Lanreotide extended-release aqueous-gel formulation, injected by patient, partner or healthcare provider in patients with acromegaly in the United States: 1-year data from the SODA registry

Lanreotide depot (LD; commercial name Somatuline® Depot) is an injectable, extended-release formulation of the synthetic somatostatin analog (SSA) lanreotide. In recent clinical trials, LD was found to be suitable for self or partner administration, avoiding the need to travel to a medical facility. The Somatuline® Depot for Acromegaly (SODA) study is an ongoing, multicenter, observational study in the US investigating the efficacy, safety, convenience and symptom relief provided by LD in patients with acromegaly. Sub-analyses explore outcomes according to who administered the injection: patient, partner, healthcare provider (HCP) or a combination. Data reported here reflect one year of patient experience. Patients are eligible for inclusion if they have a diagnosis of acromegaly, are treated with LD and can give signed informed consent. Baseline data include patient demographics, previous acromegaly treatment and investigations, GH and IGF-I levels, LD dose and dose adjustment frequency. Symptom frequency, injection pain and treatment convenience are assessed using patient-reported questionnaires. As of 18 April 2012, 166 patients had enrolled in SODA. Most (72 %) achieved normal IGF-I levels after 12 months of LD treatment. Disease control was similar in self or partner injectors and in patients who received injections from their HCP, although self or partner injecting was deemed more convenient. LD was well-tolerated irrespective of who performed the injection. Self injection led to more injection-site reactions, but this did not increase the rate of treatment interruption. Acromegaly symptoms remained stable. Biochemical, safety and convenience data support the clinical validity of injecting LD at home

Symmetry breaking from Scherk-Schwarz compactification

We analyze the classical stable configurations of an extra-dimensional gauge theory, in which the extra dimensions are compactified on a torus. Depending on the particular choice of gauge group and the number of extra dimensions, the classical vacua compatible with four-dimensional Poincar\'e invariance and zero instanton number may have zero energy. For SU(N) on a two-dimensional torus, we find and catalogue all possible degenerate zero-energy stable configurations in terms of continuous or discrete parameters, for the case of trivial or non-trivial 't Hooft non-abelian flux, respectively. We then describe the residual symmetries of each vacua.Comment: 24 pages, 1 figure, Section 4 modifie

Minimal gauge-Higgs unification with a flavour symmetry

We show that a flavour symmetry a la Froggatt-Nielsen can be naturally incorporated in models with gauge-Higgs unification, by exploiting the heavy fermions that are anyhow needed to realize realistic Yukawa couplings. The case of the minimal five-dimensional model, in which the SU(2)_L x U(1)_Y electroweak group is enlarged to an SU(3)_W group, and then broken to U(1)_em by the combination of an orbifold projection and a Scherk-Schwarz twist, is studied in detail. We show that the minimal way of incorporating a U(1)_F flavour symmetry is to enlarge it to an SU(2)_F group, which is then completely broken by the same orbifold projection and Scherk-Schwarz twist. The general features of this construction, where ordinary fermions live on the branes defined by the orbifold fixed-points and messenger fermions live in the bulk, are compared to those of ordinary four-dimensional flavour models, and some explicit examples are constructed.Comment: LaTex, 37 pages, 2 figures; some clarifying comments and a few references adde

An integrated approach shows different use of water resources from Mediterranean maquis species in a coastal dune ecosystem

An integrated approach has been used to analyse the dependence of three Mediterranean species, A. unedo L., Q. ilex L., and P. latifolia L. co-occurring in a coastal dune ecosystem on two different water resources: groundwater and rainfed upper soil layers. The approach included leaf level gas exchanges, sap flow measurements and structural adaptations between 15 May and 31 July 2007. During this period it was possible to capture different species-specific response patterns to an environment characterized by a sandy soil, with a low water retention capacity, and the presence of a water table. The latter did not completely prevent the development of a drought response and, combined with previous studies in the same area, response differences between species have been partially attributed to different root distributions. Sap flow of A. unedo decreased rapidly with the decline of soil water content, while that of Q. ilex decreased only moderately. Midday leaf water potential of P. latifolia and A. unedo ranged between 122.2 and 122.7MPa throughout the measuring period, while in Q. ilex it decreased down to 123.4MPa at the end of the season. A. unedo was the only species that responded to drought with a decrease of its leaf area to sapwood area ratio from 23.9\ub11.2 (May) to 15.2\ub11.5 (July). While A. unedo also underwent an almost stepwise loss on hydraulic conductivity, such a loss did not occur for Q. ilex, whereas P. latifolia was able to slightly increase its hydraulic conducitivity. These differences show how different plant compartments coordinate differently between species in their responses to drought. The different responses appear to be mediated by different root distributions of the species and their relative resistances to drought are likely to depend on the duration of the periods in which water remains extractable in the upper soil layers

Wild Food:Plants, Fish and Small Animals on the Menu for Early Holocene Populations at al-Khiday, Central Sudan

