Playing with fermion couplings in Higgsless models

We discuss the fermion couplings in a four dimensional SU(2) linear moose model by allowing for direct couplings between the left-handed fermions on the boundary and the gauge fields in the internal sites. This is realized by means of a product of non linear $\sigma$-model scalar fields which, in the continuum limit, is equivalent to a Wilson line. The effect of these new non local couplings is a contribution to the $\epsilon_3$ parameter which can be of opposite sign with respect to the one coming from the gauge fields along the string. Therefore, with some fine tuning, it is possible to satisfy the constraints from the electroweak data.Comment: Latex file, 20 pages, 4 eps figure

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

Chromatin Protamination and Catsper Expression in Spermatozoa Predict Clinical Outcomes after Assisted Reproduction Programs

Abstract Identification of parameters predicting assisted reproductive technologies (ARTs) success is a major goal of research in reproduction. Quality of gametes is essential to achieve good quality embryos and increase the success of ARTs. We evaluated two sperm parameters, chromatin maturity and expression of the sperm specific calcium channel CATSPER, in relation to ART outcomes in 206 couples undergoing ARTs. Chromatin maturity was evaluated by Chromomycin A3 (CMA3) for protamination and Aniline Blue (AB) for histone persistence and CATSPER expression by a flow cytometric method. CMA3 positivity and CATSPER expression significantly predicted the attainment of good quality embryos with an OR of 6.6 and 14.3 respectively, whereas AB staining was correlated with fertilization rate. In the subgroup of couples with women ≤35 years, CATSPER also predicted achievement of clinical pregnancy (OR = 4.4). Including CMA3, CATSPER and other parameters affecting ART outcomes (female age, female factor and number of MII oocytes), a model that resulted able to predict good embryo quality with high accuracy was developed. CMA3 staining and CATSPER expression may be considered two applicable tools to predict ART success and useful for couple counseling. This is the first study demonstrating a role of CATSPER expression in embryo development after ARTs programs

Optical coherence tomography angiography findings in Huntington’s disease

Objectives: To evaluate the retinal and choriocapillaris vascular networks in macular region and the central choroidal thickness (CCT) in patients affected by Huntington disease (HD), using optical coherence tomography angiography (OCTA) and enhanced depth imaging spectral-domain OCT (EDI SD-OCT). Methods: We assessed the vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using OCTA, while CCT was measured by EDI SD-OCT. Results: Sixteen HD patients (32 eyes) and thirteen healthy controls (26 eyes) were enrolled in this prospective study. No significant difference in retinal and choriocapillaris VD was found between HD patients and controls while CCT turned to be thinner in patients respect to controls. There were no significant relationships between OCTA findings and neurological parameters. Conclusion: The changes in choroidal structure provide useful information regarding the possible neurovascular involvement in the physiopathology of HD. Choroidal vascular network could be a useful parameter to evaluate the vascular impairment that occurs in this neurodegenerative disease

Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives

Aspartate has a central role in cancer cell metabolism. Aspartate cytosolic availability is crucial for protein and nucleotide biosynthesis as well as for redox homeostasis. Since tumor cells display poor aspartate uptake from the external environment, most of the cellular pool of aspar-tate derives from mitochondrial catabolism of glutamine. At least four transporters are involved in this metabolic pathway: the glutamine (SLC1A5_var), the aspartate/glutamate (AGC), the as-partate/phosphate (uncoupling protein 2, UCP2), and the glutamate (GC) carriers, the last three belonging to the mitochondrial carrier family (MCF). The loss of one of these transporters causes a paucity of cytosolic aspartate and an arrest of cell proliferation in many different cancer types. The aim of this review is to clarify why different cancers have varying dependencies on metabolite transporters to support cytosolic glutamine-derived aspartate availability. Dissecting the precise metabolic routes that glutamine undergoes in specific tumor types is of upmost importance as it promises to unveil the best metabolic target for therapeutic intervention

Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study

Background: Celiac disease (CD) is an autoimmune enteropathy in which HLA-DQ haplotypes define susceptibility. Our aim was to evaluate if belonging to a certain HLA-DQ class risk could be associated to the clinical, serological and histological presentation of CD. Methods: We performed a retrospective observational monocentric study including all 300 patients diagnosed with CD, who underwent HLA typing. Clinical, serological and histological data was collected from clinical records and their association with HLA-DQ class risk was verified through statistical tests. Results: In our sample mean age at onset was 6.7 ± 4.2 years, with a prevalence of females (n = 183; 61%), typical symptoms (n = 242; 80.6%) and anti-tTG IgA ≥ 100 U/mL (n = 194; 64.7%). Family history was present only in 19% (n = 57) of patients, and it was not significantly associated with any of the clinical and demographical data analyzed or the belonging to a certain HLA-DQ class risk. We found in the male population more frequently a coexistence of CD and atopic syndrome (males: n = 47; 40.2%; females: n = 50; 27.3%; p = 0.020). Early age of onset, instead, was associated with typical symptoms (m = 6.4 ± 4; p = 0.045) and elevated liver enzymes (m = 5 ± 3.8; p < 0.001), while later age of onset was associated with presence of other autoimmune diseases (m = 8.2 ± 4; p = 0.01). We observed statistically significant influences of HLA class risk on antibodies and liver enzymes levels: G1, G4 and G2 classes showed more frequently anti-tTG IgA ≥ 100 U/mL (n = 44; 80%, n = 16; 69.6%, n = 48; 67.6% respectively; p-value = 0.037), and in patients from G2 class we found enhanced liver enzymes (n = 28; 39.4%; p-value = 0.005). HLA class risk was still significantly associated with anti-tTG ≥ 100 (p = 0.044) and with hypertransaminasemia (p = 0.010) after a multiple logistic regression adjusted for the effect of gender, age at onset and family history. Conclusions: We failed to prove an association between HLA-DQ genotypes and the clinical features in our CD pediatric patients. Although, our results suggest an effect of the DQB1–02 allele not only on the level of antibodies to tTG, but possibly also on liver involvement

High Grade Glioma Treatment in Elderly People: Is It Different Than in Younger Patients? Analysis of Surgical Management Guided by an Intraoperative Multimodal Approach and Its Impact on Clinical Outcome

Objective: Age is considered a negative prognostic factor for High Grade Gliomas (HGGs) and many neurosurgeons remain skeptical about the benefits of aggressive treatment. New surgical and technological improvements may allow extended safe resection, with lower level of post-operative complications. This opportunity opens the unsolved question about the most appropriate HGG treatment in elderly patients. The aim of this study is to analyze if HGG maximal safe resection guided by an intraoperative multimodal imaging protocol coupled with neuromonitoring is associated with differences in outcome in elderly patients versus younger ones. Methods: We reviewed 100 patients, 53 (53%) males and 47 (47%) females, with median (IQR) age of 64 (57; 72) years. Eight patients were diagnosed with Anaplastic Astrocytoma (AA), 92 with Glioblastoma (GBM). Surgery was aimed to achieve safe maximal resection. An intraoperative multimodal imaging protocol, including neuronavigation, neurophysiological monitoring, 5-ALA fluorescence, 11C MET-PET, navigated i-US system and i-CT, was used, and its impact on EOTR and clinical outcome in elderly patients was analyzed. We divided patients in two groups according to their age: 65 years, and surgical and clinical results (EOTR, post-operative KPS, OS and PFS) were compared. Yet, to better understand age-related differences, the same patient cohort was also divided into 70 years and all the above data reanalyzed. Results: In the first cohort division, we did not found KPS difference over time and survival analysis did not show significant difference between the two groups (p = 0.36 for OS and p = 0.49 for PFS). Same results were obtained increasing the age cut-off for age up to 70 years (p = 0.52 for OS and p = 0.92 for PFS). Conclusions: Our data demonstrate that there is not statistically significant difference in post-operative EOTR, KPS, OS, and PFS between younger and elderly patients treated with extensive tumor resection aided by a intraoperative multimodal protocol

