Radiation-Related Dysphagia: From Pathophysiology to Clinical Aspects

In Western countries, head and neck cancers (HNCs) account for about 5% of all tumors. Due to tumor locations at the aero-digestive crossroad, patients frequently suffer from swallowing dysfunction caused both by primary cancer (baseline dysphagia) and cancer therapies (treatment-related dysphagia). In this regard, radiation-induced dysphagia represents a real “Achille’s heel” which historically occurs in more than 50% of patients and can lead to a malnutritional status and an increased risk of aspiration pneumonia. In fact radiotherapy, by restricting the driving pressure of the bolus through the pharynx and/or limiting the opening of the cricopharyngeal muscle, leads to a post-swallowing pharyngeal residue that may spill into the airway causing ab ingestis pneumonia. On the contrary, an organ preservation strategy should provide both the highest tumor control probability (TCP) and the minimum function impairment with the subsequent maximum therapeutic index gain. In this regard, intensity-modulated RT (IMRT) might reduce the probability of postradiation dysphagia by producing concave dose distributions with better avoidance of several critical structures, such as swallowing organs at risk (SWOARs), which might result in better functional outcomes. Similarly, a prompt swallowing rehabilitation provided before, during, and soon after radiotherapy plays an important role in improving oncologic swallowing outcomes

Loeys-Dietz syndrome type I and type II: clinical findings and novel mutations in two Italian patients

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disorder showing the involvement of cutaneous, cardiovascular, craniofacial, and skeletal systems. In particular, LDS patients show arterial tortuosity with widespread vascular aneurysm and dissection, and have a high risk of aortic dissection or rupture at an early age and at aortic diameters that ordinarily are not predictive of these events. Recently, LDS has been subdivided in LDS type I (LDSI) and type II (LDSII) on the basis of the presence or the absence of cranio-facial involvement, respectively. Furthermore, LDSII patients display at least two of the major signs of vascular Ehlers-Danlos syndrome. LDS is caused by mutations in the transforming growth factor (TGF) beta-receptor I (TGFBR1) and II (TGFBR2) genes. The aim of this study was the clinical and molecular characterization of two LDS patients

Dark Matter Results from 100 Live Days of XENON100 Data

We present results from the direct search for dark matter with the XENON100 detector, installed underground at the Laboratori Nazionali del Gran Sasso of INFN, Italy. XENON100 is a two-phase time projection chamber with a 62 kg liquid xenon target. Interaction vertex reconstruction in three dimensions with millimeter precision allows to select only the innermost 48 kg as ultra-low background fiducial target. In 100.9 live days of data, acquired between January and June 2010, no evidence for dark matter is found. Three candidate events were observed in a pre-defined signal region with an expected background of 1.8 +/- 0.6 events. This leads to the most stringent limit on dark matter interactions today, excluding spin-independent elastic WIMP-nucleon scattering cross-sections above 7.0x10^-45 cm^2 for a WIMP mass of 50 GeV/c^2 at 90% confidence level.Comment: 5 pages, 5 figures; matches accepted versio

Implications on Inelastic Dark Matter from 100 Live Days of XENON100 Data

The XENON100 experiment has recently completed a dark matter run with 100.9 live-days of data, taken from January to June 2010. Events in a 48kg fiducial volume in the energy range between 8.4 and 44.6 keVnr have been analyzed. A total of three events have been found in the predefined signal region, compatible with the background prediction of (1.8 \pm 0.6) events. Based on this analysis we present limits on the WIMP-nucleon cross section for inelastic dark matter. With the present data we are able to rule out the explanation for the observed DAMA/LIBRA modulation as being due to inelastic dark matter scattering off iodine at a 90% confidence level.Comment: 3 pages, 3 figure

Comment on "On the subtleties of searching for dark matter with liquid xenon detectors"

In a recent manuscript (arXiv:1208.5046) Peter Sorensen claims that XENON100's upper limits on spin-independent WIMP-nucleon cross sections for WIMP masses below 10 GeV "may be understated by one order of magnitude or more". Having performed a similar, though more detailed analysis prior to the submission of our new result (arXiv:1207.5988), we do not confirm these findings. We point out the rationale for not considering the described effect in our final analysis and list several potential problems with his study.Comment: 3 pages, no figure

Lowering the radioactivity of the photomultiplier tubes for the XENON1T dark matter experiment

The low-background, VUV-sensitive 3-inch diameter photomultiplier tube R11410 has been developed by Hamamatsu for dark matter direct detection experiments using liquid xenon as the target material. We present the results from the joint effort between the XENON collaboration and the Hamamatsu company to produce a highly radio-pure photosensor (version R11410-21) for the XENON1T dark matter experiment. After introducing the photosensor and its components, we show the methods and results of the radioactive contamination measurements of the individual materials employed in the photomultiplier production. We then discuss the adopted strategies to reduce the radioactivity of the various PMT versions. Finally, we detail the results from screening 216 tubes with ultra-low background germanium detectors, as well as their implications for the expected electronic and nuclear recoil background of the XENON1T experiment.Comment: 10 pages, 5 figure

Search for Event Rate Modulation in XENON100 Electronic Recoil Data

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an un-binned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1 sigma for all periods suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8 sigma, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of WIMPs to electrons is excluded at 4.8 sigma.Comment: 6 pages, 4 figure

Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis