Fuzzy Logic Method for the Speed Estimation in All-Wheel Drive Electric Racing Vehicles

This paper presents a method for the vehicle speed estimation with a Fuzzy Logic based algorithm. The algorithm acquires the measurements of the yaw rate, steering angle, wheel velocities and exploits a set of five Fuzzy Logics dedicated to different driving conditions. The technique estimates the speed exploiting a weighted average of the contributions provided by the longitudinal acceleration and the credibility assigned by the Fuzzy Logics to the measurements of the wheels' speed. The method is experimentally evaluated on an all-wheel drive electric racing vehicle and is valid for the front and rear wheel drive configurations. The experimental validation is performed by comparing the obtained estimation with the result of computing the speed as the average of the linear velocity of the four wheels. A comparison to the integral of the vehicle acceleration over time is reported

First report of the presence of Necrodes littoralis (L.) (Coleoptera: Silphidae) on a human corpse in Italy

The colonization of a human body by Necrodes littoralis (L.) (Coleoptera: Silphidae) is reported for the first time in Italy. This species is both necrophagous and predator of necrophagous fauna. The body colonized by the coleopteran was found indoors, in an advanced decomposition stage, in a suburban area of Cosenza (Calabria, Southern Italy) in November. Insects (adults, puparia and larvae) were collected on and around the body. Puparia and larvae were raised in the laboratory until the adult stage for morphological identification, which was carried out through taxonomical keys. Besides N. littoralis, also the presence of Calliphora vicina Robineau-Desvoidy, Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), Hydrotaea dentipes (Fabricius) (Diptera: Muscidae), and Creophilus maxillosus (L.) (Coleoptera: Staphylinidae) was detected. Necrodes littoralis is a species of forensic interest because it may colonize human and vertebrate corpses and has been reported elsewhere in Europe

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin. © 2010 Movement Disorder Society

The Use of Music and Brain Stimulation in Clinical Settings: Frontiers and Novel Approaches for Rehabilitation in Pathological Aging

Aging is a phase of life characterized by the increasing risk of occurring neurodegenerative pathologies, as well as stroke and physical decline. Patients in such clinical conditions are known to benefit from programs able to promote the improvement of associated cognitive, functional, and behavioral disorders. In recent times, growing empirical evidence showed the efficacy of active and passive music-based interventions to be the highest when used for healing these diseases. Additionally, very latest research found the combination of electrical neurostimulation with music to have potential utility for clinical older adult populations, as it may amplify the impulse to neuroplasticity and, by consequence, the rehabilitation gains. Reiterating of active music making induces changes in multiple brain regions bringing to the enhancement of cognitive and sensorimotor skills, while merely listening to pleasurable music stimulates dopaminergic regions of the brain improving cognition, motivation, and mood in a variety of neurological diseases. The versatility of music-based interventions in combination with new technologies allows an effective application of innovative therapeutic techniques. Moreover, their easy implementation in healthcare settings and their positive effects on both recovery and patients’ quality of life makes the integration of music-based interventions with conventional rehabilitation approaches highly desirable

The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.

Abstract Thyroid cancer is frequently associated with the oncogenic conversion of the RET receptor tyrosine kinase. RET gene rearrangements, which lead to the generation of chimeric RET/papillary thyroid carcinoma (PTC) oncogenes, occur in PTC, whereas RET point mutations occur in familial multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinomas (MTC). We showed previously that the expression of the receptor-type protein tyrosine phosphatase J (PTPRJ) is suppressed in neoplastically transformed follicular thyroid cells. We now report that PTPRJ coimmunoprecipitates with wild-type RET and with the MEN2A-associated RET(C634R) oncoprotein but not with the RET/PTC1 and RET-MEN2B isoforms. Using mutated forms of PTPRJ and RET-MEN2A, we show that the integrity of the respective catalytic domains is required for the PTPRJ/RET-MEN2A interaction. PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels. In line with this finding, adoptive PTPRJ expression reduced the oncogenic activity of RET(C634R) in an in vitro focus formation assay of NIH3T3 cells. As expected from the coimmunoprecipitation results, the RET(M918T) oncoprotein, which is associated to MEN2B and sporadic MTC, was resistant to the dephosphorylating activity of PTPRJ. Taken together, these findings identify RET as a novel substrate of PTPRJ and suggest that PTPRJ expression levels may affect tumor phenotype associated with RET/PTC1 and RET(C634R) mutants. On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation. (Cancer Res 2006; 66(12): 6280-7

Image-based sensing of salt stress in grapevine

Grapevine is among the most economically important crops suffering environmental constraints, including drought and salt stress. Although imaging is increasingly used to detect abiotic stress in agriculture, image-based phenotyping in grapevine still needs optimisation. This study presents the RGB-(red, green, blue)-based phenotyping of the early stage of salt stress response in potted grapevine (Aleatico/SO4) irrigated with saline water (100 mM NaCl) for 9 days in contrast with vines irrigated with fresh water. The response was measured using stomatal conductance (gs), net photosynthetic rate (A), transpiration (E), maximum potential photosynthetic efficiency (Fv/Fm), stem water potential (SWP) concurrently with RGB imaging via a robotised platform. The image-based phenotyping of salt-stressed vines employed two sets of measurements: (i) the pixel fraction of specific colour bands (Yellow, Green, Brown and Dark Green) and (ii) the mean pixel value of R, G and B and other RGB-based colorimetric indexes. Results show that the responses of gs, A, E, Fv/Fm were closely related to increasing soil electrical conductivity (EC) and that imaging could detect the EC threshold of approx. 4 dS m-1 causing a ~60 % decrease in these physiological traits compared to the pre-stress level. The SWP declined to about –0.7 MPa at the end of the experiment. The change of the relative pixel fraction of Dark Green to increasing EC has been analysed within a dose-response context, showing that a decrease of 1 % of the Dark Green colour band corresponded to the 4 dS m-1 EC threshold. This study also examined the use of the mean pixel value of the R, G and B channels as proxies of EC along with new RGB-based indexes resulting from the rearrangement of original R, G and B mean pixel values. Results show the suitability of the mean pixel value of R and Coloration Index [(R-B)/R] to serve as predictors of EC (R2 >= 0.80)

Testicular dysfunction in 47, XXY boys: when it all begins. A semi-longitudinal study

Objective: Klinefelter syndrome is the most common chromosomal disorder in males, and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal and quantitative ultrasound data in a life-course perspective. Design: Prospective semi-longitudinal study. Methods: We included 155 subjects with 47, XXY karyotype (age range: 7 months - 55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal and testicular ultrasound assessments were performed. Results: Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/FSH ratio thereafter. The Testosterone/LH ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level. Conclusions: The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients

Severity of Hepatocyte Damage and Prognosis in Cirrhotic Patients Correlate with Hepatocyte Magnesium Depletion

We aimed to evaluate the magnesium content in human cirrhotic liver and its correlation with serum AST levels, expression of hepatocellular injury, and MELDNa prognostic score. In liver biopsies obtained at liver transplantation, we measured the magnesium content in liver tissue in 27 cirrhotic patients (CIRs) and 16 deceased donors with healthy liver (CTRLs) by atomic absorption spectrometry and within hepatocytes of 15 CIRs using synchrotron-based X-ray fluorescence microscopy. In 31 CIRs and 10 CTRLs, we evaluated the immunohistochemical expression in hepatocytes of the transient receptor potential melastatin 7 (TRPM7), a magnesium influx chanzyme also involved in inflammation. CIRs showed a lower hepatic magnesium content (117.2 (IQR 110.5–132.9) vs. 162.8 (IQR 155.9–169.8)  g/g; p &lt; 0.001) and a higher percentage of TRPM7 positive hepatocytes (53.0 (IQR 36.8–62.0) vs. 20.7 (10.7–32.8)%; p &lt; 0.001) than CTRLs. In CIRs, MELDNa and serum AST at transplant correlated: (a) inversely with the magnesium content both in liver tissue and hepatocytes; and (b) directly with the percentage of hepatocytes stained intensely for TRPM7. The latter also directly correlated with the worsening of MELDNa at transplant compared to waitlisting. Magnesium depletion and overexpression of its influx chanzyme TRPM7 in hepatocytes are associated with severity of hepatocyte injury and prognosis in cirrhosis. These data represent the pathophysiological basis for a possible beneficial effect of magnesium supplementation in cirrhotic patients

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

BACKGROUND: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. METHODS/DESIGN: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. DISCUSSION: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873

Survival analysis of a multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC)

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