Poly-Orogenic Melting of Metasedimentary Crust From a Granite Geochemistry and Inherited Zircon Perspective (Southern Calabria-Peloritani Orogen, Italy)

Inherited zircon ages and geochemical features of late Cadomian and late Variscan granitoids from the north-eastern Peloritani Mountains (NE Sicily) and the western Aspromonte Massif (SW Calabria) shed new light on the sources and processes involved in poly-orogenic granitoid magmatism. The two groups of strongly peraluminous granitoids have similarities in trace element abundance patterns, and Sr and Nd isotopic compositions consistent with both being derived from crustal sources, possibly with a minor contribution from mantle-related components. Comparison of the granite compositions with those of experimental melts derived from various metaigneous and metasedimentary sources indicates that both groups of granitoids originated exclusively from different degrees of melting of similar greywacke-dominated turbidite. Abundant inherited zircon cores from representative samples of metamorphosed late Cadomian (545 ± 5 Ma) granite and late Variscan (300 ± 4 Ma) leucogranodiorite have the same range of U–Pb ages, from Early Paleoproterozoic to latest Neoproterozoic, with main age clusters at ∼0.55 and ∼0.63 Ga, and minor age clusters at ∼0.95 and ∼2.5 Ga. The pattern of detrital zircon ages from a paragneiss, host rock to the late Cadomian granite, is the same, indicating, in conjunction with the geochemistry, that both granites originated by partial melting of deeper crustal equivalents of those paragneisses. The same crustal sequence melted during successive orogenies under different thermal regimes and in different post-collisional tectonic settings, giving rise to granitoid associations with different ages and geochemical features largely reflecting the melting conditions. On the other hand, the zircon inheritance patterns and specific chemical features of S-type granitoids reflect the nature of their crustal magma sources, independently from the effects of the thermal regime or tectonic setting at the time of magmatism

Quality target negotiation in health care : evidence from the English NHS

We examine how public sector third-party purchasers and hospitals negotiate quality targets when a fixed proportion of hospital revenue is required to be linked to quality. We develop a bargaining model linking the number of quality targets to purchaser and hospital characteristics. Using data extracted from 153 contracts for acute hospital services in England in 2010/11, we find that the number of quality targets is associated with the purchaser’s population health and its budget, the hospital type, whether the purchaser delegated negotiation to an agency, and the quality targets imposed by the supervising regional health authority

Data quality and practical challenges of thyroid volume assessment by ultrasound under field conditions - observer errors may affect prevalence estimates of goitre

<p>Abstract</p> <p>Background</p> <p>The ultrasonographic estimation of thyroid size has been advocated as being more precise than palpation to diagnose goitre. However, ultrasound also requires technical proficiency. This study was conducted among Saharawi refugees, where goitre is highly prevalent. The objectives were to assess the overall data quality of ultrasound measurements of thyroid volume (Tvol), including the intra- and inter-observer agreement, under field conditions, and to describe some of the practical challenges encountered.</p> <p>Methods</p> <p>In 2007 a cross-sectional study of 419 children (6-14 years old) and 405 women (15-45 years old) was performed on a population of Saharawi refugees with prevalent goitre, who reside in the Algerian desert. Tvol was measured by two trained fieldworkers using portable ultrasound equipment (examiner 1 measured 406 individuals, and examiner 2, 418 individuals). Intra- and inter-observer agreement was estimated in 12 children selected from the study population but not part of the main study. In the main study, an observer error was found in one examiner whose ultrasound images were corrected by linear regression after printing and remeasuring a sample of 272 images.</p> <p>Results</p> <p>The intra-observer agreement in Tvol was higher in examiner 1, with an intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.91, 0.99) compared to 0.86 (95% CI: 0.60, 0.96) in examiner 2. The ICC for inter-observer agreement in Tvol was 0.38 (95% CI: -0.20, 0.77). Linear regression coefficients indicated a significant scaling bias in the original measurements of the AP and ML diameter and a systematic underestimation of Tvol (a product of AP, ML, CC and a constant). The agreement between re-measured and original Tvol measured by ICC (95% CI) was 0.76 (0.71, 0.81). The agreement between re-measured and corrected Tvol measured by ICC (95% CI) was 0.97 (0.96, 0.97).</p> <p>Conclusions</p> <p>An important challenge when using ultrasound to assess thyroid volume under field conditions is to recruit and train qualified personnel to perform the measurements. Methodological studies are important to assess data quality and can facilitate statistical corrections and improved estimates.</p

Divergent mind-sets, convergent policies: Policing models against organized crime in Italy and in England within international frameworks

The fight against organized crime is a very fertile ground for policymaking at various levels. On one side, because of the perceived transnationality of the phenomenon, national states are inclined to develop harmonized responses within the European or international law frameworks. On the other side, national conceptualizations and manifestations of organized crime often make these harmonizations quite challenging. This paper shares the findings of a socio-legal investigation carried out in England and in Italy through interviews and document analysis, comparing the two national models against organized crime. The paper presents these two models ? the Italian Structure Model and the English Activity Model, which are very different in many ways ? in order to identify divergences and convergences of policies and practices. This comparative exercise not only improves our understanding of national approaches, beyond cultural, linguistic and legal boundaries, but also improves the dialogue towards concerted efforts at the international level. Nevertheless, the globalization of criminal markets and the internationalization of policies have influenced perceptions of organized crime and related policing tactics at national levels too. This paper will briefly look at international perspectives to assess to what extent divergent and convergent areas between the two models are also areas of interest and focus at the international level, in order to conclude with an enhanced understanding of both models before drawing conclusions

