epicatechin metabolites as recovery biomarker of dietary flavan-3-ol intake

Abstract: Data from dietary intervention studies suggest that intake of (−)-epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide. Here, we evaluate a series of structurally related (−)-epicatechin metabolites (SREM), particularly (−)-epicatechin-3′-glucuronide, (−)-epicatechin-3′-sulfate and 3′-O-methyl-(−)-epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-epicatechin intake. SREMB in urine proved to be a specific indicator of (−)-epicatechin intake, showing also a strong correlation with the amount of (−)-epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92). The median recovery of (−)-epicatechin as SREMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L. Our results show that SREMB are suitable as biomarker of (−)-epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (−)-epicatechin