Insulin receptor substrate-2 is expressed in kidney epithelium and up-regulated in diabetic nephropathy

Diabetic nephropathy (DN) is a progressive fibrotic condition that may lead to end-stage renal disease and kidney failure. Transforming growth factor-ß1 and bone morphogenetic protein-7 (BMP7) have been shown to induce DN-like changes in the kidney and protect the kidney from such changes, respectively. Recent data identified insulin action at the level of the nephron as a crucial factor in the development and progression of DN. Insulin requires a family of insulin receptor substrate (IRS) proteins for its physiological effects, and many reports have highlighted the role of insulin and IRS proteins in kidney physiology and disease. Here, we observed IRS2 expression predominantly in the developing and adult kidney epithelium in mouse and human. BMP7 treatment of human kidney proximal tubule epithelial cells (HK-2 cells) increases IRS2 transcription. In addition, BMP7 treatment of HK-2 cells induces an electrophoretic shift in IRS2 migration on SDS/PAGE, and increased association with phosphatidylinositol-3-kinase, probably due to increased tyrosine/serine phosphorylation. In a cohort of DN patients with a range of chronic kidney disease severity, IRS2 mRNA levels were elevated approximately ninefold, with the majority of IRS2 staining evident in the kidney tubules in DN patients. These data show that IRS2 is expressed in the kidney epithelium and may play a role in the downstream protective events triggered by BMP7 in the kidney. The specific up-regulation of IRS2 in the kidney tubules of DN patients also indicates a novel role for IRS2 as a marker and/or mediator of human DN progression.

Digging up the future

Malone, C. and S. Stoddart,. , in Nonesuch - magazine of University of Bristol. 1995, University of Bristol: Bristol. p. 40-42.

Voices from higher up the ladder:Exploring the team leader role in call centres

This paper focuses on an under-researched employee category in the call centre literature-the team leader. The paper, drawing on data from nine Australian call centres, finds that the team leader role is integral to the effectiveness of call centres, yet it is a role that consists of considerable complexity and contradictions. The research demonstrates the critical role performed by team leaders: coach, mentor, trainer, performance evaluator, communicator and supervisor. It also shows team leaders as being far more positive about many of the features of the call centre work environment compared with those on the front line. However, there does appear to be a need for greater acknowledgement of their challenging role, the contradictions that are inherent in the job and the need, in many cases, for increased support being made available to assist. © 2013 John Wiley & Sons Ltd.

Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes

From our linkage study of Irish families with a high density of schizophrenia, we have previously reported evidence for susceptibility genes in regions 5q21-31, 6p24-21, 8p22-21, and 10p15-p11. In this report, we describe the cumulative results from independent genome scans of three a priori random subsets of 90 families each, and from multipoint analysis of all 270 families in ten regions. Of these ten regions, three (13q32, 18p11-q11, and 18q22-23) did not generate scores above the empirical baseline pairwise scan results, and one (6q13-26) generated a weak signal. Six other regions produced more positive pairwise and multipoint results. They showed the following maximum multipoint H-LOD (heterogeneity LOD) and NPL scores: 2p14-13: 0.89 (P = 0.06) and 2.08 (P = 0.02), 4q24-32: 1.84 (P = 0.007) and 1.67 (P = 0.03), 5q21-31: 2.88 (P= 0.0007), and 2.65 (P = 0.002), 6p25-24: 2.13 (P = 0.005) and 3.59 (P = 0.0005), 6p23: 2.42 (P = 0.001) and 3.07 (P = 0.001), 8p22-21: 1.57 (P = 0.01) and 2.56 (P = 0.005), 10p15-11: 2.04 (P = 0.005) and 1.78 (P = 0.03). The degree of 'internal replication' across subsets differed, with 5q, 6p, and 8p being most consistent and 2p and 10p being least consistent. On 6p, the data suggested the presence of two susceptibility genes, in 6p25-24 and 6p23-22. Very few families were positive on more than one region, and little correlation between regions was evident, suggesting substantial locus heterogeneity. The levels of statistical significance were modest, as expected from loci contributing to complex traits. However, our internal replications, when considered along with the positive results obtained in multiple other samples, suggests that most of these six regions are likely to contain genes that influence liability to schizophrenia.

Predictions of survival up to 10 years after diagnosis for European women with breast cancer in 2000-2002

Few studies have addressed longer-term survival for breast cancer in European women. We have made predictions of 10-year survival for European women diagnosed with breast cancer in 2000-2002. Data for 114,312 adult women (15-99 years) diagnosed with a first primary malignant cancer of the breast during 2000-2002 were collected in the EUROCARE-4 study from 24 population-based cancer registries in 14 European countries. We estimated relative survival at 1, 5, and 10 years after diagnosis for women who were alive at some point during 2000-2002, using the period approach. We also estimated 10-year survival conditional on survival to 1 and 5 years after diagnosis. Ten-year survival exceeded 70% in most regions, but was only 54% in Eastern Europe, with the highest value in Northern Europe (about 75%). Ten-year survival conditional on survival for 1 year was 2-6% higher than 10-year survival in all European regions, and geographic differences were smaller. Ten-year survival for women who survived at least 5 years was 88% overall, with the lowest figure in Eastern Europe (79%) and the highest in the UK (91%). Women aged 50-69 years had higher overall survival than older and younger women (79%). Six cancer registries had adequate information on stage at diagnosis; in these jurisdictions, 10-year survival was 89% for local, 62% for regional and 10% for metastatic disease. Data on stage are not collected routinely or consistently, yet these data are essential for meaningful comparison of population-based survival, which provides vital information for improving breast cancer control. What's new? Policy-makers and health-care planners need accurate data on long-term survival to improve cancer control. This Europe-wide study of 10-year survival identified low survival in Eastern Europe for women with breast cancer in 2000-2002, and wide variation by age at diagnosis. Data on stage at diagnosis are crucial for meaningful comparison of population-based survival, and fundamental for improving breast cancer control, but our analyses confirmed that stage data are not collected routinely or consistently Copyright © 2012 UICC.

Acceleration of ions up to 20MeV/nucleon in the ultrashort, high-intensity regime

The measurements reported here provide scaling laws for the ion acceleration process in the regime of ultrashort (50 fs), ultrahigh contrast (10) and ultrahigh intensity (> 10W/cm ), never investigated previously. The scaling of the accelerated ion energies was studied by varying a number of parameters such as target thickness (down to 10nm), target material (C and Al) and laser light polar- ization (circular and linear) at 35° and normal laser incidence. A twofold increase in proton energy and an order of magnitude enhancement in ion flux have been observed over the investigated thickness range at 35° angle of incidence. Further- more, at normal laser incidence, measured peak proton energies of about 20 MeV are observed almost independently of the target thickness over a wide range (50nm- 10 µm). 1. © 2012 by Società Italiana di Fisica.

Picking up the Pieces: Self-Healing in reconfigurable networks

We consider the problem of self-healing in networks that are reconfigurable in the sense that they can change their topology during an attack. Our goal is to maintain connectivity in these networks, even in the presence of repeated adversarial node deletion, by carefully adding edges after each attack. We present a new algorithm, DASH, that provably ensures that: 1) the network stays connected even if an adversary deletes up to all nodes in the network; and 2) no node ever increases its degree by more than 2 log n, where n is the number of nodes initially in the network. DASH is fully distributed; adds new edges only among neighbors of deleted nodes; and has average latency and bandwidth costs that are at most logarithmic in n. DASH has these properties irrespective of the topology of the initial network, and is thus orthogonal and complementary to traditional topology- based approaches to defending against attack. We also prove lower-bounds showing that DASH is asymptotically optimal in terms of minimizing maximum degree increase over multiple attacks. Finally, we present empirical results on power-law graphs that show that DASH performs well in practice, and that it significantly outperforms naive algorithms in reducing maximum degree increase.

Fetal Umbilical Artery Doppler Pulsatility Index as a Predictor of Cardiovascular Risk Factors in Children - A Long-Term Follow Up Study

Abstract Objective To determine if high umbilical artery Doppler (UAD) pulsatility index (PI) is associated with cardio-vascular (CV) risk-factors in children at age 12 years. Methods We studied 195 children at age 12 years who had had in-utero UAD studies performed at 28 weeks gestation. The children were grouped according to whether their umbilical Doppler PI was high (indicating poor feto-placental circulation) or normal. At age 12 years we assessed CV risk factors, including anthropometric measures, blood pressure, pulse wave velocity (a measure of arterial compliance), cardio-respiratory fitness and homocysteine and cholesterol serum levels. Results Compared with children with a normal UAD PI (N=88), the children (N=107) with high UAD PI had higher resting pulse rate (p=0.04), higher pulse wave velocity (p=0.046), higher serum homocysteine levels (p=0.032) and reduced arterial compliance (7.58 v 8.50 m/sec, p=0.029) using univariate analysis. These differences were not present when adjusting for cofounders was modelled. Conclusion High PI on UAD testing in-utero may be associated with increased likelihood of some cardio-vascular risk factors at age 12-years but confounding variables may be as important. Our study raises possible long-term benefits of in-utero UAD measurements.

Multi-Dimensional Deprivation in Ireland Among 9-Year-Olds in Ireland:An Analysis of the Growing Up in Ireland Survey’

In this paper we make use of the 9-year old wave of the Growing Up in Ireland study to analyse multidimensional deprivation in Ireland. The Alkire and Foster adjusted head count ratio approach (AHCR; 2007, 2011a, 2011b) applied here constitutes a significant improvement on union and intersection approaches and allows for the decomposition of multidimensional poverty in terms of dimensions and sub-groups. The approach involves a censoring of data such that deprivations count only for those above the specified multidimensional threshold leading to a stronger set of interrelationships between deprivation dimensions. Our analysis shows that the composition of the adjusted head ratio is influenced by a range of socio-economic factors. For less-favoured socio-economic groups dimensions relating to material deprivation are disproportionately represented while for the more advantaged groups, those relating to behavioral and emotional issues and social interaction play a greater role. Notwithstanding such variation in composition, our analysis showed that the AHCR varied systematically across categories of household type, and the social class, education and age group of the primary care giver. Furthermore, these variables combined in a cumulative manner. The most systematic variation was in relation to the head count of those above the multidimensional threshold rather than intensity, conditional on being above that cut-off point. Without seeking to arbitrate on the relative value of composite indices versus disaggregated profiles, our analysis demonstrates that there is much to be gained from adopting an approach with clearly understood axiomatic properties. Doing so allows one to evaluate the consequences of the measurement strategy employed for the understanding of levels of multidimensional deprivation, the nature of such deprivation profiles and socio-economic risk patterns. Ultimately it permits an informed assessment of the strengths and weaknesses of the particular choices made.