An estimate of theta_14 independent of the reactor antineutrino flux determinations

In a previous paper [Phys. Rev. D 83, 113013 (2011)] we have shown that the solar sector data (solar and KamLAND) are sensitive to the parameter theta_14, encoding the admixture of the electron neutrino with a fourth (essentially) sterile mass eigenstate. In that work we evidenced that such data prefer a non-zero value of theta_14 and that such a preference is completely degenerate with that of non-zero theta_13. In this report we show how the evidence of theta_13 > 0, recently emerged from global neutrino data analyses, lifts such a degeneracy and disfavors the case of sterile neutrino mixing. By excluding from our analysis the total rate information coming from the reactor experiments we untie our results from any assumption on their flux normalization. In this way, we establish the robust upper bound sin^2 (theta_14) < 0.04 at the 90% C.L.Comment: 4 pages, 1 figure, minor changes, matches version accepted by PR

Observables sensitive to absolute neutrino masses: A reappraisal after WMAP-3y and first MINOS results

In the light of recent neutrino oscillation and non-oscillation data, we revisit the phenomenological constraints applicable to three observables sensitive to absolute neutrino masses: The effective neutrino mass in single beta decay (m_beta); the effective Majorana neutrino mass in neutrinoless double beta decay (m_2beta); and the sum of neutrino masses in cosmology (Sigma). In particular, we include the constraints coming from the first Main Injector Neutrino Oscillation Search (MINOS) data and from the Wilkinson Microwave Anisotropy Probe (WMAP) three-year (3y) data, as well as other relevant cosmological data and priors. We find that the largest neutrino squared mass difference is determined with a 15% accuracy (at 2-sigma) after adding MINOS to world data. We also find upper bounds on the sum of neutrino masses Sigma ranging from ~2 eV (WMAP-3y data only) to ~0.2 eV (all cosmological data) at 2-sigma, in agreement with previous studies. In addition, we discuss the connection of such bounds with those placed on the matter power spectrum normalization parameter sigma_8. We show how the partial degeneracy between Sigma and sigma_8 in WMAP-3y data is broken by adding further cosmological data, and how the overall preference of such data for relatively high values of sigma_8 pushes the upper bound of Sigma in the sub-eV range. Finally, for various combination of data sets, we revisit the (in)compatibility between current Sigma and m_2beta constraints (and claims), and derive quantitative predictions for future single and double beta decay experiments.Comment: 18 pages, including 7 figure

Undiagnosed Primary Hyperparathyroidism and Recurrent Miscarriage: The First Prospective Pilot Study.

BACKGROUND: Primary hyperparathyroidism (pHPT) in pregnancy is reported to be associated with significant maternal and foetal complications and an up to threefold increase in the risk of miscarriage. However, the true incidence of pHPT in pregnancy, complete and miscarried, is unknown and there are no data on the prevalence of undiagnosed pHPT in recurrent miscarriage (RM) (≥3 consecutive miscarriages under 24-week gestation). This is the first prospective study aiming to establish the prevalence of undiagnosed pHPT in RM. METHODS: Following UK National ethics committee approval, women who had experienced 3 or more consecutive miscarriages were recruited from a nationwide RM clinic. Serum corrected calcium, phosphate, PTH and vitamin D were evaluated. Patients with raised serum calcium and/or PTH were recalled for confirmatory tests. Power calculations suggested that a minimum of 272 patients were required to demonstrate a clinically significant incidence of pHPT. RESULTS: Three hundred women were recruited, median age 35 years (range 19-42). Eleven patients had incomplete data, leaving 289 patients suitable for analysis; 50/289 patients (17%) with abnormal tests were recalled. The prevalence of vitamin D deficiency (<25 nmol/l) and insufficiency (25-75 nmol/l) was 8.7 and 67.8%, respectively. One patient was diagnosed with pHPT (0.34%) and underwent successful parathyroidectomy. CONCLUSIONS: The prevalence of undiagnosed pHPT (0.34%) in RM in this study appears to be many times greater than the 0.05% expected in this age group. The findings of this pilot study merit follow-up with a larger-scale study. Routine serum calcium estimation is not currently undertaken in RM and should be considered

