B cell autoimmunity and bone damage in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease associated with significant bone damage. Pathological bone remodeling in RA is primarily driven by persistent inflammation. Indeed, pro-inflammatory cytokines stimulate the differentiation of bone-resorbing osteoclasts and, in parallel, suppress osteoblast function, resulting in net loss of bone. Abating disease activity thus remains the major goal of any treatment strategy in patients with RA. Autoantibody-positive patients, however, often show a rapidly progressive destructive course of the disease, disproportionate to the level of inflammation. The epidemiological association between RA-specific autoantibodies, in particular anti-citrullinated protein autoantibodies, and poor structural outcomes has recently found mechanistic explanation in the multiple roles that B cells play in bone remodeling. In this review, we will summarize the substantial progress that has been made in deciphering how B cells and autoantibodies negatively impact on bone in the course of RA, through both inflammation-dependent and independent mechanisms

Spectral emissivity and temperature maps of the Solfatara crater from DAIS hyperspectral images

Quantitative maps of surface temperature and spectral emissivity have been retrieved on the Solfatara crater at Pozzuoli (Naples) from remote sensing hyperspectral data. The present study relies on thermal infrared images collected on July 27, 1997 by the DAIS hyperspectral sensor, owned by the German aerospace center (DLR). The Emissivity Spectrum Normalization method was used to make temperature and emissivity estimates. Raw data were previously transformed in radiance and corrected for the atmospheric contributes using the MODTRAN radiative transfer code and the sensor response functions. During the DAIS flight a radiosonde was launched to collect the atmospheric profiles of pressure, temperature and humidity used as input to the code. Retrieved temperature values are in good agreement with temperature measures performed in situ during the campaign. The spectral emissivity map was used to classify the image in different geomineralogical units with the Spectral Angle Mapper method. Areas of geologic interest were previously selected using a mask obtained from an NDVI image calculated with two channels of the visible (red) and the near infrared respectively

The gamma-ray burst monitor for Lobster-ISS

Lobster-ISS is an X-ray all-sky monitor experiment selected by ESA two years ago for a Phase A study (now almost completed) for a future flight (2009) aboard the Columbus Exposed Payload Facility of the International Space Station. The main instrument, based on MCP optics with Lobster-eye geometry, has an energy passband from 0.1 to 3.5 keV, an unprecedented daily sensitivity of 2x10^{-12} erg cm^{-2}s$^{-1}, and it is capable to scan, during each orbit, the entire sky with an angular resolution of 4--6 arcmin. This X-ray telescope is flanked by a Gamma Ray Burst Monitor, with the minimum requirement of recognizing true GRBs from other transient events. In this paper we describe the GRBM. In addition to the minimum requirement, the instrument proposed is capable to roughly localize GRBs which occur in the Lobster FOV (162x22.5 degrees) and to significantly extend the scientific capabilities of the main instrument for the study of GRBs and X-ray transients. The combination of the two instruments will allow an unprecedented spectral coverage (from 0.1 up to 300/700 keV) for a sensitive study of the GRB prompt emission in the passband where GRBs and X-Ray Flashes emit most of their energy. The low-energy spectral band (0.1-10 keV) is of key importance for the study of the GRB environment and the search of transient absorption and emission features from GRBs, both goals being crucial for unveiling the GRB phenomenon. The entire energy band of Lobster-ISS is not covered by either the Swift satellite or other GRB missions foreseen in the next decade.Comment: 6 pages, 4 figures. Paper presented at the COSPAR 2004 General Assembly (Paris), accepted for publication in Advances in Space Research in June 2005 and available on-line at the Journal site (http://www.sciencedirect.com/science/journal/02731177), section "Articles in press

Diginyc partial hydatidiform mole with increased fetal nuchal translucency and ovarian hyperstimulation syndrome.

PURPOSE OF INVESTIGATION Hydatidiform mole (HM) is an abnormal pregnancy characterized by proliferation of cytotrophoblast and syncytiotrophoblast and vesicular swelling of placental villi. The fetus or embryo can be absent or abnormal. HMs can be complete or partial. CASE REPORT A case of diginyc partial HM at 12 weeks of gestational age was referred to the present center of prenatal diagnosis. The patient showed ovarian hyperstimulation syndrome. At ultrasonography, increased fetal nuchal translucency (NT) with fetal anomaly was evident, without sonographic signs of placental mole. Pregnancy was terminated with legal abortion. RESULTS Partial HM (PHM) was suspected by ultrasonographic fetal markers with ovarian hyperstimulation syndrome, but the diagnosis was performed only with fluorescent in situ hybridization. In particular fetal NT appeared increased also in diginyc mole. CONCLUSION In order to improve the detection rate of PHM, routine histological examinations may be associated to fluorescent in situ hybridization in all cases of fetal anomalies

A fast and accurate energy source emulator for wireless sensor networks

The capability to either minimize energy consumption in battery-operated devices, or to adequately exploit energy harvesting from various ambient sources, is central to the development and engineering of energy-neutral wireless sensor networks. However, the design of effective networked embedded systems targeting unlimited lifetime poses several challenges at different architectural levels. In particular, the heterogeneity, the variability, and the unpredictability of many energy sources, combined to changes in energy required by powered devices, make it difficult to obtain reproducible testing conditions, thus prompting the need of novel solutions addressing these issues. This paper introduces a novel embedded hardware-software solution aimed at emulating a wide spectrum of energy sources usually exploited to power sensor networks motes. The proposed system consists of a modular architecture featuring small factor form, low power requirements, and limited cost. An extensive experimental characterization confirms the validity of the embedded emulator in terms of flexibility, accuracy, and latency while a case study about the emulation of a lithium battery shows that the hardware-software platform does not introduce any measurable reduction of the accuracy of the model. The presented solution represents therefore a convenient solution for testing large-scale testbeds under realistic energy supply scenarios for wireless sensor networks

Performance Evaluation of Components Using a Granularity-based Interface Between Real-Time Calculus and Timed Automata

To analyze complex and heterogeneous real-time embedded systems, recent works have proposed interface techniques between real-time calculus (RTC) and timed automata (TA), in order to take advantage of the strengths of each technique for analyzing various components. But the time to analyze a state-based component modeled by TA may be prohibitively high, due to the state space explosion problem. In this paper, we propose a framework of granularity-based interfacing to speed up the analysis of a TA modeled component. First, we abstract fine models to work with event streams at coarse granularity. We perform analysis of the component at multiple coarse granularities and then based on RTC theory, we derive lower and upper bounds on arrival patterns of the fine output streams using the causality closure algorithm. Our framework can help to achieve tradeoffs between precision and analysis time.Comment: QAPL 201

Vitamin D 25OH Deficiency and Mortality in Moderate to Severe COVID-19: A Multi-Center Prospective Observational Study

Introduction: Several studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19. Method: This prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (<20 ng/mL) or adequate (≥20 ng/mL). We built a propensity score for low/adequate vitamin D 25OH levels to balance the clinical and demographic properties of the cohort, which resulted in 261 patients with good common support used for the survival analysis. Results: Two Hundred-seventy-seven (77%) of the 361 enrolled patients (207 [57%] males, median age 73 ± 15.6 years) had vitamin D 25OH deficiency. Fifty-two (20%) of the 261 matched patients died during the hospital stay, corresponding to a hazard ratio of 1.18 for vitamin D 25OH deficiency (95% confidence interval: 0.86–1.62; p = 0.29). Discussion: The prevalence of vitamin D 25OH deficiency was confirmed to be very high in hospitalized patients with COVID-19. The use of a propensity score demonstrate an absence of significant association between vitamin D deficiency and mortality in hospitalized patients

Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis

BACKGROUND: Autoantibodies such as anti-citrullinated protein antibodies (ACPA) are major risk factors for articular bone destruction from the earliest phases of rheumatoid arthritis (RA). The aim of the current study was to determine whether RA-associated autoantibodies also impact on systemic bone loss in patients with early disease. METHODS: Systemic bone mineral density (BMD) was measured in the lumbar spine and the hip in 155 consecutive treatment-na\uefve patients with early RA (median symptom duration 13 weeks). Demographic and disease-specific parameters, including clinical disease activity, ultrasonographic (US) examination of the hands and wrists, radiographic scoring of joint damage, ACPA and rheumatoid factor (RF) levels were recorded from all patients. Reduced BMD was defined as Z score\u2009 64\u2009-1 SD and analysed in relation to disease-related characteristics and autoantibody subgroups. RESULTS: Reduced BMD was found in 25.5 % of the patients in the spine and 19.4 % in the hip. Symptom duration, clinical and US disease activity, functional disability and radiographic damage did not significantly impact on spine and hip BMD loss in regression analyses adjusted for possible confounders (age, gender, menopausal status, current smoking, body mass index). In contrast, ACPA positivity (at any level) negatively affected the spine Z-score (adjusted OR (95 % CI) 2.76 (1.19 to 6.42)); the hip Z score was affected by high titres only (adjusted OR (95 % CI) 2.96 (1.15 to 7.66)). The association of ACPA with reduced BMD in the spine was confirmed even at low levels of RF (adjusted OR (95 % CI) 2.65 (1.01 to 7.24)), but was further increased by concomitant high RF (adjusted OR (95 % CI) 3.38 (1.11 to 10.34)). In contrast, Z scores in the hip were significantly reduced only in association with high ACPA and RF (adjusted OR (95 % CI) 4.96 (1.48 to 16.64)). CONCLUSIONS: Systemic BMD in patients with early RA is reduced in relation with ACPA positivity and high RF levels. This finding supports the notion that RA-associated autoimmunity may have a direct causative role in bone remodeling

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study

To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction

Clinical consequences of BRCA2 hypomorphism

Altres ajuts: Asociación Española contra el Cáncer (LABAE16020PORTT)Altres ajuts: Asociación Española contra el Cáncer (ERAPERMED2019-215)The tumor suppressor FANCD1/BRCA2 is crucial for DNA homologous recombination repair (HRR). BRCA2 biallelic pathogenic variants result in a severe form of Fanconi anemia (FA) syndrome, whereas monoallelic pathogenic variants cause mainly hereditary breast and ovarian cancer predisposition. For decades, the co-occurrence in trans with a clearly pathogenic variant led to assume that the other allele was benign. However, here we show a patient with biallelic BRCA2 (c.1813dup and c.7796 A > G) diagnosed at age 33 with FA after a hypertoxic reaction to chemotherapy during breast cancer treatment. After DNA damage, patient cells displayed intermediate chromosome fragility, reduced survival, cell cycle defects, and significantly decreased RAD51 foci formation. With a newly developed cell-based flow cytometric assay, we measured single BRCA2 allele contributions to HRR, and found that expression of the missense allele in a BRCA2 KO cellular background partially recovered HRR activity. Our data suggest that a hypomorphic BRCA2 allele retaining 37-54% of normal HRR function can prevent FA clinical phenotype, but not the early onset of breast cancer and severe hypersensitivity to chemotherapy