Searching for Heavy Dark Matter near the Planck Mass with XENON1T.

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This Letter places strong constraints on spin-independent interactions of dark matter particles with a mass between 1×10^{12} and 2×10^{17} GeV/c^{2}. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross sections for dark matter particles with masses close to the Planck scale.

First Dark Matter Search with Nuclear Recoils from the XENONnT Experiment.

We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03) ton yr exposure used for this search, the intrinsic ^{85}Kr and ^{222}Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3) events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10^{-47} cm^{2} for a WIMP mass of 28 GeV/c^{2} at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure.

IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

BACKGROUND: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. METHODS: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. RESULTS: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. CONCLUSIONS: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

Needs of forensic psychiatric patients with schizophrenia in five European countries.

AIMS: The purpose was to compare the frequency of needs of patients with schizophrenia in forensic services across five European countries as assessed by both the patients and their care staff. METHODS: Patients with schizophrenia and a history of significant interpersonal violence were recruited from forensic psychiatric services in Austria, Germany, Italy, Poland and England. Participants' needs were assessed using the Camberwell Assessment of Needs-Forensic Version (CANFOR). Multiple linear regression analyses were used to identify predictors of numbers of needs. RESULTS: In this sample, (n = 221) the most commonly reported need according to patients (71.0%) and staff (82.8%) was the management of psychotic symptoms. A need for information was mentioned by about 45% of staff and patients. Staff members reported a significantly higher number of total needs than patients (mean 6.9 vs. 6.2). In contrast, staff members reported a significantly lower number of unmet needs than patients (mean 2.0 vs. 2.5). Numbers of total needs and met needs differed between countries. Unmet needs as reported by patients showed positive associations with the absence of comorbid personality disorder, with higher positive symptom scores and lifetime suicide or self-harm history. Significant predictors of unmet needs according to staff were absence of comorbid personality disorder and higher positive as well as negative symptom scores according to PANSS. CONCLUSIONS: Staff rated a significantly higher number of total needs than patients, while patients rated more unmet needs. This indicates that patients' self-assessments of needs yield important information for providing sufficient help and support.

Search for New Physics in Electronic Recoil Data from XENONnT.

We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.

New Horizons on Non-invasive Brain Stimulation of the Social and Affective Cerebellum.

The cerebellum is increasingly attracting scientists interested in basic and clinical research of neuromodulation. Here, we review available studies that used either transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) to examine the role of the posterior cerebellum in different aspects of social and affective cognition, from mood regulation to emotion discrimination, and from the ability to identify biological motion to higher-level social inferences (mentalizing). We discuss how at the functional level the role of the posterior cerebellum in these different processes may be explained by a generic prediction mechanism and how the posterior cerebellum may exert this function within different cortico-cerebellar and cerebellar limbic networks involved in social cognition. Furthermore, we suggest to deepen our understanding of the cerebro-cerebellar circuits involved in different aspects of social cognition by employing promising stimulation approaches that have so far been primarily used to study cortical functions and networks, such as paired-pulse TMS, frequency-tuned stimulation, state-dependent protocols, and chronometric TMS. The ability to modulate cerebro-cerebellar connectivity opens up possible clinical applications for improving impairments in social and affective skills associated with cerebellar abnormalities.

Long-term use of pharmacological treatment in Alzheimer's disease: a retrospective cohort study in real-world clinical practice.

PURPOSE: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression. METHODS: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10. RESULTS: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression. CONCLUSION: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.

A large light-mass component of cosmic rays at 10(17)-10(17.5) electronvolts from radio observations.

Cosmic rays are the highest-energy particles found in nature. Measurements of the mass composition of cosmic rays with energies of 10(17)-10(18) electronvolts are essential to understanding whether they have galactic or extragalactic sources. It has also been proposed that the astrophysical neutrino signal comes from accelerators capable of producing cosmic rays of these energies. Cosmic rays initiate air showers--cascades of secondary particles in the atmosphere-and their masses can be inferred from measurements of the atmospheric depth of the shower maximum (Xmax; the depth of the air shower when it contains the most particles) or of the composition of shower particles reaching the ground. Current measurements have either high uncertainty, or a low duty cycle and a high energy threshold. Radio detection of cosmic rays is a rapidly developing technique for determining Xmax (refs 10, 11) with a duty cycle of, in principle, nearly 100 per cent. The radiation is generated by the separation of relativistic electrons and positrons in the geomagnetic field and a negative charge excess in the shower front. Here we report radio measurements of Xmax with a mean uncertainty of 16 grams per square centimetre for air showers initiated by cosmic rays with energies of 10(17)-10(17.5) electronvolts. This high resolution in Xmax enables us to determine the mass spectrum of the cosmic rays: we find a mixed composition, with a light-mass fraction (protons and helium nuclei) of about 80 per cent. Unless, contrary to current expectations, the extragalactic component of cosmic rays contributes substantially to the total flux below 10(17.5) electronvolts, our measurements indicate the existence of an additional galactic component, to account for the light composition that we measured in the 10(17)-10(17.5) electronvolt range.

Incomplete penetrance in familial Alzheimer's disease with PSEN1 Ala260Gly mutation.

Presenilin1 (PSEN1) gene is the most common known genetic cause of early-onset familial Alzheimer's disease. We describe an Italian family with the known p.Ala260Gly mutation in PSEN1 gene. The presence of an asymptomatic 64-year-old male carrying the mutation provides evidence of a possible incomplete penetrance leading to a wider range of age at onset. In order to evaluate whether or not epigenetic modifications could contribute to the phenotypic heterogeneity, we assessed global DNA methylation levels which resulted significantly higher in the three females than in their presymptomatic brother. The study suggests that DNA methylation can contribute to slowing down or possibly protecting from the manifestation of symptoms even in monogenic diseases, emphasizing the great complexity of familial Alzheimer's disease.

Extra-long and taper-free germanium nanowires: use of an alternative Ge precursor for longer nanostructures.

One of the challenges in the development of germanium nanowires (Ge NWs) is to increase their length beyond the 10 µm limit without enlarging the NW diameter, i.e. minimizing the tapering. Here we report how it is possible to overcome this hurdle by using isobutyl germane (iBuGe) as a metal organic precursor during MOCVD growth, instead of the commonly used germane. We have grown and characterized by transmission electron microscopy, scanning electron microscopy and Raman various samples and we have analyzed the effect of growth time, precursor flux and growth temperature on the NW length. The use of iBuGe coupled to optimized growth conditions permitted to obtain Ge NWs with lengths up to 30 µm with minimal tapering. To explain why a new precursor has this impact on the morphology of the NWs we consider two possible causes: (i) the role of carbon radicals produced by isobutyl decomposition and (ii) the reduced growth rate of Ge on the sidewalls. On the basis of Raman characterization and temperature-dependence of tapering, we conclude that the reduced tapering is probably due to lower growth rates on the sidewalls.

Use of amyloid PET/CT with 18F-Florbetaben in the management of patients with Alzheimer's disease.

INTRODUCTION AND AIM: Amyloid PET/CT is an "in vivo" imaging that may radically change management of Alzheimer's disease (AD) thanks to its ability to identify AD at the earliest stage. A diagnosis of dementia is currently made in terms of probability and is based on clinical evaluation (neuropsycological tests) as well as on the results of morphological imaging investigations (MRI) that can be supported by biohumoral (CSF analysis), and functional imaging only in the case of uncertain diagnosis of disease. The present study aimed to evaluate the role of amyloid PET/CT in the management of patients with suspicion of AD, through comparison with instrumental and clinical evaluation. METHODS: 38 consecutive patients with suspicion of AD (23 female, 15 male; median age 63 years old, range 46-72), who performed 18F-florbetaben PET/CT, were retrospectively reviewed. All of them performed a previous instrumental evaluation. A subgroup of patients (24/38) were evaluated with Mini Mental State Examination (MMSE). Cohen's K test was used as a measure of agreement between previous instrumental examinations/clinical evaluation and beta-amyloid PET results. RESULTS: Twenty-five/38 (65.8%) amyloid PET/CT scans resulted positive for amyloid deposition. Among the four target regions, precuneus was the most frequently involved. Previous instrumental evaluation was: MRI in 26/38 patients (24/26 positive for atrophy), CT in 9/38 (8/9 positive for atrophy), perfusion SPECT in 12/38 (8/12 areas of hypo-perfusion), 18F-FDG PET/CT in 2/38 (1/2 hypometabolism in frontal cortex). The agreement between previous instrumental examinations and beta-amyloid PET results was low (K= 0.084). In the subgroup of 24/38 patients, MMSE was scored positive (MMSE<24) in 14/24 (58.4%) and negative (MMSE>24) in 10/24 (41.6%). The agreement between clinical evaluation (MMSE) and beta-amyloid PET results was fair (K= 0.217). CONCLUSION: The low agreement between amyloid PET/CT and previous clinical and instrumental assessments that we found in our study suggests that the amyloid PET/CT provides additional and early information. To perform an early and differential diagnosis of AD could have a great impact on the patient's management and cost of care in order to perform the correct therapeutic interventions and to allow family members to manage adequately the patient's demanding care.

Impact of pre-treatment variables on the completion of 223radium-dichloride therapy in mCRPC patients with bone metastases.

