University of Siena

About: University of Siena is a education organization based out in Siena, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 12179 authors who have published 33334 publications receiving 1008287 citations. The organization is also known as: Università degli studi di Siena & Universita degli studi di Siena.

ERS clinical practice guidelines on treatment of sarcoidosis

Abstract: Background The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin, or other manifestations. While glucocorticoids (GC) remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. GC-sparing alternatives are available. The presented treatment guideline aims to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations. Materials and Methods A European Respiratory Society Task Force (TF) committee composed of clinicians, methodologists, and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations. Results The TF committee delivered twelve recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac, and neurologic disease as well as fatigue. One PICO question regarding small fiber neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation. Conclusions There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment. Message An evidence based guideline for treatment of sarcoidosis is presented. The panel used the GRADE approach and specific recommendations are made. A major factor in treating patients is the risk of loss of organ function or impairment of quality of life.

Luminosity-independent measurements of total, elastic and inelastic cross-sections at \chem{\sqrt {s} = 7\,TeV}

Abstract: The TOTEM experiment at the LHC has performed the first luminosity-independent determination of the total proton-proton cross-section at . This technique is based on the optical theorem and requires simultaneous measurements of the inelastic rate – accomplished with the forward charged-particle telescopes T1 and T2 in the range 3.1 < |η| < 6.5 – and of the elastic rate by detecting the outcoming protons with Roman Pot detectors. The data presented here were collected in a dedicated run in 2011 with special beam optics (β* = 90 m) and Roman Pots approaching the beam close enough to register elastic events with squared four-momentum transfers |t| as low as 5·10−3 GeV2. The luminosity-independent results for the elastic, inelastic and total cross-sections are σel = (25.1 ± 1.1) mb, σinel = (72.9 ± 1.5) mb and σtot = (98.0 ± 2.5) mb, respectively. At the same time this method yields the integrated luminosity, in agreement with measurements by CMS. TOTEM has also determined the total cross-section in two complementary ways, both using the CMS luminosity measurement as an input. The first method sums the elastic and inelastic cross-sections and thus does not depend on the ρ parameter. The second applies the optical theorem to the elastic-scattering measurements only and therefore is free of the T1 and T2 measurement uncertainties. The methods, having very different systematic dependences, give results in excellent agreement. Moreover, the ρ-independent measurement makes a first estimate for the ρ parameter at possible: |ρ| = 0.145 ± 0.091.

Joint inversion of phase velocity dispersion and H/V ratio curves from seismic noise recordings using a genetic algorithm, considering higher modes

Abstract: [1] Seismic noise contains information on the local S-wave velocity structure, which can be obtained from the phase velocity dispersion curve by means of array measurements. The H/V ratio from single stations also contains information on the average S-wave velocity and the total thickness of the sedimentary cover. A joint inversion of the two data sets therefore might allow constraining the final model well. We propose a scheme that does not require a starting model because of usage of a genetic algorithm. Furthermore, we tested two suitable cost functions for our data set, using a-priori and data driven weighting. The latter one was more appropriate in our case. In addition, we consider the influence of higher modes on the data sets and use a suitable forward modeling procedure. Using real data we show that the joint inversion indeed allows for better fitting the observed data than using the dispersion curve only.

Germline CDH1 deletions in hereditary diffuse gastric cancer families

Abstract: Germline CDH1 point or small frameshift mutations can be identified in 30-50% of hereditary diffuse gastric cancer (HDGC) families. We hypothesized that CDH1 genomic rearrangements would be found in HDGC and identified 160 families with either two gastric cancers in first-degree relatives and with at least one diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in close relatives diagnosed at any age. Sixty-seven carried germline CDH1 point or small frameshift mutations. We screened germline DNA from the 93 mutation negative probands for large genomic rearrangements by Multiplex Ligation-Dependent Probe Amplification. Potential deletions were validated by RT-PCR and breakpoints cloned using a combination of oligo-CGH-arrays and long-range-PCR. In-silico analysis of the CDH1 locus was used to determine a potential mechanism for these rearrangements. Six of 93 (6.5%) previously described mutation negative HDGC probands, from low GC incidence populations (UK and North America), carried genomic deletions (UK and North America). Two families carried an identical deletion spanning 193 593 bp, encompassing the full CDH3 sequence and CDH1 exons 1 and 2. Other deletions affecting exons 1, 2, 15 and/or 16 were identified. The statistically significant over-representation of Alus around breakpoints indicates it as a likely mechanism for these deletions. When all mutations and deletions are considered, the overall frequency of CDH1 alterations in HDGC is approximately 46% (73/160). CDH1 large deletions occur in 4% of HDGC families by mechanisms involving mainly non-allelic homologous recombination in Alu repeat sequences. As the finding of pathogenic CDH1 mutations is useful for management of HDGC families, screening for deletions should be offered to at-risk families.

Theory and Simulation of the Ultrafast Double-Bond Isomerization of Biological Chromophores.

Abstract: Ultrafast processes in light-absorbing proteins have been implicated in the primary step in the light-to-energy conversion and the initialization of photoresponsive biological functions. Theory and computations have played an instrumental role in understanding the molecular mechanism of such processes, as they provide a molecular-level insight of structural and electronic changes at ultrafast time scales that often are very difficult or impossible to obtain from experiments alone. Among theoretical strategies, the application of hybrid quantum mechanics and molecular mechanics (QM/MM) models is an important approach that has reached an evident degree of maturity, resulting in several important contributions to the field. This review presents an overview of state-of-the-art computational studies on subnanosecond events in rhodopsins, photoactive yellow proteins, phytochromes, and some other photoresponsive proteins where photoinduced double-bond isomerization occurs. The review also discusses current limit...