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International audience; This paper describes first results obtained from the SWIM (Surface Waves Investigation and Monitoring) instrument carried by CFOSAT (China France Oceanography Satellite), which was launched on October 29th, 2018. SWIM is a Ku-Band radar with a near-nadir scanning beam geometry. It was designed to measure the spectral properties of surface ocean waves. First, the good behavior of the instrument is illustrated. It is then shown that the nadir products (significant wave height, normalized radar cross-section and wind speed) exhibit an accuracy similar to standard altimeter missions, thanks to a new retracking algorithm, which compensates a lower sampling rate compared to standard altimetry missions. The off-nadir beam observations are analyzed in details. The normalized radar cross-section varies with incidence and wind speed as expected from previous studies presented in the literature. We illustrate that, in order to retrieve the wave spectra from the radar backscattering fluctuations, it is crucial to apply a speckle correction derived from the observations. Directional spectra of ocean waves and their mean parameters are then compared to wave model data at the global scale and to in situ data from a selection of case studies. The good efficiency of SWIM to provide the spectral properties of ocean waves in the wavelength range [70m-500m] is illustrated. The main limitations are discussed, and the perspectives to improve data quality are presented.

This study explored process synergies attainable by integrating a vacuum ultraviolet-based advanced oxidation process with biofiltration. A comparison using granular activated carbon or granular zeolite as filtration media were examined in context of advanced wastewater treatment for potable reuse. Six biofiltration columns, three with granular activated carbon and three with granular zeolite, were operated in parallel and batch-fed daily with nitrified secondary effluent. After achieving a pseudo-steady state through the filter columns, vacuum ultraviolet treatment was applied as pre-treatment or as post-treatment, at two different applied energies (i.e., VUV-E1=1 kWh/m3 and VUV-E10=10 kWh/m3). Once granular activated carbon had transitioned to biologically activated carbon, as determined based on soluble chemical oxygen demand removal, adsorption was still observed as the main mechanism for contaminants of emerging concern and nitrate removal. Vacuum ultraviolet pre-treatment markedly improved contaminants of emerging concern removal through the integrated system, achieving 40% at VUV-E1 and 90% at VUV-E10. When applied as post-treatment to zeolite column effluents, VUV-E1 and VUV-E10 further increased contaminants of emerging concern removal by 20% and 90%, respectively. In the zeolite system, vacuum ultraviolet pre-treatment also increased soluble chemical oxygen demand removal efficiency, indicating that higher energy vacuum ultraviolet increased biodegradability. Total prokaryotes were two-fold more abundant in biologically activated carbon than in zeolite, with vacuum ultraviolet pretreatment markedly affecting microbial diversity, both in terms of richness and composition. Media type only marginally affected microbial richness in the biofilters but showed a marked impact on structural composition. No clear relationship between compositional structure and depth was observed.

Brain structural bases of individual differences in attachment are not yet fully clarified. Given the evidence of relevant cerebellar contribution to cognitive, affective, and social functions, the present research was aimed at investigating potential associations between attachment dimensions (through the Attachment Style Questionnaire, ASQ) and cerebellar macro- and micro-structural measures (Volumetric and Diffusion Tensor Imaging data). In a sample of 79 healthy subjects, cerebellar and neocortical volumetric data were correlated with ASQ scores at the voxel level within specific Regions Of Interest. Also, correlations between ASQ scores and age, years of education, anxiety and depression levels were performed to control for the effects of sociodemographic and psychological variables on neuroimaging results.Positive associations between scores of the Preoccupation with Relationships (ASQ subscale associated to insecure/anxious attachment) and cortical volume were found in the cerebellum (right lobule VI and left Crus 2) and neocortex (right medial OrbitoFrontal Cortex, OFC) regions. Cerebellar contribution to the attachment behavioral system reflects the more general cerebellar engagement in the regulation of emotional and social behaviors. Cerebellar properties of timing, prediction, and learning well integrate with OFC processing supporting the regulation of attachment experiences. Cerebellar areas might be rightfully included in the attachment behavioral system.

Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippocampal volumes would be associated with worse upper-limb sensorimotor impairment.Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke (>180 days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, interquartile range = 18, range = 23-93; 135 women and 222 men). Sensorimotor impairment was estimated from the Fugl-Meyer Assessment of Upper Extremity scores. Robust mixed-effects linear models were used to test associations between post-stroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, p-value < 0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. We also performed an exploratory analysis to test whether sex differences influence the relationship between sensorimotor impairment and hippocampal volume.Upper limb sensorimotor impairment was positively associated with ipsilesional (p = 0.005; d = 0.33) but not contralesional (p = 0.96; d = 0.01) hippocampal volume, such that impairment was worse for participants with smaller ipsilesional hippocampal volume. This association remained significant independent of lesion volume or other covariates (p = 0.001; d = 0.36). Evidence indicates an interaction between sensorimotor impairment and sex for both ipsilesional (p = 0.008; d = −0.29) and contralesional (p = 0.006; d = −0.30) hippocampal volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippocampal volumes compared to men.The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippocampal volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippocampal volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.

The purpose of this paper is to accompany the release of the Jason-3 GDR-F products delivered as part of the GDR-F reprocessing campaign and to explain its main benefits for the users of altimetry products. This reprocessing campaign has a twofold objective: improve the quality of the products and share common standards with Sentinel-6/Jason-CS. Illustrations of the different benefits for the users of altimetry products are provided.

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).

The accuracy of sea surface parameters retrieved from altimeter missions is predominantly governed by the choice of the so-called ``retracking'' algorithm, i.e., the model and inversion method implemented to obtain the surface parameters from the backscattered waveform. For continuity reasons, the choice of space agencies is usually to apply the same retracker from one satellite mission to the other to ensure long-time homogeneous series. In this article, taking the opportunity of a new configuration of the nadir pointing measurements onboard the recently launched China France Oceanography Satellite (CFOSAT) with the Surface Waves Investigation and Monitoring (SWIM) instrument (Hauser et al., 2020), the retracking method was upgraded, by implementing a novel algorithm, called ``Adaptive'' retracker. It combines the improvements brought by Poisson et al., (2018) for the estimation of surface parameters from peaked waveforms over sea ice, improvements in the way the instrumental characteristics are considered in the model (mispointing, point target response) and a more accurate consideration of speckle statistics. In this article, we first show from simulations carried out in the instrumental configuration of SWIM that the Adaptive algorithm has better accuracy and performance than the classical MLE4 algorithm. Then, the geophysical parameters obtained with real data from SWIM are analyzed with comparisons to reference data sets (model and products from altimeters). We show that this new algorithm has several benefits with respect to the classical MLE4 method: no need of lookup tables to correct biases, significant noise reduction on all geophysical variables especially the significant wave height, and performance of inversion over a large set of echo shapes, resulting from standard oceanic scenes as well as highly specular conditions such as over bloom or sea ice.

International audience; The Chinese-French oceanography satellite, CFOSAT, was launched on October 2018. Two Ku-band scatterometers are on-board: SCAT for the wind observation and SWIM for the wave observation. This paper presents the most recent results on the SWIM data quality analysis a few months after the end of the CAL/VAL phase.

Il suinetto da latte arrosto è un piatto tradizionale della Sardegna ampiamente consumato in tutta l’isola e molto apprezzato dai turisti. Purtroppo, a causa della recrudescenza della peste suina africana (PSA) nell’isola, è stata vietata l’esportazione di carni suine fresche e/o prodotti derivati. Alcune precauzioni necessarie per ottenere il permesso di esportare i prodotti a base di carne di maiale sono contenute nel provvedimento attuativo del Programma straordinario di eradicazione della PSA 2015-2017 emanato dal Governo Regionale. Una di queste consiste nel trattamento termico di precottura della carne fino al raggiungimento di una temperatura di 80 °C in tutta la massa. L’esportazione della carne di maiale rappresenta un’importante opportunità economica per gli operatori sardi del settore, fortemente interessati alla dimostrazione dell’efficacia e applicabilità del trattamento termico per garantire la sicurezza e la qualità dei loro prodotti. Lo scopo di questo studio era quello di valutare, mensilmente, da 0 a 150 giorni, la shelf-life dei campioni di carne trattati termicamente e conservati sottovuoto a 4 °C. Pertanto, cinque mezzene di suinetto, per punto di campionamento, sono state analizzate da un punto di vista microbiologico (conta di batteri patogeni e dannosi) e chimico (perossidazione lipidica), prima del completamento della cottura. Dopo 40 min in forno a 210 °C, è stato eseguito test di accettabilità sensoriale, per valutare il gradimento dei consumatori. I risultati ottenuti consentono di concludere che, la contaminazione microbica post-processo non ha determinato un decadimento della qualità e dell’accettabilità sensoriale del prodotto, fino a 150 giorni di shelf-life. I risultati evidenziano la necessità di prendere in considerazione l’applicazione di un trattamento post-letale per ridurre la contaminazione microbica.

A comprehensive pilot study was carried out to experimentally assess the potential of newly developed treatment trains integrating two-stage AOPs and biofiltration to reach potable reuse water quality standards from municipal wastewater. The processes consisted of a two-stage AOPs with (carbon or limestone) biofiltration, the first AOP (O-3/H2O2) serving as pre-treatment to biofiltration and the second AOP (UV254/H2O2) serving as post-biofiltration finishing step to ensure advanced disinfection. A comprehensive monitoring campaign was put in place resulting from the combination of targeted, nontargeted and suspect screening measurements. It was found that 13 organic micropollutants were detected from a list of 219 suspects although at ng/L level only. For the treatment conditions piloted in this study (O-3=13 +/- 0.5 mg/L H2O2 = 11 +/- 0.4 mg/L for the O-3/H(2)O(2 )process, and UV = 410 +/- 63.5 mJ/cm(2), H2O2= 5 mg/l for the UV254/H(2)O(2 )process), it was possible to estimate the overall removal efficacy for each unit process, which was found to follow this order: RO (99%) > BAC (87%) > O-3-H2O2(78%) > BAL (67%) > UV/H2O2(43%) > AOP contact chamber (19%) > UF(0%), with the treatment train integrating two AOPs and granular biofiltration with activated carbon (O-3/H2O2+ BAC + UV254/H2O2) showing superior performance with a 99% abatement in total micropollutants. No ecotoxicologically-positive response was generally observed for any of the effluent samples from the tested trains, even when pre-concentration factors up to 100-1000 times were employed to increase the sensitivity of the bioassay methods.

A comprehensive pilot study was carried out to experimentally assess the potential of newly developed treatment trains integrating two-stage AOPs and biofiltration to reach potable reuse water quality standards from municipal wastewater. The processes consisted of a two-stage AOPs with (carbon or limestone) biofiltration, the first AOP (O

Purpose To optimize a three-phase CTU in order to obtain the best trade-off between image quality and radiation dose. Methods and materials Considering the increase in CT examinations in our hospital, a high dose clinical protocols optimization program was undertaken. A CTU protocol was optimized, with 128-slice Siemens tomography, with CareDose4D for the real-time mA modulation. Starting from a retrospective analysis of a cohort of 43 patients (medium weight 66,9 kg), in terms of CTDIvol and SSDE (Size Specific Dose Estimates), we obtained a mean total effective dose of 26,7 mSv (estimated with CTExpo V2.0). Analyzing each protocol phase we realized to have a high margin to reduce dose. Taking as starting point AAPM indications [1] we identified a set of candidate protocols and used them for Catphan 600 Phantom acquisitions, all with automatic dose modulation and different mAs ref options. The quality reference mAs ref represents the effective mAs (mA x rotation time/pitch) value suitable for an average-sized patient weighing 70–80 kg. We analyzed image quality of the scans in terms of noise, spatial resolution and low contrast, and then we chose the protocol to be clinically validated. Finally we made a prospective analysis of 18 patients (medium weight 66,4 kg), again in terms of CTDIvol, SSDE and effective dose. Results Among all phantom acquisitions we chose a protocol with a noise decrease of 11% and a minimal loss of contrast (0,09% on 3 mm detail). The MTF50 value passes from 3,21 lp/mm to 3,08 lp/mm. The main radiological parameters of the protocol are summarized in the table below (gray for old protocol, white for the new one). The mean effective dose passed from 25,7 mSv to 14,1 mSv. Conclusions It was possible to reduce the dose by 45% without affecting the image quality.

Contains fulltext : 193179.pdf (Publisher’s version ) (Open Access) The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Early tokamaks with circular cross-section plasmas were vertically stable in nature and no problems were reported on the control of the vertical position. However, the concept of vertically elongated plasma cross-section, with benefits to the energy confinement time, led to vertical instabilities. To overcome this problem, complex closed feedback loop control systems with a vertical position measurement, signal processing, control algorithm, power supplies and active actuating coils are used. The Tokamak a Configuration Variable (TCV) permits the stabilization of highly elongated plasmas, with a powerful vertical position control system and fast power supplies capable of response times under 0.1 ms. The introduction of the new Advanced Plasma Control System (APCS) in TCV has required the development of a new vertical position observer built to optimally exploit the capabilities of the new system and correct for the changes that were detected by the introduction of signal digitizing in the feedback loop. This paper discusses the need for a new measurement of the plasma vertical position, the method to build the observer and the validation of the measured position by comparing with previous methods and observers. A summary of the ongoing work is provided. We also discuss its aim and the goals that are expected to be achieved by exploring the new digital non-linear control algorithm capabilities of APCS.

A set of 24 saddle loops is used on the Tokamak a Configuration Variable (TCV) to measure the radial magnetic flux at different toroidal and vertical positions. The new system is calibrated together with the standard magnetic diagnostics on TCV. Based on the results of this calibration, the effective current in the poloidal field coils and their position is computed. These corrections are then used to compute the distribution of the error field inside the vacuum vessel for a typical TCV discharge. Since the saddle loops measure the magnetic flux at different toroidal positions, the non-axisymmetric error field is also estimated and correlated to a shift or a tilt of the poloidal field coils.

A second order null divertor (snowflake) has been successfully created and controlled in the TCV Tokamak. The results of ideal MHD edge stability computations show an enhancement of the edge stability properties of the snowflake equilibria compared to standard X-point configurations....

Objectives: Stem cell therapies based on differentiation of adult or embryonic stem cells into specialized ones appear to be effective for treating several human diseases. This work addresses the mathematical simulation of proliferation kinetics of stem cells. Materials and methods: Sheep bone marrow mesenchymal stem cells (phenotype characterized by flow cytometry analysis) seeded at different initial concentrations in Petri dishes were expanded to confluence. Sigmoid temporal profiles of total counts obtained through classic haemocytometry were quantitatively interpreted by both a phenomenological logistic equation and a novel model based on a one-dimensional, single-staged population balance approach capable of taking into account contact inhibition at confluence. The models’ parameters were determined by comparison with experimental data on population expansion starting from single seeding concentration. Reliability of the models was tested by predicting cell proliferation carried out starting from different seeding concentrations. Results and discussion: It was found that the proposed population balance modelling approach was successful in predicting the experimental data over the whole range of initial cell numbers investigated, while prediction capability of phenomenological logistic equation was more limited.

Although field studies have found porcine reproductive and respiratory syndrome (PRRSV) inactivated vaccines to be beneficial in reducing losses linked to PRRSV infection, immune mechanisms induced by these vaccines need better understanding. In the study reported here, we examined the interferon-gamma(+) (IFNgamma(+)) PRRS-specific T cell responses induced after infection and vaccination with an inactivated PRRS vaccine. Autologous monocyte-derived dendritic cells loaded with the PRRSV P120 strain were used to re-stimulate ex vivo T cells that had been primed in vivo by either the virus or the vaccine, or both. Virus-specific IFNgamma(+) T cells were quantified by using a porcine IFNgamma- ELISpot assay. A specific but low live virus-induced response was observed between days 35 and 70 for most of the pigs tested, while a significant inactivated vaccine-induced PRRSV-specific IFNgamma(+) T-cell response was measured soon after vaccination. Moreover, we observed that vaccination of pre-challenged pigs clearly favoured the PRRSV-specific cell-mediated immunity primed by the live virus. To characterize further the nature of the PRRSV-specific T cells, the different T-cell subsets involved in PRRSV immunity were analyzed by flow cytometry. We showed that the inactivated vaccine was able to prime both CD4(+)CD8(int+) and CD8(high) virus-specific T cells and that CD4(+)CD8(int+) were preferentially recalled by the live virus.

