Dark Matter Halo Environment for Primordial Star Formation

We study the statistical properties (such as shape and spin) of high-z halos likely hosting the first (PopIII) stars with cosmological simulations including detailed gas physics. In the redshift range considered ($11 < z < 16$) the average sphericity is $= 0.3 \pm 0.1$, and for more than 90% of halos the triaxiality parameter is $T \lesssim 0.4$, showing a clear preference for oblateness over prolateness. Larger halos in the simulation tend to be both more spherical and prolate: we find $s \propto M_h^{\alpha_s}$ and $T \propto M_h^{\alpha_T}$, with $\alpha_s \approx 0.128$ and $\alpha_T= 0.276$ at z = 11. The spin distributions of dark matter and gas are considerably different at $z=16$, with the baryons rotating slower than the dark matter. At lower redshift, instead, the spin distributions of dark matter and gas track each other almost perfectly, as a consequence of a longer time interval available for momentum redistribution between the two components. The spin of both the gas and dark matter follows a lognormal distribution, with a mean value at z=16 of $=0.0184$, virtually independent of halo mass. This is in good agreement with previous studies. Using the results of two feedback models (MT1 and MT2) by McKee & Tan (2008) and mapping our halo spin distribution into a PopIII IMF, we find that at high-$z$ the IMF closely tracks the spin lognormal distribution. Depending on the feedback model, though, the distribution can be centered at $\approx 65 M_\odot$ (MT1) or $\approx 140 M_\odot$ (MT2). At later times, model MT1 evolves into a bimodal distribution with a second prominent peak located at $35-40 M_\odot$ as a result of the non-linear relation between rotation and halo mass. We conclude that the dark matter halo properties might be a key factor shaping the IMF of the first stars.Comment: 10 pages, 6 figures, accepted for publication in MNRA

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Chemistry of tropical eucheumatoids: Potential for food and feed applications

The use of seaweeds as additives in animal nutrition may be a valid option to traditional feed as they represent a rich source of minerals, carbohydrates and antioxidants. The aim of this study was to analyze the chemical composition and in vitro antioxidant capacity of two tropical eucheumatoids, Kappaphycus alvarezii and Kappaphycus striatus, in Malaysian wild offshore waters. The chemical analysis was performed via inductively coupled plasma–optical emission spectroscopy for evaluating the concentration of toxic (Cd, Pb, Hg, As) and essential elements (Mn, Fe, Cu, Ni, Zn, Se); NMR spectroscopy was used for carrageenans investigation. Furthermore, the soluble and fat-soluble antioxidant capacities were determined by FRAP, DPPH and ABTS assays. The chemical analysis revealed a higher content of trace elements in K. alvarezii as compared to K. striatus, and both exhibited a high mineral content. No significant differences in metal concentrations were found between the two species. Both samples showed a mixture of prevailing κ-and t-carrageenans. Finally, the levels of soluble and fat-soluble antioxidants in K. alvarezii were significantly higher than in K. striatus. Our findings suggest that K. alvarezii could be used as a potential feed additive because of its favorable chemical and nutritional features

Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients

Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication

Abnormal RasGRP1 Expression in the Post-Mortem Brain and Blood Serum of Schizophrenia Patients

Schizophrenia (SCZ) is a polygenic severe mental illness. Genome-wide association studies (GWAS) have detected genomic variants associated with this psychiatric disorder and pathway analyses have indicated immune system and dopamine signaling as core components of risk in dorsolateral-prefrontal cortex (DLPFC) and hippocampus, but the mechanistic links remain unknown. The RasGRP1 gene, encoding for a guanine nucleotide exchange factor, is implicated in dopamine signaling and immune response. RasGRP1 has been identified as a candidate risk gene for SCZ and autoimmune disease, therefore representing a possible point of convergence between mechanisms involving the nervous and the immune system. Here, we investigated RasGRP1 mRNA and protein expression in post-mortem DLPFC and hippocampus of SCZ patients and healthy controls, along with RasGRP1 protein content in the serum of an independent cohort of SCZ patients and control subjects. Differences in RasGRP1 expression between SCZ patients and controls were detected both in DLPFC and peripheral blood of samples analyzed. Our results indicate RasGRP1 may mediate risk for SCZ by involving DLPFC and peripheral blood, thus encouraging further studies to explore its possible role as a biomarker of the disease and/or a target for new medication

Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.

BACKGROUND: Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting. METHODS: Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data. RESULTS: Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia. CONCLUSION: EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors

A multidisciplinary study on the spatial variability of the local stratigraphic conditions in partially saturated slopes for flow-like landslide prediction

Flow-like landslides, which occur mainly in shallow granular deposits resting on steep bedrock, represent a major natural hazard worldwide. The pore water pressure distribution and the soil water content directly affect the soil shear strength, thus controlling the triggering of these landslides. Criticalgeomorphological and topographical settings, together with peculiar stratigraphic and hydrogeological features, are commonly recognized as predisposing factors for flow-like landslides occurrence. Hence, investigating the spatial and temporal variability of hydraulic slope conditions is a fundamental activity that consists of identifying local geological factors and seasonal monitoring of the subsurface water regime. The present work proposes an integrated geological, geophysical and geotechnical approach to identify the spatial variability of the local stratigraphic setting and hydrogeological conditions in a partially saturated slope, in order to set up a procedure able to provide a prediction of the flow-like landslides occurrence atslope scale. The multidisciplinary study has been applied to a test site on Mt. Faito, in the Lattari Mts. (Southern Italy), where extensive geophysical, geological and geotechnical soil characterization and in situmonitoring data collected over two years are available

A functional-cognitive framework for attitude research

In attitude research, behaviours are often used as proxies for attitudes and attitudinal processes. This practice is problematic because it conflates the behaviours that need to be explained (explanandum) with the mental constructs that are used to explain these behaviours (explanans). In the current chapter we propose a meta-theoretical framework that resolves this problem by distinguishing between two levels of analysis. According to the proposed framework, attitude research can be conceptualised as the scientific study of evaluation. Evaluation is defined not in terms of mental constructs but in terms of elements in the environment, more specifically, as the effect of stimuli on evaluative responses. From this perspective, attitude research provides answers to two questions: (1) Which elements in the environment moderate evaluation? (2) What mental processes and representations mediate evaluation? Research on the first question provides explanations of evaluative responses in terms of elements in the environment (functional level of analysis); research on the second question offers explanations of evaluation in terms of mental processes and representations (cognitive level of analysis). These two levels of analysis are mutually supportive, in that better explanations at one level lead to better explanations at the other level. However, their mutually supportive relation requires a clear distinction between the concepts of their explanans and explanandum, which are conflated if behaviours are treated as proxies for mental constructs. The value of this functional-cognitive framework is illustrated by applying it to four central questions of attitude research

Analysis of mRNA and Protein Levels of CAP2, DLG1 and ADAM10 Genes in Post‐Mortem Brain of Schizophrenia, Parkinson’s and Alzheimer’s Disease Patients

Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin‐binding protein cyclase‐associated protein 2 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post‐mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non‐psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. Interestingly, also in Parkinson’s disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies