Proposal for a Performance Dashboard for the Monitoringof Water and Sewage Service Companies (WaSCs)

The water and sewage industry provides an essential service to the community, but it is characterized by natural monopoly tendencies of service suppliers. In this framework, it is very important to assist regulators with a small set of critical indicators (performance dashboard) for the evaluation and monitoring of the service provided by Water and Sewage Companies (WaSCs). The paper originates from the analysis of situation of Piemonte (Italy), where each regional and local body adopts a proprietary Performance Measurement System (PMS). In order to improve the coordination of information flow and to support the definition of common service standards, a methodology to merge existing PMSs and define a unique shared reference system is proposed. The Kaplan and Norton's Balanced Scorecard (BSC) is adopted as the reference model of this approach. BSC is widely recognized to be an exhaustive and balanced framework in describing the performances of an organization and ensures that all the operational aspects of WaSCs are adequately monitored. The output of the proposed procedure is a general performance dashboard for the monitoring of WaSCs. The dashboard is shown and some remarks about indicators properties are developed. In particular, this analysis highlights some common pitfalls originated by a ‘rushed' aggregation of several performance indicators. Description is supported by several example

Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro

<p>Abstract</p> <p>Background</p> <p>In 2005, Ghana replaced chloroquine with artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. The aim of this work was to determine for the first time, polymorphisms in the putative <it>pfATPase6 </it>and <it>pftctp</it>, <it>pfmdr1</it>, <it>pfcrt </it>genes in Ghanaian isolates, particularly at a time when there is no report on artemisinin resistance in malaria parasites from Ghana. The sensitivity of parasite isolates to anti-malaria drugs were also evaluated for a possible association with polymorphisms in these genes.</p> <p>Methods</p> <p>The prevalence of point mutations in the above <it>Plasmodium falciparum </it>genes were assessed from filter-paper blood blot samples by DNA sequencing. <it>In vitro </it>drug sensitivity test was carried out on some of the blood samples from volunteers visiting hospitals/clinics in southern Ghana using a modified version of the standard WHO Mark III micro-test.</p> <p>Results</p> <p>All successfully tested parasite isolates were sensitive to artesunate; while 19.4%, 29.0% and 51.6% were resistant to quinine, amodiaquine and chloroquine respectively. The geometric mean of IC₅₀value for artesunate was 0.73 nM (95% CI, 0.38-1.08), amodiaquine 30.69 nM (95% CI, 14.18-47.20) and chloroquine 58.73 nM (95% CI, 38.08-79.38). Twenty point mutations were observed in <it>pfATPase6 </it>gene, with no L263E and S769N. All mutations found were low in frequency, except D639G which was observed in about half of the isolates but was not associated with artesunate response (<it>p </it>= 0.42). The <it>pftctp </it>gene is highly conserved as no mutation was observed, while CVIET which is chloroquine-resistant genotype at codon 72-76 of the <it>pfcrt </it>gene was identified in about half of the isolates; this was consistent with chloroquine IC₅₀values (<it>p </it>= 0.001). Mutations were present in <it>pfmdr1 </it>gene but were not associated with artemisinin response (<it>p </it>= 1.00).</p> <p>Conclusion</p> <p>The <it>pfATPase6 </it>gene is highly polymorphic with D639G appearing to be fixed in Ghanaian isolates. These may just be spontaneous mutations as all parasite isolates that were tested displayed satisfactory <it>in vitro </it>response to artesunate. However, there is no improvement in susceptibility of the parasites to chloroquine five years after its proscription.</p

Adapting “MOVE” to accelerate VMMC coverage for HIV prevention in priority populations:Implementation experiences from Uganda’s military settings

This paper describes the WHO’s Model of Optimizing Volumes and Efficiencies (MOVE), adapted by the University Research Council (URC) - Department of Defense HIV/AIDS Prevention Program (DHAPP) to rapidly scale up Voluntary Medical Male Circumcision (VMMC) within Uganda’s military health facilities. First, we examine the MOVE model and then present the URC-DHAPP adapted intervention package comprising of: a) a Command-driven approach, b) Mobile theatres c) Quality assurance d) Data strengthening and reflection. To expand VMMC, URC-DHAPP worked with army commanders to create awareness, mobilize their troops and surgeons were assigned daily targets. The mobile theatre involved regular visits to hard-to-reach outposts and placing several mobile camps at health facilities close to deployment sites. All stakeholders were briefed on performance trends of previous medical camps and the program was monitored through VMMC camp reports. URC-DHAPP registered an exponential increase in VMMC coverage from 13% performance at Q2 to over 140% in Q4. The integrated approach led to circumcision of over 22,000 men (15-49 years) in a record four months. Our approach also contributed to health system strengthening and national HIV preventiontargets. We conclude that the MOVE is cost-effective and can be successfully scaled up in resource-limited settings with a high HIV burden when implemented with cognizance of contextual specificities

Neuronal activity in medial superior temporal area (MST) during memory-based smooth pursuit eye movements in monkeys

We examined recently neuronal substrates for predictive pursuit using a memory-based smooth pursuit task that distinguishes the discharge related to memory of visual motion-direction from that related to movement preparation. We found that the supplementary eye fields (SEF) contain separate signals coding memory and assessment of visual motion-direction, decision not-to-pursue, and preparation for pursuit. Since medial superior temporal area (MST) is essential for visual motion processing and projects to SEF, we examined whether MST carried similar signals. We analyzed the discharge of 108 MSTd neurons responding to visual motion stimuli. The majority (69/108 = 64%) were also modulated during smooth pursuit. However, in nearly all (104/108 = 96%) of the MSTd neurons tested, there was no significant discharge modulation during the delay periods that required memory of visual motion-direction or preparation for smooth pursuit or not-to-pursue. Only 4 neurons of the 108 (4%) exhibited significantly higher discharge rates during the delay periods; however, their responses were non-directional and not instruction specific. Representative signals in the MSTd clearly differed from those in the SEF during memory-based smooth pursuit. MSTd neurons are unlikely to provide signals for memory of visual motion-direction or preparation for smooth pursuit eye movements

Extreme Type-II Superconductors in a Magnetic Field: A Theory of Critical Fluctuations

A theory of critical fluctuations in extreme type-II superconductors subjected to a finite but weak external magnetic field is presented. It is shown that the standard Ginzburg-Landau representation of this problem can be recast, with help of a novel mapping, as a theory of a new "superconductor", in an effective magnetic field whose overall value is zero, consisting of the original uniform field and a set of neutralizing unit fluxes attached to $N_{\Phi}$ fluctuating vortex lines. The long distance behavior is related to the anisotropic gauge theory in which the original magnetic field plays the role of "charge". The consequences of this "gauge theory" scenario for the critical behavior in high temperature superconductors are explored in detail, with particular emphasis on questions of 3D XY vs. Landau level scaling, physical nature of the vortex "line liquid" and the true normal state, and fluctuation thermodynamics and transport. A "minimal" set of requirements for the theory of vortex-lattice melting in the critical region is also proposed and discussed.Comment: 28 RevTeX pages, 4 .ps figures; appendix A added, additional references, streamlined Secs. IV and V in response to referees' comment

Topological phase-fluctuations, amplitude fluctuations, and criticality in extreme type-II superconductors

We study the effect of critical fluctuations on the $(B,T)$ phase diagram in extreme type-II superconductors in zero and finite magnetic field using large-scale Monte Carlo simulations on the Ginzburg-Landau model in a frozen gauge approximation. We show that a vortex-loop unbinding gives a correct picture of the zero field superconducting-normal transition even in the presence of amplitude fluctuations, which are far from being critical at $T_c$. We extract critical exponents of the dual model by studying the topological excitations of the original model. From the vortex-loop distribution function we extract the anomalous dimension of the dual field $\eta \simeq -0.18$, and conclude that the charged Ginzburg-Landau model and the neutral 3DXY model belong to different universality classes. We find are two distinct scaling regimes for the vortex-line lattice melting line: a high-field scaling regime and a distinct low-field 3DXY critical scaling regime. We also find indications of an abrupt change in the connectivity of the vortex-tangle in the vortex liquid along a line $T_L \geq T_M$. This is the finite field counter-part of the zero-field vortex-loop blowout. Which at low enough fields appears to coincide with $T_M$. Here, a description of the vortex system only in terms of field induced vortex lines is inadequate at and above the VLL melting temperature.Comment: 30 pages, 14 figure

MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

Impact of gastro-oesophageal reflux on microRNA expression, location and function

We have shown that miRNA expression is altered in the oesophageal squamous mucosa from individuals with gastro-oesophageal reflux and ulcerative oesophagitis. These changes in miR-143, miR-145 and miR-205 expression appear to be most pronounced in the basal layer of the oesophageal epithelium. In the context of gastro-oesophageal reflux these expression changes might influence proliferation and apoptosis and thereby regulate epithelial restoration. It is reasonable to hypothesise that they could represent early molecular events preceding the development of Barrett’s oesophagus, although proving this will require further studies as described above. Future detailed analyses of the role of these miRNAs in progression from gastro-oesophageal reflux to Barrett’s oesophagus, and then to oesophageal adenocarcinoma will be valuable, and may help in efforts to control and treat these diseases.This study was funded by a Competing Project Grant from the National Health and Medical Research Council of Australia. Cameron Smith was supported by a PROBE-NET PhD scholarship funded by a Strategic research Partnerships Grant from the Cancer Council of New South Wales

α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation

<p>Abstract</p> <p>Background</p> <p>The mangosteen fruit has a long history of medicinal use in Chinese and Ayurvedic medicine. Recently, the compound α-mangostin, which is isolated from the pericarp of the fruit, was shown to induce cell death in various types of cancer cells in <it>in vitro </it>studies. This led us to investigate the antitumor growth and antimetastatic activities of α-mangostin in an immunocompetent xenograft model of mouse metastatic mammary cancer having a p53 mutation that induces a metastatic spectrum similar to that seen in human breast cancers.</p> <p>Methods</p> <p>Mammary tumors, induced by inoculation of BALB/c mice syngeneic with metastatic BJMC3879luc2 cells, were subsequently treated with α-mangostin at 0, 10 and 20 mg/kg/day using mini-osmotic pumps and histopathologically examined. To investigate the mechanisms of antitumor ability by α-mangostin, <it>in vitro </it>studies were also conducted.</p> <p>Results</p> <p>Not only were <it>in vivo </it>survival rates significantly higher in the 20 mg/kg/day α-mangostin group versus controls, but both tumor volume and the multiplicity of lymph node metastases were significantly suppressed. Apoptotic levels were significantly increased in the mammary tumors of mice receiving 20 mg/kg/day and were associated with increased expression of active caspase-3 and -9. Other significant effects noted at this dose level were decreased microvessel density and lower numbers of dilated lymphatic vessels containing intraluminal tumor cells in mammary carcinoma tissues.</p> <p><it>In vitro</it>, α-mangostin induced mitochondria-mediated apoptosis and G1-phase arrest and S-phase suppression in the cell cycle. Since activation by Akt phosphorylation plays a central role in a variety of oncogenic processes, including cell proliferation, anti-apoptotic cell death, angiogenesis and metastasis, we also investigated alterations in Akt phosphorylation induced by α-mangostin treatment both <it>in vitro </it>and <it>in vivo</it>. Quantitative analysis and immunohistochemistry showed that α-mangostin significantly decreased the levels of phospho-Akt-threonine 308 (Thr308), but not serine 473 (Ser473), in both mammary carcinoma cell cultures and mammary carcinoma tissues <it>in vivo</it>.</p> <p>Conclusions</p> <p>Since lymph node involvement is the most important prognostic factor in breast cancer patients, the antimetastatic activity of α-mangostin as detected in mammary cancers carrying a p53 mutation in the present study may have specific clinical applications. In addition, α-mangostin may have chemopreventive benefits and/or prove useful as an adjuvant therapy, or as a complementary alternative medicine in the treatment of breast cancer.</p