Realtime gas emission monitoring at hazardous sites using a distributed point-source sensing infrastructure

This paper describes a distributed point-source monitoring platform for gas level and leakage detection in hazardous environments. The platform, based on a wireless sensor network (WSN) architecture, is organised into sub-networks to be positioned in the plant’s critical areas; each sub-net includes a gateway unit wirelessly connected to the WSN nodes, hence providing an easily deployable, stand-alone infrastructure featuring a high degree of scalability and reconfigurability. Furthermore, the system provides automated calibration routines which can be accomplished by non-specialized maintenance operators without system reliability reduction issues. Internet connectivity is provided via TCP/IP over GPRS (Internet standard protocols over mobile networks) gateways at a one-minute sampling rate. Environmental and process data are forwarded to a remote server and made available to authenticated users through a user interface that provides data rendering in various formats and multi-sensor data fusion. The platform is able to provide real-time plant management with an effective; accurate tool for immediate warning in case of critical events

Transcriptomics age acceleration in prolonged treated HIV infection

Biological aging in people with HIV (PWH) with prolonged successful antiretroviral therapy (ART) is convoluted and poorly defined. Here, we aimed to investigate the transcriptomics age estimator (TAE) in a cohort of 178 PWH on prolonged successful ART with immune reconstitution and viral suppression from the Copenhagen Comorbidity (COCOMO) cohort. We also used 143 clinical, demographical, and lifestyle factors to identify the confounders potentially responsible or associated with age acceleration. Among the PWH, 43% had an accelerated aging process (AAP), and 21% had decelerated aging process (DAP). DAP is linked with older age, European ancestry, and higher use of tenofovir disoproxil/alafenamide fumarate. A directionally class-based gene set enrichment analysis identified the upregulation of inflammatory pathways (e.g., cytokine and Retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways) and immune response like T-cell receptor signaling, antigen processing, and presentation in AAP and the downregulation of metabolic processes like oxidative phosphorylation, pyruvate metabolism

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic 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

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic 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

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Maxillary segmental micro osteotomy: a human cadaver study on the efficacy of the technique

Purpose: Ultrasonic bone cutting was recently introduced as a feasible alternative to the conventional tools of cranio-maxillofacial surgery because it offers improved precision and safety. This study examined the feasibility of minimally invasive orthodontic or preprosthetic surgery using a piezosurgery device for lateroposterior maxillary segmental osteotomy. Materials and Methods: Four fresh cadaveric heads were obtained for this study. Maxillary posterior osteotomy was performed using piezoelectric surgery. To preserve the vascular supply, only 1 vestibular incision was made during surgery. The Mectron Piezosurgery1 unit is a multipurpose device that uses micrometric ultrasonic piezoelectric vibrations with a variable frequency and cutting energy. The strategy for maxillary osteotomy included 1 horizontal osteotomy, 2 vertical osteotomies, and 1 palatal osteotomy performed transantrally without incision of the mucoperiosteum. The osteotomies were performed using a piezodevice (OT7-type inserts: 0.55 and 0.35mm). In total, 1 horizontal cut (3mmabove the roots of the teeth), 2 vertical bone cuts, and 1 palatal osteotomy were made without incision of the palatal mucoperiosteum. Gentle dissection of the buccal fat pad was used to promote the healing of hard and soft tissues in the osteotomized zone. Results: No damage to soft tissues, including the palatal mucosa, occurred. The buccal fat pad was mobilized easily without requiring an additional incision. The osteotomic sites were linear and clean in the palatal aspect. The integrity of the vascular network was maintained because of the lack of damage to the palatal mucosa. No chisels were used during the osteotomies. Discussion: This cadaveric study shows the feasibility of using piezosurgery for segmental maxillary osteotomy. This report outlines a new and simple application of segmental maxillary micro-osteotom

Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

Abstract Background Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cells homeostatic polyclonal proliferation and regulates Th17/regulatory T-cell balance, immunological functions known to be affected during primary HIV infection. The aim of this study was to describe immune recovery in primary and chronic HIV infection and possible impact of TSLP. Methods Prospective study including 100 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 42), late presenters without advanced disease (200–350 CD4+ T cells/μL, N = 24) and with advanced disease (<200 CD4+ T cells/μL, N = 20) and). Immune recovery was defined as increase in CD4+ T cells count from baseline to a given time of follow-up. Plasma TSLP was determined using ELISA and CD4+ T cell subpopulations (recent thymic emigrants, naïve and memory cells) were measured using flow cytometry at baseline and after 6, 12 and 24 months of cART. Results Immune recovery was comparable in all groups, and no differences in immune homeostasis were found between primary HIV infection and early presenters, whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters. TSLP was elevated in primary HIV infection at baseline and after 24 months of cART. Interestingly, TSLP was negatively associated with proportion of recent thymic emigrants (correlation coefficient −0.60, p = 0.030). TSLP was not associated with immune recovery in primary HIV infection. Conclusions Immune recovery was comparable in primary and chronic HIV infection whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters supporting early initiation of cART. Higher plasma TSLP was found in primary HIV infection, and TSLP was associated with lower thymic output, but not with immune recovery. These findings indicate a possible role of TSLP in immune homeostasis in HIV infection but do not support TSLP to affect immune recovery in primary HIV infection

Tryptophan catabolism and immune activation in primary and chronic HIV infection

Abstract Background Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation. Methods Prospective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (<200 CD4+ T cells/μL, N = 19)). Kynurenine and tryptophan were analysed by liquid chromatography–tandem mass spectrometry. Total CD4+ and CD8+ T cells were determined and proportion of activated CD38 + HLA-DR+ Tcells was measured using flow cytometry at baseline and after 6 and 12 months of cART. Results At baseline, primary HIV infection had higher KTR than early presenters. However, similar KTR in primary HIV infection and early presenters was found after cART initiation, while late presenters had higher KTR at all time points. In primary HIV infection and early presenters, KTR was positively associated with proportion of activated cells at baseline. Furthermore, in early presenters the KTR at baseline was associated with proportion of activated cells after 6 and 12 months. Interestingly, in primary HIV infection the KTR at baseline was positively associated with reduction in proportion of CD8 + CD38 + HLA-DR T cells after 6 and 12 months. Conclusions Lower kynurenine/tryptophan ratio during follow-up was found after early initiation of cART. KTR in primary HIV infection and early presenters was positively associated with immune activation. Importantly, KTR in primary HIV infection predicted the magnitude of subsequent reduction in immune activation. Thus, a beneficial effect of early cART on KTR was suggested