The aim of this study was to investigate whether COL5A1 rs12722 polymorphism is associated with musculoskeletal injuries in elite soccer players.Fifty-four male professional soccer players of European origin (25.9±4.3 years) were recruited from a team participating at the Official Italian Professional Championship during four consecutive seasons (2009-2013). The incidence and severity of musculoskeletal injuries and its relationship to COL5A1 rs12722 polymorphism were analyzed. DNA was extracted from buccal swab. The cohort was genotyped for the COL5A1 rs12722 single nucleotide polymorphism (SNP) through PCR and enzyme digestion with BstUI, and musculoskeletal injuries data were collected during the four seasons. Injuries were categorized under 5 degrees of severity based on the number of days' absence, while musculoskeletal injuries incidence was calculated per 1,000 hours of exposure to training and matches ((∑ injuries/∑ exposure hours) x 1000).No significant differences were found among genotypes for incidence of musculoskeletal injuries (P=0.683). Participants with TT genotype (3.71±0.5, N.=4) showed a trend (P=0.193) versus an higher severity of injuries than individuals with TC (2.98±0.8, N.=10) or CC (2.75±0.95, n=4) genotypes. The COL5A1 rs12722 accounted for 44% of severity of injuries (P=0.002).In conclusion, the COL5A1 rs12722 was found to be associated with severity of musculoskeletal injuries but not with incidence of musculoskeletal injuries in top-level soccer players.

International audience; Stroke is the second single highest cause of death in Europe. The low reliability of animal models in replicating the human disease is one of the most serious problems in the field of medical and pharmaceutical research about stroke. The standard models for the study of ischemic stroke are often poorly predictive as they simulate only partially the human disease. This work aims at investigating animal models with diseases typically associated with the onset of stroke in human patients. We have designed and realised a knowledge base for collecting, elaborating, and extracting analytical results of genomic, pro-teomic, biochemical, morphological investigations from animal models of cerebral stroke. Data analysis techniques are tailored to make the data available for processing and correlation, in order to increase the predictive value of the preclinical data, to perform biosimulation studies, and to support both academic and industrial research in the area of cerebral stroke therapy. A first statistical analysis of the retrieved information leads to the validation of our animal models and suggests a predictive and translational value for parameters related to a specific model. In particular, concerning gene expression data, we have applied a data analysis pipeline that initially takes into account an initial set of 64,000 genes and brings down the focus on a few tens of them.

Memory impairment is a common consequence of neurological injury or disease, causing significant disability in everyday life, and is therefore a critical target for rehabilitation intervention. Here we report a review of the available evidence on the efficacy of restitution-oriented therapies and compensatory approaches for memory rehabilitation. A total of 110 studies was systematically classified and analyzed in order to generate evidence-based clinical recommendations for treatment providers. Different key aspects, such as types of brain damage, treatments characteristics and outcome measurements guided the evaluation of the literature as to appraise the potential interaction between patients characteristics, interventions and outcomes. The general conclusion is that memory re-training programs and compensatory approaches are probably effective in ameliorating memory disorders in patients with focal brain lesions, with some evidences of changes in memory functioning extending beyond the trained skills. Externally directed assistive devices and specific learning strategies are effective (with a level D and B of evidence, respectively) in retaining information relevant for daily needs also in patients with degenerative diseases. Some methodological concerns, such as the heterogeneity of subjects, interventions and outcomes studied, may limit the generalization of the present recommendations.

An edge-localized mode (ELM) H-mode regime, supported by electron cyclotron heating, has been successfully established in a “snowflake” (second-order null) divertor configuration for the first time in the TCV tokamak. This regime exhibits 2 to 3 times lower ELM frequency and 20%–30% increased normalized ELM energy ($Delta W_{ELM}/W_p$) compared to an identically shaped, conventional single-null diverted H mode. Enhanced stability of mid- to high-toroidal-mode-number ideal modes is consistent with the different snowflake ELM phenomenology. The capability of the snowflake to redistribute the edge power on the additional strike points has been confirmed experimentally.

A Horse Is a Horse, of Course The history of horse domestication is closely tied to the history of the human society. Wade et al. (p. 865 ) report on the sequencing and provide a single nucleotide polymorphism map of the horse ( Equus caballus ) genome. Horses are a member of the order perissodactyla (odd-toed animals with hooves). The analysis reveals an evolutionarily new centromere on equine chromosome 11 that displays properties of an immature but fully functioning centromere and is devoid of centromeric satellite sequence. The findings clarify the nature of genetic diversity within and across horse breeds and suggest that the horse was domesticated from a relatively large number of females, but few males.

The Ogliastra Project is a large genetic and epidemiologic population-based study aiming at dissecting complex diseases and carried out in ten isolated villages of Ogliastra region, in eastern Sardinia. Ogliastra consists of 23 small villages with a mean number of inhabitants of about 1500, and with characteristics of genetic isolates. Key features of its population are ancient origins, few founders, a centenarian geographical isolation, a slow demographical growth with scarce immigration, high endogamy and consanguinity[1]. Study design has started as cross-sectional, but thanks to the great enthusiasm and collaboration of the population it evolved in a longitudinal one. Phase I of the epidemiological survey took place between December 2001 and October 2008, collecting data on 11189 people. Cohort recruitment was accomplished through information campaigns and letters sent to every family. Enrolled people, ranging in age from 2 to 104 years, first gave their informed consent and a blood sample for DNA extraction and determination of about 50 serological and haematological parameters. Subsequently, they underwent an extensive evaluation comprehensive of anthropometrical and blood pressure measurements, bioelectrical impedance for body composition assessment, and quantitative ultrasonography for bone mass screening. A structured interview was administered by trained physicians in order to collect socio-demographic data, living habits, exposure to most common risk factors, medical and medication history, information about familial disorders and a physical examination. Here we present results of prevalence studies on some of the pathologies investigated in the Ogliastra Project. Androgenetic alopecia was diagnosed taking grade II vertex of Norwood scale in men and grade III of Ludwig scale in women as cut-offs. Hypertensive status was determined applying the guidelines of European Society of Hypertension (systolic BP>140 mmHg, diastolic BP> 90 mmHg or antihypertensive treatment). The T-score threshold for Amplitude Dependent Speed of Sound of -3.2 SD was used to diagnose osteoporosis. Metabolic syndrome was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III criteria, while obesity was based on the World Health Organization definition (BMI ?30 kg/m2). In Ogliastra as a whole prevalence of androgenetic alopecia is 44.4% in men (I.C. 95%: 42.9% - 45.7%) and 1% in women (0.0% - 2.1%); hypertension prevalence is 43.5% in men (42.1% - 44.8%) and 34.3% in women (33.3% - 35.4%); osteoporosis prevalence is 17.1% in women (14.9% - 18.8%) and 5.5% in men (3.6% - 7.4%); finally metabolic syndrome prevalence is 19.6% (18.8% - 20.4%) and obesity prevalence is 16.4% (15.7% - 17.2%) in both men and women. Significant differences observed among some of the villages (fig. 1) may reflect different genetic background we intend to investigate.

In this paper a few relationships between a Decomposition Structure and its Incidence Coalgebra and Algebra are studied. In particular, some results about the so-called Isomorphism Problem for Incidence Algebras of Moebius Categories are generalized. Moreover, we determine conditions under which all endomorphisms and derivations of an Incidence Algebra are continuous with respect to the finite topology.

p16INK4a and p53 are tumor-suppressor genes frequently altered in various malignancies, including cutaneous melanoma. The purpose of the study was to establish the prognostic value of immunohistochemical expression of p16INK4a a and p53 in sporadic cutaneous melanoma (CM) in two regions with a high-risk for melanoma in Italy and Ecuador. Immunohistochemical staining of p16 and p53 was performed in samples of primary CM from 82 patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Survival differences between categories of p16 or p53 expression were analyzed using the product-limit procedure (Kaplan-Meier method, log-rank test). Clinical variables (gender, age, tumor location, Clark's level, thickness) were correlated with survival and p16 or p53 expression. p16 nuclear immunoreactivity was observed in 85% of Italian patients compared to 48.7% of Ecuadorians; a small number of cases showed p53 immunoreactivity in both populations. Only nuclear p16 expression exhibited a significant correlation with survival (Italians p=0.001, Ecuadorians p=0.017) but did not appear to correlate with any clinicopathological parameter. No significant difference was observed in survival with regard to p53 expression or cytoplasmic p16. Our results demonstrate that nuclear expression of p16 can be considered a molecular prognostic factor in patients with sporadic CM and indicate its importance as a clinical marker.