Inferring predominant pathways in cellular models of breast cancer using limited sample proteomic profiling

<p>Abstract</p> <p>Background</p> <p>Molecularly targeted drugs inhibit aberrant signaling within oncogenic pathways. Identifying the predominant pathways at work within a tumor is a key step towards tailoring therapies to the patient. Clinical samples pose significant challenges for proteomic profiling, an attractive approach for identifying predominant pathways. The objective of this study was to determine if information obtained from a limited sample (i.e., a single gel replicate) can provide insight into the predominant pathways in two well-characterized breast cancer models.</p> <p>Methods</p> <p>A comparative proteomic analysis of total cell lysates was obtained from two cellular models of breast cancer, BT474 (HER2+/ER+) and SKBR3 (HER2+/ER-), using two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Protein interaction networks and canonical pathways were extracted from the Ingenuity Pathway Knowledgebase (IPK) based on association with the observed pattern of differentially expressed proteins.</p> <p>Results</p> <p>Of the 304 spots that were picked, 167 protein spots were identified. A threshold of 1.5-fold was used to select 62 proteins used in the analysis. IPK analysis suggested that metabolic pathways were highly associated with protein expression in SKBR3 cells while cell motility pathways were highly associated with BT474 cells. Inferred protein networks were confirmed by observing an up-regulation of IGF-1R and profilin in BT474 and up-regulation of Ras and enolase in SKBR3 using western blot.</p> <p>Conclusion</p> <p>When interpreted in the context of prior information, our results suggest that the overall patterns of differential protein expression obtained from limited samples can still aid in clinical decision making by providing an estimate of the predominant pathways that underpin cellular phenotype.</p

Late-Proterozoic to Paleozoic history of the peri-Gondwana Calabria–Peloritani Terrane inferred from a review of zircon chronology

U–Pb analyses of zircon from ten samples of augen gneisses, eight mafic and intermediate metaigneous rocks and six metasediments from some tectonic domains along the Calabria–Peloritani Terrane (Southern Italy) contribute to knowledge of peri-Gondwanan evolution from Late-Proterozoic to Paleozoic times. All samples were equilibrated under amphibolite to granulite facies metamorphism during the Variscan orogeny. The zircon grains of all considered samples preserve a Proterozoic memory suggestive of detrital, metamorphic and igneous origin. The available data fit a frame involving: (1) Neoproterozoic detrital input from cratonic areas of Gondwana; (2) Pan-African/Cadomian assemblage of blocks derived from East and West African Craton; (3) metamorphism and bimodal magmatism between 535 and 579 Ma, within an active margin setting; (4) rifting and opening of Ordovician basins fed by detrital input from the assembled Cadomian blocks. The Paleozoic basins evolved through sedimentation, metamorphism and magmatism during the Variscan orogeny involving Palaeozoic and pre-Paleozoic blocks. The Proterozoic zircon records decidedly decrease in the high grade metamorphic rocks affected by Variscan pervasive partial melting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40064-016-1839-8) contains supplementary material, which is available to authorized users

Insulin-like growth factors and insulin control a multifunctional signalling network of significant importance in cancer

Insulin-like growth factor (IGF) and insulin (INS) proteins regulate key cellular functions through a complex interacting multi-component molecular network, known as the IGF/INS axis. We describe how dynamic and multilayer interactions give rise to the multifunctional role of the IGF/INS axis. Furthermore, we summarise the importance of the regulatory IGF/INS network in cancer, and discuss the possibilities and limitations of therapies targeting the IGF/INS axis with reference to ongoing clinical trials concerning the blockage of IGF1R in several types of cancer

Pubertal high fat diet: effects on mammary cancer development

INTRODUCTION: Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. METHODS: Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. RESULTS: HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages. CONCLUSIONS: Taken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD

The beta secretase BACE1 regulates the expression of insulin receptor in the liver

Insulin receptor (IR) plays a key role in the control of glucose homeostasis; however, the regulation of its cellular expression remains poorly understood. Here we show that the amount of biologically active IR is regulated by the cleavage of its ectodomain, by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), in a glucose concentration-dependent manner. In vivo studies demonstrate that BACE1 regulates the amount of IR and insulin signaling in the liver. During diabetes, BACE1-dependent cleavage of IR is increased and the amount of IR in the liver is reduced, whereas infusion of a BACE1 inhibitor partially restores liver IR. We suggest the potential use of BACE1 inhibitors to enhance insulin signaling during diabetes. Additionally, we show that plasma levels of cleaved IR reflect IR isoform A expression levels in liver tumors, which prompts us to propose that the measurement of circulating cleaved IR may assist hepatic cancer detection and management