The influence of comorbidity on the risk of access-related bacteremia in chronic hemodialysis patients.

Access-related bacteremia is an important cause of morbidity in chronic hemodialysis patients. The incidence of bacteremia is higher in patients dialyzing through a tunneled central venous catheter (TCVC) compared with an arteriovenous fistula (AVF). Our aim was to explore if this is explained by patient comorbidity. Two groups of chronic hemodialysis outpatients were compared: all patients who dialyzed through a TCVC at any time during 2003 and were fit enough to subsequently have a functioning AVF or renal transplant even if it was after 2003 (Group 1; n=93); and all patients who dialyzed through a TCVC in 2003 and were not fit enough to have a functioning AVF or renal transplant (Group 2; n=119). Episodes of bacteremia (n=71) were identified and those not related to access were excluded. Patients in Group 1 were younger than Group 2 (57.5 years vs. 64.8 years; P=0.001). The incidences of bacteremia in Groups 1 and 2 were, respectively, 0.31 and 0.44 episodes per 1000 patient days while dialyzing through an AVF (P=0.77), and 2.21 and 2.27 per 1000 days while dialyzing through a TCVC (P=0.91). The 3-year actual survival from January 1, 2003 to January 1, 2006 was significantly higher in Group 1 than in Group 2 (80.6% vs. 26.1%; P<0.0001) confirming the higher comorbidity of the patients in Group 2. Patients dialyzing through a TCVC (compared with an AVF) have a significantly higher risk of access-related bacteremia, irrespective of comorbidity.

Studying administrative reforms through textual analysis: the case of Italian central government accounting

This paper contributes to the literature on public-sector reforms by proposing textual analysis as a useful research strategy to explore how reform archetypes and related ideas are deployed in the parliamentary debate and regulations advancing reforms. Public Administration (PA) (Wilson 1887; Weber 1922), New Public Management (NPM) (Hood 1991, 1995; Dunleavy and Hood 1994; Ferlie et al. 1996) and Public Governance (GOV) (Osborne 2010; Rhodes 1997) can be depicted as three different archetypes providing characteristic administrative ideas and concepts (i.e. interpretive schemes) and related tools and practices (i.e. structures and systems) which lead reforms. We use textual analysis to look into more than twenty years of Italian central government accounting reforms and investigate how the three administrative archetypes have evolved, intertwined and replaced each other. Textual analysis proves a useful tool to investigate reform processes and allows highlighting that in neo-Weberian countries, such as Italy, NPM and GOV, far from being revolutionary paradigms, may represent fashionable trends that did not leave significant traces in the practice and rhetoric of reforms. These results also suggest interesting implications for practitioners and policy makers.

The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis

The androgen receptor (AR) is a key regulator of prostate growth and the principal drug target for the treatment of prostate cancer. Previous studies have mapped AR targets and identified some candidates which may contribute to cancer progression, but did not characterize AR biology in an integrated manner. In this study, we took an interdisciplinary approach, integrating detailed genomic studies with metabolomic profiling and identify an anabolic transcriptional network involving AR as the core regulator. Restricting flux through anabolic pathways is an attractive approach to deprive tumours of the building blocks needed to sustain tumour growth. Therefore, we searched for targets of the AR that may contribute to these anabolic processes and could be amenable to therapeutic intervention by virtue of differential expression in prostate tumours. This highlighted calcium/calmodulin-dependent protein kinase kinase 2, which we show is overexpressed in prostate cancer and regulates cancer cell growth via its unexpected role as a hormone-dependent modulator of anabolic metabolism. In conclusion, it is possible to progress from transcriptional studies to a promising therapeutic target by taking an unbiased interdisciplinary approach.

Intersectin is a negative regulator of dynamin recruitment to the synaptic endocytic zone in the central synapse

Intersectin is a multidomain dynamin-binding protein implicated in numerous functions in the nervous system, including synapse formation and endocytosis. Here, we demonstrate that during neurotransmitter release in the central synapse, intersectin, like its binding partner dynamin, is redistributed from the synaptic vesicle pool to the periactive zone. Acute perturbation of the intersectin-dynamin interaction by microinjection of either intersectin antibodies or Src homology 3 (SH3) domains inhibited endocytosis at the fission step. Although the morphological effects induced by the different reagents were similar, antibody injections resulted in a dramatic increase in dynamin immunoreactivity around coated pits and at constricted necks, whereas synapses microinjected with the GST (glutathione S-transferase)-SH3C domain displayed reduced amounts of dynamin in the neck region. Our data suggest that intersectin controls the amount of dynamin released from the synaptic vesicle cluster to the periactive zone and that it may regulate fission of clathrin-coated intermediates.

Central-Tapped Node Linked Modular Fault-Tolerance Topology for SRM Applications

Electric vehicles (EVs) and hybrid electric vehicles (HEVs) can reduce greenhouse gas emissions while switched reluctance motor (SRM) is one of the promising motor for such applications. This paper presents a novel SRM fault-diagnosis and fault-tolerance operation solution. Based on the traditional asymmetric half-bridge topology for the SRM driving, the central tapped winding of the SRM in modular half-bridge configuration are introduced to provide fault-diagnosis and fault-tolerance functions, which are set idle in normal conditions. The fault diagnosis can be achieved by detecting the characteristic of the excitation and demagnetization currents. An SRM fault-tolerance operation strategy is also realized by the proposed topology, which compensates for the missing phase torque under the open-circuit fault, and reduces the unbalanced phase current under the short-circuit fault due to the uncontrolled faulty phase. Furthermore, the current sensor placement strategy is also discussed to give two placement methods for low cost or modular structure. Simulation results in MATLAB/Simulink and experiments on a 750-W SRM validate the effectiveness of the proposed strategy, which may have significant implications and improve the reliability of EVs/HEVs.

Justifying accounting change through global discourses and legitimation strategies. The case of the UK central government.

Accounting has been viewed, especially through the lens of the recent managerial reforms, as a neutral technology that, in the hands of rational managers, can support effective and efficient decision making. However, the introduction of new accounting practices can be framed in a variety of ways, from value-neutral procedures to ideologically-charged instruments. Focusing on financial accounting, budgeting and performance management changes in the UK central government, and through extensive textual analysis and interviews in three government departments, this paper investigates: how accounting changes are discussed and introduced at the political level through the use of global discourses; and what strategies organisational actors subsequently use to talk about and legitimate such discourses at different organisational levels. The results shows that in political discussions there is a consistency between the discourses (largely NPM) and the accounting-related changes that took place. The research suggests that a cocktail of legitimation strategies was used by organisational actors to construct a sense of the changes, with authorisation, often in combination with, at the very least, rationalisation strategies most widely utilised. While previous literature posits that different actors tend to use the same rhetorical sequences during periods of change, this study highlights differences at different organisational levels.