Multichannel Time Synchronization Based on PTP through a High Voltage Isolation Buffer Network Interface for Thick-GEM Detectors

Data logging and complex algorithm implementations acting on multichannel systems with independent devices require the use of time synchronization. In the case of Gas Electron Multipliers (GEM) and Thick-GEM (THGEM) detectors, the biasing potential can be generated at the detector level via DC to DC converters operating at floating voltage. In this case, high voltage isolation buffers may be used to allow communication between the different channels. However, their use add non-negligible delays in the transmission channel, complicating the synchronization. Implementation of a simplified precise time protocol is presented for handling the synchronization on the Field Programmable Gate Array (FPGA) side of a Xilinx SoC Zynq ZC7Z030. The synchronization is done through a high voltage isolated bidirectional network interface built on a custom board attached to a commercial CIAA_ACC carrier. The results of the synchronization are shown through oscilloscope captures measuring the time drift over long periods of time, achieving synchronization in the order of nanoseconds

Borehole image techniques applied to identification of chert and dolomite layers in lacustrine sediments

Geophysical logging tools, particularly ultrasonic acoustic borehole image techniques, are applied on two different wells (CP1 and CP2) to identify and characterize the lacustrine interval (40m) of the Camp dels Ninots maardiatreme infill (Pliocene, Catalan Coastal Ranges). The CP1 well was cored and also geophysical logs and oriented borehole images were acquired. CP2 hole was partially cored but logging (geophysics and borehole images) was fully undertaken. Continuous core recovery in CP1 is compared with oriented images and is further used to identify and characterize highly reflective signals in a section of CP2 borehole that was not cored. These signals are related to silicified zones and belong to discontinuous centimetric chert nodules, while indurated massive carbonates are characterized as intervals of continuous reflectance. Despite opal nodules (chert) can be relatively small, they have a distinctive response in the ultrasonic borehole images.Peer Reviewe

Pilot study to introduce a notification card for partner notification of sexually transmitted infections in Catalonia, Spain, June 2010 to June 2011

We conducted a cross-sectional study in 10 primary care centres in Catalonia, to determine applicability, acceptability and effectiveness of partner notification cards used by patients diagnosed of a sexually transmitted infection (STI) and to characterise these and their sexual partners. Statutorily notifiable STIs included Chlamydia infection, gonorrhoea, syphilis, human immunodeficiency virus (HIV) infection or other STIs as deemed necessary by the treating physician. Between June 2010 and June 2011, 219 index cases were enrolled, of whom 130 were men (59.4%), 71 of them men who have sex with men (54.6%). Chlamydia infection (41.1%), gonorrhoea (17.8%) and syphilis (16.0%) were the STIs most frequently diagnosed. HIV infection accounted for 4% of cases. A total of 687 sexual partners were reported, and 300 of these were traceable through the notification card (45.7%). Those who did not report traceable contacts were older (mean age: 34 years versus 31 years, p=0.03). The main reason for not distributing the card was anonymous sexual intercourse (38%). Patient referral notification cards can reach a high percentage of sexual partners at risk. However, only few notified sexual partners attended participating health centres. Internet-based partner notification may be considered in order to reach those partners not otherwise traceable

Objectively Measured Physical Activity Reduces the Risk of Mortality among Brazilian Older Adults.

OBJECTIVES: Use of objectively measured physical activity (PA) in older adults to assess relationship between PA and risk of all-causes mortality is scarce. This study evaluated the associations of PA based on accelerometry and a questionnaire with the risk of mortality among older adults from a city in Southern Brazil. DESIGN: A cohort study. SETTING: Urban area of Pelotas, Southern Brazil. PARTICIPANTS: A representative sample of older adults (≥60 y) from Pelotas, enrolled in 2014. MEASUREMENTS: Overall physical activity (mg), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were estimated by raw accelerometer data. The International Physical Activity Questionnaire estimated leisure time and commuting PA. Hazard ratios (excluding deaths in the first 6 mo) stratified by sex were estimated by Cox regression analysis considering adjustment for confounders. RESULTS: From the 1451 older adults interviewed in 2014, 145 died (10%) after a follow-up of an average 2.6 years. Men and women in the highest tertile of overall PA had on average a 77% and 92% lower risk of mortality than their less active counterparts (95% confidence interval [CI] = .06-.84 and 95% CI = .01-.65, respectively). The highest tertile of LPA was also related to a lower risk of mortality in individuals of both sexes (74% and 91% lower risk among men and women, respectively). MVPA statistically reduced the risk of mortality only among women (hazard ratio [HR] = .30 and HR = .07 in the second and third tertiles). Self-reported leisure-time PA was statistically associated with a lower risk of mortality only among men. Women in the highest tertiles of commuting PA showed a lower risk of mortality than those in the reference group. CONCLUSION: Accelerometry-based PA was associated with a lower risk of mortality among Brazilian older adults. Older individuals should practice any type of PA. J Am Geriatr Soc 68:137-146, 2019

Objectively Measured Physical Activity Reduces the Risk of Mortality among Brazilian Older Adults.

OBJECTIVES: Use of objectively measured physical activity (PA) in older adults to assess relationship between PA and risk of all-causes mortality is scarce. This study evaluated the associations of PA based on accelerometry and a questionnaire with the risk of mortality among older adults from a city in Southern Brazil. DESIGN: A cohort study. SETTING: Urban area of Pelotas, Southern Brazil. PARTICIPANTS: A representative sample of older adults (≥60 y) from Pelotas, enrolled in 2014. MEASUREMENTS: Overall physical activity (mg), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were estimated by raw accelerometer data. The International Physical Activity Questionnaire estimated leisure time and commuting PA. Hazard ratios (excluding deaths in the first 6 mo) stratified by sex were estimated by Cox regression analysis considering adjustment for confounders. RESULTS: From the 1451 older adults interviewed in 2014, 145 died (10%) after a follow-up of an average 2.6 years. Men and women in the highest tertile of overall PA had on average a 77% and 92% lower risk of mortality than their less active counterparts (95% confidence interval [CI] = .06-.84 and 95% CI = .01-.65, respectively). The highest tertile of LPA was also related to a lower risk of mortality in individuals of both sexes (74% and 91% lower risk among men and women, respectively). MVPA statistically reduced the risk of mortality only among women (hazard ratio [HR] = .30 and HR = .07 in the second and third tertiles). Self-reported leisure-time PA was statistically associated with a lower risk of mortality only among men. Women in the highest tertiles of commuting PA showed a lower risk of mortality than those in the reference group. CONCLUSION: Accelerometry-based PA was associated with a lower risk of mortality among Brazilian older adults. Older individuals should practice any type of PA. J Am Geriatr Soc 68:137-146, 2019

Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles

Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region – either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.This work was supported by RETICC RD06/0020/0035, RD06/0020/0059 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER), AES PI16/000476 (Instituto de Salud Carlos III, Madrid, Spain and FONDOS FEDER), GRS909A14 (JCYL) and CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER)

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.Acknowledgements: This work was supported by Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (to MLM-C), Ministerio de Ciencia e Innovación CONSOLIDER-INGENIO 2010 Program Grant CSD2008-00005 (to LAMC); Spanish Ministry of Economy and Competitiveness Grant BFU2013-47531-R, BFU2016-77408-R, PID2019-109055RB-100 (to L.A.M.-C.) (MINECO/FEDER, UE); Asociación Española contra el Cáncer (MLM-C, TC-D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.), La Caixa Foundation Program (to M.L.M.-C.), Fundacion BBVA UMBRELLA project (to M.L.M.-C.), Ayuda RYC2020-029316-I financiada por MICIN/AEI/10.13039/501100011033 (to TC-D), Plataforma de Investigación Clínica-SCReN (PT17 0017 0020) (to M.I.-L.), programa retos RTC2019-007125-1 (to M.L.M.-C, J.S.), Proyectos Investigacion en Salud DTS20/00138 (to M.L.M.-C., J.S), ERA-Net E-Rare EJP RD Joint Translational Call for Rare Diseases FIGHT-CNNM2 (EJPRD19-040) and from Instituto Carlos III, Spain (REF G95229142) (to L.A.M.-C.), US National Institutes of Health under grant CA217817 (to D.B.), Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thankMINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644) and PhD fellowship fromMINECO (REF BES-2017-080435) awarded to I.G.-R. The collection and storage of patients tissues was supported by the Newcastle Biomedicine Biobank and the European Community’s Seventh Framework Programme (FP7/2001–2013) and Cancer Research UK awards Cancer Research UK grants C18342/A23390; C9380/A18084 and C9380/A26813. Finally, we would like to acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others