INTRODUCTION: Radium-223 dichloride (223Ra) is an alpha-particle-emitter radiopharmaceutical, approved for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral involvement. Its administration is based on a schedule of intravenous injection (55kBq/kg) every four weeks for up to six cycles. Because the biological effectiveness of 223Ra-therapy is dose-dependent, the main goal is to complete the entire treatment to achieve a better patient outcome. This study aims to identify potential pre-treatment variables that could impact on 223Ra-treatment completion and then be used to improve the clinical and supportive management of mCRPC patients. MATERIALS AND METHODS: 30 consecutive mCRPC patients (mean age 77 years old), who were admitted for Ra223-therapy at our Department from February 2016 to October 2018, were enrolled for the analysis. The population was grouped as patients who completed 223Ra-therapy (group Ra223-C) and patients who do not (group 223Ra-U). For each group, we analyzed the effects of potential pre-treatment variables (age, Gleason Score, tumor burden, "Time From Diagnosis To 223Ra therapy", type and number of previous treatments, hemoglobin level, Alkaline Phosphatase, Prostate Specific Antigen and pain) on the Ra223-therapy completion. Statistical analysis was performed to evaluate the association between the completion of 223Ra therapy and the variables examined. RESULTS: 16/30 (53%) patients were 223Ra-C, conversely 14/30 (47%) patients were 223Ra-U because of an early interrupted treatment. A statistically significant association was found only with tumor burden: 68.7% of patients who completed 223-therapy had less than 20 bone metastases (χ2=4.821, p=0.028). CONCLUSION: Our preliminary analysis demonstrates that the high tumor burden represents the most important pre-treatment factor that could affect treatment completion and that needs to be considered before starting 223Ra-therapy to achieve a better outcome in mCRPC patients.

The paleoradiology importance in the study of relics: the unique densitometric analysis of a bone relic of Saint Nicholas.

INTRODUCTION: DXA have greatly contributed to the development of paleoradiology, a branch of diagnostic imaging that allows to obtain information about human remains in contexts of archaeological and/or forensic interest. In this manuscript we report the unique experience of DXA performed on the relic of a Saint; in particular we analyzed a skeletal fragment of St. Nicholas, kept in the Basilica of Bari (Italy) since 1087. MATERIALS AND METHODS: The bone to be examined consisted of the posterior arch of the ninth left rib that was 12cm long, 1.2cm maximum width and 1.7cm thick at the body. The data acquired from the densitometric study were performed using the anthropometric measures reported in historical records of St. Nicholas' life: sex (male), age (75 years), weight (70kg), height (167cm), and ethnicity (Caucasian). In addition to the examination of the relic, a comparison assessment was made with the rib of a healthy 60 years old man (height of 170cm, without known skeletal pathologies). This sample had a length of 19cm, maximum width at the head 1cm, and 0.7cm thick at the body. The analysis of bone fragments is different from the analysis of bones in the context of the human body (where soft tissues are placed around the skeleton); for this reason, one of the most critical issues was to create a support that would allow the analysis of bone fragments. We simulated conditions similar to those occurring in patients: a density scale was established, using a specific plexiglass phantom on which the bone fragments to be examined were placed. From the analysis it was calculated the parameter bone mineral density (BMD), express in g/cm2, that indicates the relation between mass of bone mineral content and area of examined bone segment. BMD data was compared to a range normalized by age, sex and ethnicity (BMD-N). RESULTS: The results of the scannnig of St. Nicholas' rib showed a BMD of 0.97g/cm2 with a BMD-N between 0.77 and 1.08g/cm2. Simultaneous measurements of the relic compared with a reference rib showed highlighted BMD of 0.84g/cm2 for the relic and 0.50g/cm2 for the reference rib. The St. Nicholas data are 168% higher than reference bone. All our measurements of the relic indicated a high bone mineral density, most likely due to the presence of a high concentration of calcium salts. A relatively higher mineral density of the relic was seen compared to the healthy subject's rib. From the history of St Nicholas' life, we know of the long imprisonment at the age of 51 in damp and unhealthy environment. The results of this study suggest that a good bone mineral density was maintained by the Saint even in old age. An additional element that can influence bone mineral density is diet, certainly different during the time of St. Nicholas. The good bone densitometry indicates that the Saint maintained a proper diet, with a generally fair state of health. CONCLUSION: For this first DXA analysis of the rib relic of Saint Nicholas was necessary a long and complex experimental work to modify standard technique procedure to particular and unusual sample and Create specific supports and complementary instruments. Perform DXA analysis on relics permit to obtain additional information to living conditions, economical situation, behaviours, diet, diseaes, conservations conditions of remains, change of life style in different age. Our experimental work, the first of its kind, creates the way to analyze precious relics that often include only few bone fragments and data obtained by our work can be useful for a better management and movement of fragile relics. We ourselves are working on a new challenge for the analysis of bone finds from shipwrecks found at the bottom of the sea.

Ultrasound-assessed visceral fat and associations with glucose homeostasis and cardiovascular risk in clinical practice.

BACKGROUND AND AIMS: Despite the lack of evidence that assessing the global cardiovascular risk leads to a decreased incidence of cardiovascular events, accurate patient profiling is paramount in preventive medicine. An excess of visceral fat (VF) is associated with an enhanced cardiovascular risk; importantly, VF is quantifiable rapidly, cheaply and safely by ultrasound, which makes it suitable for use in clinical practice. In the present study, we aimed to evaluate if US-measured VF (USVF) could be a better predictor of glucose homeostasis and cardiovascular risk than simple anthropometric measures. METHODS AND RESULTS: One-hundred sixty-two patients attending a Metabolic Disorders Clinic underwent a cross-sectional study for which USVF, anthropometric measures, a standard oral glucose tolerance test (OGTT), and calculation of cardiovascular Framingham score and vascular age were obtained. USVF was directly correlated with fasting and 2-h plasma glucose (respectively: r = 0.26, p < 0.001; r = 0.28, p < 0.0001), fasting and 2-h plasma insulin (for both: r = 0.41, p < 0.0001), homeostatic model assessment of insulin resistance (HOMA-IR; r = 0.42, p < 0.0001), cardiovascular Framingham score (r = 0.44 p < 0.0001) and vascular age (r = 0.30 p < 0.001). In receiver operator characteristic curves USVF had good diagnostic abilities for type 2 diabetes mellitus, fatty liver and metabolic syndrome, in both genders. At multivariate analysis, body mass index (BMI) outperformed USVF in the prediction of HOMA-IR; neverthless, USVF, not BMI, was an independent predictor of cardiovascular risk. Finally, models including USVF were the most parssimonious to predict Framingham score, vascular age and HOMA-IR. CONCLUSION: In overweight and obese subjects, USVF could usefully complement other parameters for cardiovascular risk stratification.

Blindness and social trust: The effect of early visual deprivation on judgments of trustworthiness.

Investigating the impact of early visual deprivation on evaluations related to social trust has received little attention to date. This is despite consistent evidence suggesting that early onset blindness may interfere with the normal development of social skills. In this study, we investigated whether early blindness affects judgments of trustworthiness regarding the actions of an agent, with trustworthiness representing the fundamental dimension in the social evaluation. Specifically, we compared performance between a group of early blind individuals with that of sighted controls in their evaluation of trustworthiness of an agent after hearing a pair of two positive or two negative social behaviors (impression formation). Participants then repeated the same evaluation following the presentation of a third (consistent or inconsistent) behavior regarding the same agent (impression updating). Overall, blind individuals tended to give similar evaluations compared to their sighted counterparts. However, they also valued positive behaviors significantly more than sighted controls when forming their impression of an agent's trustworthiness. Moreover, when inconsistent information was provided, blind individuals were more prone to revise their initial evaluation compared to controls. These results suggest that early visual deprivation may have a dramatic effect on the evaluation of social factors such as trustworthiness.

Composite infrared spectrometer (CIRS) on Cassini.

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

Composite infrared spectrometer (CIRS) on Cassini: publisher's note.

This publisher's note renumbers the reference list in Appl. Opt.56, 5274 (2017)APOPAI0003-693510.1364/AO.56.005274.

Interleukin 28B polymorphisms as predictors of sustained virological response in chronic hepatitis C: systematic review and meta-analysis.

Polymorphism of interleukin 28B gene represents a powerful outcome predictor for interferon-based regimens in hepatitis C virus infection. However, some studies report conflicting results. The predictive value of interleukin 28B genotype over the outcome interferon-α/ribavirin treatment was thoroughly evaluated and compared with virological predictors of response. Literature revision was performed on PubMed. Pooled odds ratios (ORs) were calculated by fixed- or random-effects models. Heterogeneity and publication bias were also assessed. Sixty-two eligible papers including 20 290 patients were retrieved. Both polymorphisms (rs12979860 and rs8099917) were strongly associated with response (OR=4.09 and 4.00, respectively), however, the association was weaker for subjects infected with viral genotypes 2 and 3 (OR=1.52 and 1.49, respectively). Compared with interleukin 28B genotype, the association with response was lower for baseline viremia (OR=2.15) and higher for rapid virological response (OR=13.86). These results provide a critical evaluation of interleukin 28B genotype as a pharmacogenetic predictor in hepatitis C patients.