453 research outputs found
Modern public internal control systems and accountability in health care organizations
The introduction of NPM principles changed the meaning and the contents of public sector accountability as it is
no longer intended as a mere compliance with rules and procedures but as the need to give an account to the citizenry,
in terms of how results are achieved and resources are used in their pursuit. Accountability for results requires
the modernisation of traditional control systems. These check whether regulations are followed without
ensuring that the achievement of objectives is controlled. Confirming the growing need in modernizing internal
control systems and increasing managerial accountability and transparency in spending public money, the European
Commission has developed a reference model for the public sector: Public Internal Financial Control –
PIfC.
The paper tries to contribute the relevant debate on the usefulness of internal control systems by exploring the
implicit positive relationship between them and managerial accountability envisaged in the PIfC model. To this
end the research focuses on a case study set in the context of Italian health care sector and in the main health care
organization located in the Region of Sardinia
Quality of Government and Well-being: An Empirical Analysis of 158 European Regions
The aim of the study is twofold: on the one hand, it assesses the association between well-being and the quality of government, on the other it evaluates the impact exerted on the same well-being by the different components into which the quality of government can be broken down. The analysis is conducted at the regional level. A
composite indicator derived from OECD data on regional well-being is used to assess its association with the quality of government. The latter is measured using the European Quality of Government Survey Index (EQI) data. The EQI breaks down the quality of government into three key elements: the impartiality of administration, the quality of services provided and the degree of corruption. The association between well-being and quality of government is verified considering, at first, the EQI index as a whole, being the product of the three different components, and then separately considering its key elements.The results confirmed the existence of a strong positive association between well-being and the overall quality of
government, as between the former and the single components of the EQI index. Furthermore, the same
association is observed when the assessment is made on the whole sample, but also when subsamples are made,
considering the geographical macro-area to which the regions belong
La digitalizzazione a supporto del processo di implementazione del nuovo modello di assistenza territoriale della ASL di Sassari
L’emergenza pandemica ha accelerato l’adozione delle tecnologie digitali e il potenziamento dell’assistenza territoriale. Il contributo analizza come la ASL di Sassari stia gestendo il processo di digitalizzazione e innovazione dei servizi territoriali, sulla spinta del PNRR e secondo i criteri del DM 77/2022 e delle direttive regionali. Il caso studio è particolarmente rilevante in quanto l’azienda è chiamata a gestire massicci investimenti e profondi cambiamenti di sistema, all’interno di una fase estremamente complessa, derivante dalla riforma regionale in atto e dal conseguente disallineamento dei processi istituzionali, organizzativi e tecnologici. Il lavoro evidenzia come la ASL di Sassari si trovi davanti a una duplice sfida: implementare in modo efficace e rapido le strategie del PNRR, secondo un approccio top-down; sviluppare dal basso l’innovazione dei servizi territoriali collegati all’uso delle nuove tecnologie digitali e al nuovo modello di medicina di prossimità .The pandemic emergency has accelerated the adoption of digital technologies and the innovation of territorial assistance. The paper explores how the Sassari Health Care Organization (HCO) is managing the digitalization and community care reorganizational process, according to the Ministerial Decree 77/2022 criteria and regional directives. In the light of recent Sardinia health care system reform, Sassari HCO represents a relevant example of how the organization is called to manage the PNRR funds within an extremely complex context, deriving from the misalignment of institutional, organizational and technological processes. The case study highlights how Sassari HCO is facing with a double challenge: implementing effectively and quickly the PNRR strategic investments, according to top-down boost; developing, through a bottom-up approach, the innovation of its health services linked to new digital technologies and primary care design
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Photodynamic therapy plus regulatory T-cell depletion produces immunity against a mouse tumour that expresses a self-antigen
Background: Photodynamic therapy (PDT) can lead to development of antigen-specific immune response and PDT-mediated immunity can be potentiated by T regulatory cell (Treg) depletion. We investigated whether the combination of PDT with cyclophosphamide (CY) could foster immunity against wild-type tumours expressing self-antigen (gp70). Methods: Mice with CT26 tumours were treated with PDT alone or in combination with low-dose CY. T regulatory cell numbers and transforming growth factor-β (TGF-β) levels were measured at several time points after treatment. Mice cured by PDT+CY were rechallenged with CT26 and monitored for long-term survival. Results: Photodynamic therapy+CY led to complete tumour regression and long-term survival in 90% of treated mice while the absolute numbers of Treg decreased after PDT+CY and the TGF-β levels were reduced to a level comparable to naïve mice. Sixty-five percent of the mice treated with PDT+CY that survived over 90 days tumour free rejected the rechallenge with the same tumour when a second dose of CY was administered before rechallenge but not without. Conclusion: Administration of CY before PDT led to depletion of Treg and potentiated PDT-mediated immunity, leading to long-term survival and development of memory immunity that was only uncovered by second Treg depletion
Osteocytic connexin 43 is not required for the increase in bone mass induced by intermittent PTH administration in male mice
Objective: To investigate whether osteocytic connexin 43 (Cx43) is required for the bone response to intermittent PTH administration, and whether the connexin is involved in maintaining the bone matrix. Methods: Human PTH(1-34) was injected to adult male mice expressing (Cx43fl/fl) or not osteocytic Cx43 (Cx43fl/fl;DMP1-8kb-Cre) daily (100 μg/kg/d) for 14 days. Results: Cx43fl/fl;DMP1-8kb-Cre mice have no difference in body weight and BMD from 1 to 4 months of age. Intermittent PTH administration increased BMD and BV/TV and induced a similar increase in type I collagen, alkaline phosphatase, runx2, osteocalcin, and bone sialoprotein expression in mice from both genotypes. On the other hand, osteocytic deletion of Cx43 did not alter mRNA levels of glycosaminoglycans, proteoglycans, collagens and osteoblast-related genes. In addition, expression of collagens assessed by immunohistochemistry was not affected by deleting osteocytic Cx43. However, PTH administration increased type II collagen only in Cx43fl/fl control mice, whereas hormone increased type I collagen expression only in Cx43fl/fl;DMP1-8kb-Cre mice. Furthermore, PTH increased maturity of collagen fibers in control, but not in Cx43-deficient mice. Conclusion: Expression of Cx43 in osteocytes is dispensable for bone anabolism induced by intermittent PTH administration; but it can modulate, at least in part, the effect of PTH on the bone matrix environment
RK-TBA studies at the RTA test facility
Construction of a prototype RF power source based on the RK-TBA concept, called the RTA, has commenced at the Lawrence Berkeley National Laboratory. This prototype will be used to study physics, engineering, and costing issues involved in the application of the RK-TBA concept to linear colliders. The status of the prototype is presented, specifically the 1-MV, 1.2-kA induction electron gun and the pulsed power system that are in assembly. The RTA program theoretical effort, in addition to supporting the development of the prototype, has been studying optimization parameters for the application of the RK-TBA concept to higher-energy linear colliders. An overview of this work is presented. 1 fig
A two-tier bioinformatic pipeline to develop probes for target capture of nuclear loci with applications in Melastomataceae
Putatively single-copy nuclear (SCN) loci, which are identified using genomic resources of closely related species, are ideal for phylogenomic inference. However, suitable genomic resources are not available for many clades, including Melastomataceae. We introduce a versatile approach to identify SCN loci for clades with few genomic resources and use it to develop probes for target enrichment in the distantly related Memecylon and Tibouchina (Melastomataceae)
Kruppel-like factor 8 regulates triple negative breast cancer stem cell-like activity
IntroductionBreast tumor development is regulated by a sub-population of breast cancer cells, termed cancer stem-like cells (CSC), which are capable of self-renewing and differentiating, and are involved in promoting breast cancer invasion, metastasis, drug resistance and relapse. CSCs are highly adaptable, capable of reprogramming their own metabolism and signaling activity in response to stimuli within the tumor microenvironment. Recently, the nutrient sensor O-GlcNAc transferase (OGT) and O-GlcNAcylation was shown to be enriched in CSC populations, where it promotes the stemness and tumorigenesis of breast cancer cells in vitro and in vivo. This enrichment was associated with upregulation of the transcription factor Kruppel-like-factor 8 (KLF8) suggesting a potential role of KLF8 in regulating CSCs properties.MethodsTriple-negative breast cancer cells were genetically modified to generate KLF8 overexpressing or KLF8 knock-down cells. Cancer cells, control or with altered KLF8 expression were analyzed to assess mammosphere formation efficiency, CSCs frequency and expression of CSCs factors. Tumor growth in vivo of control or KLF8 knock-down cells was assessed by fat-pad injection of these cell in immunocompromised mice.ResultsHere, we show that KLF8 is required and sufficient for regulating CSC phenotypes and regulating transcription factors SOX2, NANOG, OCT4 and c-MYC. KLF8 levels are associated with chemoresistance in triple negative breast cancer patients and overexpression in breast cancer cells increased paclitaxel resistance. KLF8 and OGT co-regulate each other to form a feed-forward loop to promote CSCs phenotype and mammosphere formation of breast cancer cells.DiscussionThese results suggest a critical role of KLF8 and OGT in promoting CSCs and cancer progression, that may serve as potential targets for developing strategy to target CSCs specifically
Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation
Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism
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