Overview of the Italian strong Motion database ITACA 1.0

The Italian Strong Motion Database, ITACA, was developed within projects 2 S6 and S4, funded in the framework of the agreements between the Italian Department of 3 Civil Protection (Dipartimento della Protezione Civile, DPC) and the Istituto Nazionale di 4 Geofisica e Vulcanologia (INGV), starting from 2005. The alpha version of the database 5 was released in 2007 and subsequently upgraded to version 1.0 after: (i) including the most 6 recent strongmotion data (from2005 to 2007) recorded in Italy, in addition to the 2008 Parma 7 earthquake, M 5.4, and the M 4.0, 2009 Abruzzo seismic events; (ii) processing the raw 8 strong motion data using an updated procedure; (iii) increasing the number of stations with a 9 measured shear wave velocity profile; (iv) improving the utilities to retrieve time series and 10 ground motion parameters; (v) implementing a tool for selecting time series in agreement 11 with design-response spectra; (vi) compiling detailed station reports containing miscella12 neous information such as photo, maps and site parameters; (vii) developing procedures for 13 the automatic generation of station reports and for the updating of the header files. After such 14 improvements, ITACA 1.0 was published at the web site http://itaca.mi.ingv.it, in 2010. It 15 presently contains 3,955 three-component waveforms, comprising the most complete cata16 logue of the Italian accelerometric records in the period 1972–2007 (3,562 records) and the 17 strongest events in the period 2008–2009. Records were mainly acquired by DPC through its 18 Accelerometric National Network (RAN) and, in few cases, by local networks and temporary 19 stations or networks. This paper introduces the published version of the Italian StrongMotion 20 database (ITACA version 1.0) together with main improvements and new functionalities

Seismic Damage Accumulation of Highway Bridges in Earthquake Prone Regions

Civil infrastructures, such as highway bridges, located in seismically active regions are often subjected to multiple earthquakes, such as multiple main shocks along their service life or main shock-aftershock sequences. Repeated seismic events result in reduced structural capacity and may lead to bridge collapse causing disruption in normal functioning of transportation networks. This study proposes a framework to predict damage accumulation in structures under multiple shock scenarios after developing damage index prediction models and accounting for the probabilistic nature of the hazard. The versatility of the proposed framework is demonstrated on a case study highway bridge located in California for two distinct hazard scenarios: a) multiple main shocks along the service life, and b) multiple aftershock earthquake occurrences following a single main shock. Results reveal that in both cases there is a significant increase in damage index exceedance probabilities due to repeated shocks within the time window of interest

Comparative analysis of density histograms and visual scores in incremental and volumetric high-resolution computed tomography of the chest in idiopathic pulmonary fibrosis patients

Background: Volumetric high-resolution computed tomography (HRCT) of the chest has recently replaced incremental CT in the diagnostic workup of idiopathic pulmonary fibrosis (IPF). Concomitantly, visual and quantitative scores have been proposed for disease extent assessment to ameliorate disease management. Purpose: To compare the performance of density histograms (mean lung attenuation, skewness, and kurtosis) and visual scores, along with lung function correlations, in IPF patients submitted to incremental or volumetric thorax HRCT. Material and methods: Clinical data and CT scans of 89 newly diagnosed and therapy-naive IPF patients were retrospectively evaluated. Results: Forty-six incremental and 43 volumetric CT scans were reviewed. No differences of density histograms and visual scores estimates were found by comparing two HRCT techniques, with an optimal inter-operator agreement (concordance correlation coefficient >0.90 in all instances). Single-breath diffusing lung capacity for carbon monoxide (DLCOsb) was inversely related with the Best score (r = −00.416; p = 0.014), the Kazerooni fibrosis extent (r = −0.481; p = 0.004) and the mean lung attenuation (r = −0.382; p = 0.026), while a positive correlation was observed with skewness (r = 0.583; p = 0.001) and kurtosis (r = 0.543; p = 0.001) in the incremental HRCT sub-group. Similarly, in the volumetric CT sub-cohort, DLCOsb was significantly associated with skewness (r = 0.581; p = 0.007) and kurtosis (r = 0.549; p = 0.018). Correlations with visual scores were not confirmed. Forced vital capacity significantly related to all density indices independently on HRCT technique. Conclusions: Density histograms and visual scores similarly perform in incremental and volumetric HRCT. Density quantification displays an optimal reproducibility and proves to be superior to visual scoring as more strongly correlated with lung function