Geo-neutrinos: A systematic approach to uncertainties and correlations

Geo-neutrinos emitted by heat-producing elements (U, Th and K) represent a unique probe of the Earth interior. The characterization of their fluxes is subject, however, to rather large and highly correlated uncertainties. The geochemical covariance of the U, Th and K abundances in various Earth reservoirs induces positive correlations among the associated geo-neutrino fluxes, and between these and the radiogenic heat. Mass-balance constraints in the Bulk Silicate Earth (BSE) tend instead to anti-correlate the radiogenic element abundances in complementary reservoirs. Experimental geo-neutrino observables may be further (anti)correlated by instrumental effects. In this context, we propose a systematic approach to covariance matrices, based on the fact that all the relevant geo-neutrino observables and constraints can be expressed as linear functions of the U, Th and K abundances in the Earth's reservoirs (with relatively well-known coefficients). We briefly discuss here the construction of a tentative "geo-neutrino source model" (GNSM) for the U, Th, and K abundances in the main Earth reservoirs, based on selected geophysical and geochemical data and models (when available), on plausible hypotheses (when possible), and admittedly on arbitrary assumptions (when unavoidable). We use then the GNSM to make predictions about several experiments ("forward approach"), and to show how future data can constrain - a posteriori - the error matrix of the model itself ("backward approach"). The method may provide a useful statistical framework for evaluating the impact and the global consistency of prospective geo-neutrino measurements and Earth models.Comment: 17 pages, including 4 figures. To appear on "Earth, Moon, and Planets," Special Issue on "Neutrino Geophysics," Proceedings of Neutrino Science 2005 (Honolulu, Hawaii, Dec. 2005

MIDGARD: A Simulation Platform for Autonomous Navigation in Unstructured Environments

We present MIDGARD, an open-source simulation platform for autonomous robot navigation in outdoor unstructured environments. MIDGARD is designed to enable the training of autonomous agents (e.g., unmanned ground vehicles) in photorealistic 3D environments, and to support the generalization skills of learning-based agents through the variability in training scenarios. MIDGARD's main features include a configurable, extensible, and difficulty-driven procedural landscape generation pipeline, with fast and photorealistic scene rendering based on Unreal Engine. Additionally, MIDGARD has built-in support for OpenAI Gym, a programming interface for feature extension (e.g., integrating new types of sensors, customizing exposing internal simulation variables), and a variety of simulated agent sensors (e.g., RGB, depth and instance/semantic segmentation). We evaluate MIDGARD's capabilities as a benchmarking tool for robot navigation utilizing a set of state-of-the-art reinforcement learning algorithms. The results demonstrate MIDGARD's suitability as a simulation and training environment, as well as the effectiveness of our procedural generation approach in controlling scene difficulty, which directly reflects on accuracy metrics. MIDGARD build, source code and documentation are available at https://midgardsim.org/

TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients.

INTRODUCTION: Circulating tumor cells (CTCs) are tumor cells shed from either primary tumors or its metastases that circulate in the peripheral blood of patients with metastatic cancers. The molecular characterization of the CTCs is critical to identifying the key drivers of cancer metastasis and devising therapeutic approaches. However, the molecular characterization of CTCs is difficult to achieve because their isolation is a major technological challenge. METHODS: CTCs from two triple negative breast cancer patients were enriched using CellSearch and single cells selected by DEPArray™. A TP53 R110 fs*13 mutation identified by next generation sequencing in the breast and chest skin biopsies of both patients was studied in single CTCs. RESULTS: From 6 single CTC isolated from one patient, 1 CTC had TP53 R110 delC, 1 CTC showed the TP53 R110 delG mutation, and the remaining 4 single CTCs showed the wild type p53 sequence; a pool of 14 CTCs isolated from the same patient also showed TP53 R110 delC mutation. In the tumor breast tissue of this patient, only the TP53 R110 delG mutation was detected. In the second patient a TP53 R110 delC mutation was detected in the chest wall skin biopsy; from the peripheral blood of this patient, 5 single CTC and 6 clusters of 2 to 6 CTCs were isolated; 3 of the 5 single CTCs showed the TP53 R110 delC mutation and 2 CTCs showed the wild type TP53 allele; from the clusters, 5 showed the TP53 R110 delC mutation, and 1 cluster the wild type TP53 allele. Single white blood cells isolated as controls from both patients only showed the wild type TP53 allele. CONCLUSIONS: We are able to isolate uncontaminated CTCs and achieve single cell molecular analysis. Our studies showed the presence of different CTC sub-clones in patients with metastatic breast cancer. Some CTCs had the same TP53 mutation as their matching tumor samples although others showed either a different TP53 mutation or the wild type allele. Our results indicate that CTCs could represent a non-invasive source of cancer cells from which to determine genetic markers of the disease progression and potential therapeutic targets

