Applying robotics to HAZMAT

The use of robotics in situations involving hazardous materials can significantly reduce the risk of human injuries. The Emergency Response Robotics Project, which began in October 1990 at the Jet Propulsion Laboratory, is developing a teleoperated mobile robot allowing HAZMAT (hazardous materials) teams to remotely respond to incidents involving hazardous materials. The current robot, called HAZBOT III, can assist in locating characterizing, identifying, and mitigating hazardous material incidents without risking entry team personnel. The active involvement of the JPL Fire Department HAZMAT team has been vital in developing a robotic system which enables them to perform remote reconnaissance of a HAZMAT incident site. This paper provides a brief review of the history of the project, discusses the current system in detail, and presents other areas in which robotics can be applied removing people from hazardous environments/operations

The British Army, information management and the First World War revolution in military affairs

Information Management (IM) – the systematic ordering, processing and channelling of information within organisations – forms a critical component of modern military command and control systems. As a subject of scholarly enquiry, however, the history of military IM has been relatively poorly served. Employing new and under-utilised archival sources, this article takes the British Expeditionary Force (BEF) of the First World War as its case study and assesses the extent to which its IM system contributed to the emergence of the modern battlefield in 1918. It argues that the demands of fighting a modern war resulted in a general, but not universal, improvement in the BEF’s IM techniques, which in turn laid the groundwork, albeit in embryonic form, for the IM systems of modern armies. KEY WORDS: British Army, Information Management, First World War, Revolution in Military Affairs, Adaptatio

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Effective use of cerium anomalies as a redox proxy in carbonate-dominated marine settings

Rare earth elements and yttrium (REY) have a distinct distribution pattern in seawater, and this pattern may be faithfully preserved in carbonate sediments and rocks. Anomalous concentrations of redox-sensitive cerium (Ce) compared with neighbouring REY originate in oxic water column conditions, and as such, Ce anomalies can provide a potentially useful redox proxy in carbonate-dominated marine settings. The methods used to extract REY from carbonates vary widely, and may suffer from widespread leaching of REY from accessory non-carbonate minerals and organic matter, limiting the application of Ce anomalies for palaeo-redox reconstruction. We have systematically compared different methods on 195 carbonate samples with varying purity (% carbonate) from both modern and ancient environments. We used sequential leaching experiments in nitric acid to identify the most ‘seawater-like’ portion of the carbonate sample where contributions from non-carbonate minerals and organic matter are minimised. We also compared the results of sample dissolution in different types and strengths of acid. Our results confirm that REY concentrations can be inadvertently contaminated by partial leaching of clays and Fe (oxyhydr)oxides during a single-step digestion, and we suggest a pre-leach of 20% of the sample, followed by a partial leach of 40% of the sample to selectively dissolve carbonate. We suggest that REY studies are optimised in carbonates with > 85% CaCO₃, and show that dolomites behave differently during the leaching process and must be treated separately. We present REY patterns for modern carbonate-rich sediments from a range of environments, and show that seawater REY are faithfully preserved in some non-skeletal carbonate, but modified leaching procedures are necessary for impure, unlithified or organic rich carbonate sediments. We combine REY with Fe-speciation data to identify how Fe oxides and clays contribute to the REY signal and explore how the two proxies can be used together to provide a complex and high-resolution redox reconstruction in carbonate-dominated marine environments

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

Considerations for the safe prescribing and use of COX-2-specific inhibitors

The majority of the "Australian COX-2-Specific Inhibitor (CSI) Prescribing Group" endorse the following points: CSIs are equivalent to non-steroidal anti-inflammatory drugs (NSAIDs) as anti-inflammatory agents. CSIs and NSAIDs modify symptoms but do not after the course of musculoskeletal disease. CSIs do not eliminate the occurrence of ulcers or their serious complications, but are associated with considerably fewer peptic ulcers, slightly fewer upper GI symptoms and, according to published reports, fewer serious upper GI complications, notably bleeding, than NSAIDs. CSIs and NSAIDs have similar effects on renal function and blood pressure. Whether any CSI poses a risk to cardiovascular safety remains subject to debate. Comorbidities and coprescribed drugs must be considered before initiating CSI (or NSAID) therapy. Patients prescribed CSIs (or NSAIDs) should be reviewed within the first few weeks of therapy to assess effectiveness, identify adverse effects and determine the need for ongoing therapy

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

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

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

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.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 (VAFPeer reviewe