Al Khiday, located on the bank of the White Nile in Sudan, offers an exceptionally preserved stratigraphic sequence, providing a unique opportunity to use organic residue analysis to investigate diet and subsistence over the full course of the Khartoum Mesolithic together with possible continuity or change into the Early Neolithic, a period of nearly 3000 years (8900-6000 cal BP). Whilst the vast and diverse Mesolithic fish assemblage indicates a strong reliance on products from aquatic habitats, floodplains, vegetated marshes and open water, results from the lipid residue analysis suggest that the fish were not cooked in the pots, likely being consumed in other ways. Rather, pots were more specialised in processing plants, wild grasses, leafy plants and sedges, confirmed by experimental analysis, and for the first time, providing direct chemical evidence for plant exploitation in the Khartoum Mesolithic. Non-ruminant fauna, such as warthog and low lipid-yielding reptiles such as Adanson’s mud turtle and Nile monitor lizard, which were found in significant numbers at al-Khiday, were also cooked in pots. There is little evidence for the processing of wild ruminants in the pots, suggesting either that ruminant species were not routinely hunted, or, that large wild fauna may have been cooked in different ways, possibly grilled over fires. These data suggest sophisticated economic strategies by sedentary people likely exploiting their ecological niche to the fullest. Pottery use changes considerably in the Early Neolithic, with ruminant products being more routinely processed in pots, and while the exploitation of domesticates cannot be confirmed by a small faunal assemblage, some dairying does take place. In summary, our results provide valuable information on Early and Middle Holocene lifeways in central Sudan

Mammary gland tumor promotion by chronic administration of IGF1 and the insulin analogue AspB10 in the p53R270H/⁺WAPCre mouse model

Insulin analogues are structurally modified molecules with altered pharmaco-kinetic and -dynamic properties compared to regular human insulin used by diabetic patients. While these compounds are tested for undesired mitogenic effects, an epidemiological discussion is ongoing regarding an association between insulin analogue therapy and increased cancer incidence, including breast cancer. Standard in vivo rodent carcinogenesis assays do not pick up this possible increased carcinogenic potential. Here we studied the role of insulin analogues in breast cancer development. For this we used the human relevant mammary gland specific p53R270H/⁺WAPCre mouse model. Animals received life long repeated treatment with four different insulin (-like) molecules: normal insulin, insulin glargine, insulin X10 (AspB10) or insulin-like growth factor 1 (IGF1). Insulin-like molecules with strong mitogenic signaling, insulin X10 and IGF1, significantly decreased the time for tumor development. Yet, insulin glargine and normal insulin, did not significantly decrease the latency time for (mammary gland) tumor development. The majority of tumors had an epithelial to mesenchymal transition phenotype (EMT), irrespective of treatment condition. Enhanced extracellular signaling related kinase (Erk) or serine/threonine kinase (Akt) mitogenic signaling was in particular present in tumors from the insulin X10 and IGF1 treatment groups. These data indicate that insulin-like molecules with enhanced mitogenic signaling increase the risk of breast cancer development. Moreover, the use of a tissue specific cancer model, like the p53R270H/⁺WAPCre mouse model, is relevant to assess the intrinsic pro-carcinogenic potential of mitogenic and non-mitogenic biologicals such as insulin analogues. INTRODUCTION METHODS RESULTS CONCLUSION

Riflettanza di superfici vulcaniche:la campagna 2003 sul Monte Etna

The results obtained in Mt. Etna spectroradiometric field survey of June 2003 are presented and discussed. The goal of the survey was the analysis of the reflectance properties of the young pyroclastic deposits produced after the effusive activity of 2002-2003 and of the older lava flows. To achieve this goal, a template was created in order to organize the field data collected in a number of selected sites characterised by different surface materials. The results show that reflectance of pyroclastic flows is always very low and constant, besides grain size and composition of the flow. Pahoehoe units show higher reflectance values, even though the spectral characterisation of the older lava flows must take into account weathering products and vegetation coverage

The Protein Arginine Methyltransferases 1 and 5 affect Myc properties in glioblastoma stem cells

Protein Arginine (R) methylation is the most common post-translational methylation in mammalian cells. Protein Arginine Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically and symmetrically, respectively. They are ubiquitously expressed and play fundamental roles in tumour malignancies, including glioblastoma multiforme (GBM) which presents largely deregulated Myc activity. Previously, we demonstrated that PRMT5 associates with Myc in GBM cells, modulating, at least in part, its transcriptional properties. Here we show that Myc/PRMT5 protein complex includes PRMT1, in both HEK293T and glioblastoma stem cells (GSCs). We demonstrate that Myc is both asymmetrically and symmetrically dimethylated by PRMT1 and PRMT5, respectively, and that these modifications differentially regulate its stability. Moreover, we show that the ratio between symmetrically and asymmetrically dimethylated Myc changes in GSCs grown in stem versus differentiating conditions. Finally, both PRMT1 and PRMT5 activity modulate Myc binding at its specific target promoters. To our knowledge, this is the first work reporting R asymmetrical and symmetrical dimethylation as novel Myc post-translational modifications, with different functional properties. This opens a completely unexplored field of investigation in Myc biology and suggests symmetrically dimethylated Myc species as novel diagnostic and prognostic markers and druggable therapeutic targets for GBM