Surface Plasmon Resonance Assay for Label-Free and Selective Detection of Xylella Fastidiosa

Xylella fastidiosa is among the most dangerous plant bacteria worldwide causing a variety of diseases, with huge economic impact on agriculture and environment. A surveillance tool, ensuring the highest possible sensitivity enabling the early detection of X. fastidiosa outbreaks, would be of paramount importance. So far, a variety of plant pathogen biomarkers are studied by means of surface plasmon resonance (SPR). Herein, multiparameter SPR (MP-SPR) is used for the first time to develop a reliable and label-free detection method for X. fastidiosa. The real-time monitoring of the bioaffinity reactions is provided as well. Selectivity is guaranteed by biofunctionalizing the gold transducing interface with polyclonal antibodies for X. fastidiosa and it is assessed by means of a negative control experiment involving the nonbinding Paraburkholderia phytofirmans bacterium strain PsJN. Limit of detection of 105 CFU mL 1 is achieved by transducing the direct interaction between the bacterium and its affinity antibody. Moreover, the binding affinity between polyclonal antibodies and X. fastidiosa bacteria is also evaluated, returning an affinity constant of 3.5   107m 1, comparable with those given in the literature for bacteria detection against affinity antibodies

Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report

Background: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot–Marie–Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients. Case presentation: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30&nbsp;months. Conclusions: Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes

CAT25 defines microsatellite instability in colorectal cancer by high-resolution melting PCR

Background: CAT25 (T25mononucleotide repeat of the Caspase 2 gene), is a promising DNA marker for detecting microsatellite instability (MSI) in colorectal cancer. CAT25 has the potential to be incorporated into the Bethesda panel, a commonly used panel of DNA microsatellites, or replace it in its entirety. We aimed to develop and validate a high-resolution melting-PCR (HRM-PCR) method for CAT25 instability detection in clinical samples. Methods: The instability of CAT25, BAT25 (a poly(A) tract occurring in c‐kit) and BAT26 (a poly(A) tract localized in hMSH2) microsatellites were assessed in DNA from tumour and peripheral blood obtained from 110 patients with colorectal cancer using HRM-PCR and capillary electrophoresis. Immunohistochemistry (IHC) staining for MSH2, MSH6, MLH1, and PMS2 enzymes was performed on tumours with jigj MSI. Allelic size variation of CAT25 was analysed on peripheral blood DNA from 208 healthy volunteers. Results: The HRM-PCR for CAT25 was validated in clinical samples. CAT25 showed a tight range of 64–66 base pairs. Of 110 tumours, 11 had High MSI, later confirmed by IHC. CAT25 defines MSI alone as well as when used together with BAT25 and BAT26. CAT25 results provided 100% predictive values and p < 0.0001 to classify a tumour as having high MSI. Conclusions: We developed and validated a new HRM-PCR assay to detect CAT25 instability. Our findings showed a limited allelic size variation of CAT25 and highlighted to CAT25 as a promising marker for MSI analysis.Fil: Sánchez, A.G.. Hospital Privado Universitario de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Juaneda, I.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Eynard, H.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Basquiera, Ana Lisa. Hospital Privado Universitario de Córdoba; ArgentinaFil: Palazzo, E.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Calafat, P.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Palla, V.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Romagnoli, Pablo Alberto. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Alvarellos, T.. Hospital Privado Universitario de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin