The role of GP’s compensation schemes in diabetes care: evidence from panel data

The design of incentive schemes that improve quality of care is a central issue for the healthcare sector. Nowadays we observe many pay-for-performance programs, where payment is contingent on meeting indicators of provider effort, but also other alternative strategies have been introduced, for example programs rewarding physicians for participation in diseases management plans. Although it has been recognised that incentive-based remuneration schemes can have an impact on GP behaviour, there is still weak empirical evidence on the extent to which such programs influence health outcomes. We investigate the impact of financial incentives in Regional and Local Health Authority contracts for primary care in the Italian Region Emilia Romagna for the years 2003-05. We focus on avoidable hospitalisations (Ambulatory Care Sensitive Conditions) for patients affected by type 2 diabetes mellitus, for which the assumption of responsibility and the adoption of clinical guidelines are specifically rewarded. We estimate a panel count data model using a Negative Binomial distribution to test the hypothesis that, other things equal, patients under the responsibility of GPs receiving a higher share of their income through these programs are less likely to experience avoidable hospitalisations. Our findings support the hypothesis that financial transfers may contribute to improve quality of care, even when they are not based on the ex-post verification of performances.

Enabling solid biomass fired small scale cogeneration systems with the twin screw wet steam expander technology

Distributed power generation in industrial, urban and commercial applications is a key topic for the strategic development and implementation of modern energy policies. Solid biomass fired small scale cogeneration plants can play an important role in Europe to improve environmental and economic impact of such policies. As a result of advances in the design and development of twin-screw wet steam expanders, they now appear as an efficient enabling technology for this small scale de-centralized cogeneration plants. Same as backpressure turbines, twinscrew steam expander can generate power by reducing the pressure between the steam source and the downstream steam/heat user, but with the advantage of adopting wet steam as working fluid. The paper will describe the principles of steam screw expander operation and performance characterization and discuss installations of the expander genset in various industrial and urban (district heating) applications where steam is generated with solid biomass fired saturated steam boilers

MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells

Mir-205 plays an important role in epithelial biogenesis and in mammary gland development but its role in cancer still remains controversial depending on the specific cellular context and target genes. We have previously reported that miR-205-5p is upregulated in breast cancer stem cells targeting ERBB pathway and leading to targeted therapy resistance. Here we show that miR-205-5p regulates tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer results in reduced tumor growth and metastatic spreading in mouse models. Moreover, we show that miR-205-5p knock-down can be obtained with the use of specific locked nucleic acids oligonucleotides in vivo suggesting a future potential use of this approach in therapy

A lunar space station

A concept for a space station to be placed in low lunar orbit in support of the eventual establishment of a permanent moon base is proposed. This space station would have several functions: (1) a complete support facility for the maintenance of the permanent moon base and its population; (2) an orbital docking area to facilitate the ferrying of materials and personnel to and from Earth; (3) a zero gravity factory using lunar raw materials to grow superior GaAs crystals for use in semiconductors and mass produce inexpensive fiber glass; and (4) a space garden for the benefit of the air food cycles. The mission scenario, design requirements, and technology needs and developments are included as part of the proposal

Suppression of Pdx-1 perturbs proinsulin processing, insulin secretion and GLP-1 signalling in INS-1 cells

Aims/hypothesis: Mutations in genes encoding HNF-4α, HNF-1α and IPF-1/Pdx-1 are associated with, respectively, MODY subtypes-1, -3 and -4. Impaired glucose-stimulated insulin secretion is the common primary defect of these monogenic forms of diabetes. A regulatory circuit between these three transcription factors has also been suggested. We aimed to explore how Pdx-1 regulates beta cell function and gene expression patterns. Methods: We studied two previously established INS-1 stable cell lines permitting inducible expression of, respectively, Pdx-1 and its dominant-negative mutant. We used HPLC for insulin processing, adenovirally encoded aequorin for cytosolic [Ca2+], and transient transfection of human growth hormone or patch-clamp capacitance recordings to monitor exocytosis. Results: Induction of DN-Pdx-1 resulted in defective glucose-stimulated and K+-depolarisation-induced insulin secretion in INS-1 cells, while overexpression of Pdx-1 had no effect. We found that DN-Pdx-1 caused down-regulation of fibroblast growth factor receptor 1 (FGFR1), and consequently prohormone convertases (PC-1/3 and -2). As a result, DN-Pdx-1 severely impaired proinsulin processing. In addition, induction of Pdx-1 suppressed the expression of glucagon-like peptide 1 receptor (GLP-1R), which resulted in marked reduction of both basal and GLP-1 agonist exendin-4-stimulated cellular cAMP levels. Induction of DN-Pdx-1 did not affect glucokinase activity, glycolysis, mitochondrial metabolism or ATP generation. The K+-induced cytosolic [Ca2+] rise and Ca2+-evoked exocytosis (membrane capacitance) were not abrogated. Conclusions/interpretation: The severely impaired proinsulin processing combined with decreased GLP-1R expression and cellular cAMP content, rather than metabolic defects or altered exocytosis, may contribute to the beta cell dysfunction induced by Pdx-1 deficienc

Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p < 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p < 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p < 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

Rab3D is critical for secretory granule maturation in PC12 cells.

Neuropeptide- and hormone-containing secretory granules (SGs) are synthesized at the trans-Golgi network (TGN) as immature secretory granules (ISGs) and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs). Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I) decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

Acknowledgements We wish to thank Jorge Galán, Gregory Pazour, Derek Toomre, Giuliano Callaini, Joel Rosenbaum, Alessandra Boletta and Francesco Blasi for generously providing reagents and for productive discussions, and Sonia Grassini for technical assistance. The work was carried out with the financial support of Telethon (GGP11021) and AIRC.Peer reviewedPostprin