As part of the Ogliastra project, which focuses on the study of the genealogy, genetics and clinical features of isolated populations in this area of Sardinia, we conducted a transversal epidemiological study to estimate the prevalence, the environmental determinants and heredibility of osteoporosis in Baunei (n=3800). This village has historically been geographically isolated, and this is seen by its limited number of founders, high rate of endogamous marriages (82.04%), and low number of immigrants (3.97% before 1950). Beyond this, the population is generally attached to the traditional ways, retaining many old features of lifestyle, eating habits and behaviour. This genetic and environmental homogeneity facilitates the study of complex diseases. Participation study was voluntary: 917 women, ranging in age from 33 to 98 years old and previously informed that the study was conformed with international ethical guidelines, furnished a blood sample used for hematological and serological parameters, anthropometrical measurements, bioimpedance, Quantitative Ultrasonography (QUS) using a DBM Sonic Bone Profiler (IGEA Srl) and the structured interview to collected socio-economic, lifestyle, medical and pharmacological history and family history of osteoporosis. The main determinants of bone mass were modelled using General Linear Models. The T-score threshold for AD-SoS (Amplitude Dependent Speed of Sound) of -3.2 SD, was used to estimate the osteoporosis prevalence. The prevalence estimate was age adjusted using the general Italian population for 2005 (ISTAT). The 10 years probability of clinical vertebral fractures was calculated according to guidelines reported for diagnosis, prevention and therapy of osteoporosis (EDIMES - Pavia 2005). Using the genealogical data referred to the last 400 years and PedNavigator, a useful software able to reconstruct multigenerational pedigrres, we created 6 big families including all participants to the study; heritability estimate of QUS parameters was obtained by the variance component method implemented in the SOLAR software. The ultrasonic parameters AD-SoS and Ultrasound Bone Profile Index (UBPI) are strictly related to age and months since menopause. Multiple regression analysis detected significant association with height and alkaline phosphatase. UBPI resulted to be significantly correlated with weight, fat mass and menarche. Besides, AD-SoS and UBPI corrected for age and months since menopause, were found to be significantly associated with: hormone replacement therapy, sport activity (only AD-SoS), current or past diet (only AD-SoS), chronic use of steroids drugs, present or past chemotherapy, endocrine and gastrointestinal disorders. The prevalence of osteoporosis in baunei was 19.4 %. (95% CI: 17.0%-21.7%). The percentage of subjects with high 10 years risk of vertebrate fracture (>4%) was 4.1%. Using PedNavigator, we observed that individuals with reduced mineral bone density clustered in big families, showing that familiarity is an important risk factor for this disease. Heritability estimates of AD-SoS and UBPI, after adjusting for the associated covariates explaining more than 60% of the variability of trait variability, were found to be 30% and 64% respectively. (p

Infection of domestic cats with feline immunodeficiency virus (FIV) is associated with the development of an acquired immunodeficiency syndrome (AIDS). The pathogenesis of FIV is not fully understood but it has been reported that the immune system is progressively impaired during disease progression. As a result, anti-FIV specific immune response will usually not clear the virus and the acute stage is followed by a chronic asymptomatic phase. The overall objective of this study was to characterized FIV-induced immune cellular responses and -mediated immune disorder following the first weeks post-infection. Using both cytokine ELISpot and intracellular staining assays, FIV-specific T cells were monitored at 6, 9 and 12 weeks post-infection. We demonstrated that both IFNgamma(+) and, CD4 and CD8 TNFalpha(+) T cells specifically respond to FIV antigens. These responses were found to reach a peak at 9 weeks post-infection. It was further shown that the TNFalpha(+)CD8(+) responding T cells were contained within a CD8beta(low)CD62L(-) T cell subpopulation, expanded in FIV-infected cats. This T cell subpopulation which present features of activated CD8 T cells was further shown to be susceptible to spontaneous apoptosis following a short-term in vitro culture. Moreover, it was observed that cell death by apoptosis of this T cell subset was increased following FIV antigen-recognition. Therefore, FIV might alter immune homeostasis in inducing chronic activation of TNFalpha(+)CD8(+) T cells which eventually will die following antigen contact while deleting CD4(+) T cells. Interestingly, this study confirmed the strong similarity between FIV and HIV pathogenesis.

The purpose of this study has been to evaluate the immunohistochemical characteristics of human pterygial tissues in order to ascertain the possible contribution of an immunological mechanism in the pathogenesis of pterygium and to investigate the presence in the pterygial tissues of some melanoma-associated antigens, in order to evaluate if there may be a small possibility of correlation of the two diseases. Human biopsy specimens of pterygium were obtained by surgery for pterygium excision. Tissue segments were fixed and processed for paraffin embedding. Microtome sections were treated for the immunohistochemical demonstration of IgA, IgM, IgG, CD3, CD20, CD68, HLA-DR, Protein S100, HMB45, and Melan A using the avidin-biotin peroxidase method or the streptavidin biotin-alkaline phosphatase method. The findings suggest that all the effector components of the mucosal immune system are present in the human pterygium and, among the most sensitive markers for melanoma, only S100 shows immunoreactivity. An immunopathogenetic mechanism seems to be responsible for the pathogenesis of pterygium, perhaps being caused by pre-existing conjunctivitis or microtrauma in combination with the patient's predisposition. No correlation between pterygium and melanoma was found.

Intraoperative femoral fractures are a serious complication of total hip replacement. The purpose of this study was to evaluate the risk factors of intraoperative femoral fractures in a retrospective analysis of a series of 3,566 total hip replacements.The patients were divided into two groups, A and B. Group A patients had no intraoperative femoral fractures and Group B patients had intraoperative femoral fractures. In Group A there were 3,483 patients (97.7%) and in Group B, 83 (2.3%). The following potential risk factors were evaluated: sex, age, diagnosis, previous surgery at the homolateral hip, surgical approach, fixation type of the femoral component, prosthesis type, surgical stage during which the fracture occurred, and the lead operating surgeon.The fracture incidence was higher in females (p0.005) in uncemented femoral components (p = 0.005), in patients who had previous surgery at the homolateral hip (p0.005), and in revision surgery (p0.005).The analysis of intraoperative femoral fracture risk factors should allow the surgeon to improve the surgical performance and therefore reduce the incidence of this severe intraoperative complication.

SUMMARY Increasing evidence has demonstrated that the immune system closely interacts with other physiological systems, whose communications are mediated by circulating cytokines and hormones. The aim of our study was to test whether the number and cytolytic activity of NK cells in a group of relatively healthy Italian nonagenarians and centenarians were affected by the modifications of endocrine, metabolic and functional parameters that occur during ageing. Because of the extreme age of the study population, a cross-sectional analysis was performed. This study revealed that the group of oldest subjects with the highest number of NK cells and the best preserved cytolytic function also presented a preserved metabolism of thyroid hormones and vitamin D and integrity of muscle mass. In fact, the NK cell number and/or cytolytic activity of healthy subjects > 90 years old was positively associated with serum levels of vitamin D, while T3, FT4, i-PTH hormones and lean body mass were associated only with NK cell number. In conclusion, our results stress the paramount importance of nutritional evaluation in the clinical assessment of elderly people.

An ELMy H-mode 'snowflake' (SF) divertor is established and studied for the first time in the TCV tokamak. The H-mode access and the edge localized mode (ELM) dynamics are compared with a conventional single-null diverted configuration. The SF configuration exhibits 15% higher confinement and 2-3 times lower ELM frequency. Ideal MHD stability analysis suggests enhanced stability of the SF H-mode pedestal to mid- to high-toroidal-mode-number modes. The capability of the SF to redistribute the edge power on the additional strike points has been confirmed experimentally.

A new mechanism has recently been proposed that generates a radial flux of parallel momentum in toroidal plasmas. Namely, by considering up-down asymmetric flux surfaces, the symmetry following the magnetic field can be broken and an additional contribution to the turbulent momentum flux arises, potentially changing the intrinsic rotation profile. These predictions are tested with specific experiments on TCV. The intrinsic toroidal rotation is observed to change by roughly a factor of two when changing the up-down asymmetry of the plasma. More precisely, the toroidal rotation gradient changes in the outer part of the plasma, where the flux surface asymmetry is the highest. The experiments were performed for all combinations of the toroidal magnetic field and plasma current directions, that affect the sign of the predicted up-down asymmetry flux. In each case the variation of the intrinsic rotation profile with the up-down asymmetry is observed in the direction predicted by the theory.