Correlations of Gene Expression with Blood Lead Levels in Children with Autism Compared to Typically Developing Controls

The objective of this study was to examine the correlation between gene expression and lead (Pb) levels in blood in children with autism (AU, n = 37) compared to typically developing controls (TD, n = 15). We postulated that, though lead levels did not differ between the groups, AU children might metabolize lead differently compared to TD children. RNA was isolated from blood and processed on Affymetrix microarrays. Separate analyses of covariance (ANCOVA) corrected for age and gender were performed for TD, AU, and all subjects (AU + TD). To reduce false positives, only genes that overlapped these three ANCOVAs were considered. Thus, 48 probe sets correlated with lead levels in both AU and TD subjects and were significantly different between the groups (p(Diagnosis × log2 Pb) < 0.05). These genes were related mainly to immune and inflammatory processes, including MHC Class II family members and CD74. A large number (n = 791) of probe sets correlated (P ≤ 0.05) with lead levels in TD but not in AU subjects; and many probe sets (n = 162) correlated (P ≤ 0.05) with lead levels in AU but not in TD subjects. Only 30 probe sets correlated (P ≤ 0.05) with lead levels in a similar manner in the AU and TD groups. These data show that AU and TD children display different associations between transcript levels and low levels of lead. We postulate that this may relate to the underlying genetic differences between the two groups, though other explanations cannot be excluded

Magma plumbing systems: a geophysical perspective

Over the last few decades, significant advances in using geophysical techniques to image the structure of magma plumbing systems have enabled the identification of zones of melt accumulation, crystal mush development, and magma migration. Combining advanced geophysical observations with petrological and geochemical data has arguably revolutionised our understanding of, and afforded exciting new insights into, the development of entire magma plumbing systems. However, divisions between the scales and physical settings over which these geophysical, petrological, and geochemical methods are applied still remain. To characterise some of these differences and promote the benefits of further integration between these methodologies, we provide a review of geophysical techniques and discuss how they can be utilised to provide a structural context for and place physical limits on the chemical evolution of magma plumbing systems. For example, we examine how Interferometric Synthetic Aperture Radar (InSAR), coupled with Global Positioning System (GPS) and Global Navigation Satellite System (GNSS) data, and seismicity may be used to track magma migration in near real-time. We also discuss how seismic imaging, gravimetry and electromagnetic data can identify contemporary melt zones, magma reservoirs and/or crystal mushes. These techniques complement seismic reflection data and rock magnetic analyses that delimit the structure and emplacement of ancient magma plumbing systems. For each of these techniques, with the addition of full-waveform inversion (FWI), the use of Unmanned Aerial Vehicles (UAVs) and the integration of geophysics with numerical modelling, we discuss potential future directions. We show that approaching problems concerning magma plumbing systems from an integrated petrological, geochemical, and geophysical perspective will undoubtedly yield important scientific advances, providing exciting future opportunities for the volcanological community

Evaluation of prognostic risk models for postoperative pulmonary complications in adult patients undergoing major abdominal surgery: a systematic review and international external validation cohort study

Background Stratifying risk of postoperative pulmonary complications after major abdominal surgery allows clinicians to modify risk through targeted interventions and enhanced monitoring. In this study, we aimed to identify and validate prognostic models against a new consensus definition of postoperative pulmonary complications. Methods We did a systematic review and international external validation cohort study. The systematic review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE and Embase on March 1, 2020, for articles published in English that reported on risk prediction models for postoperative pulmonary complications following abdominal surgery. External validation of existing models was done within a prospective international cohort study of adult patients (≥18 years) undergoing major abdominal surgery. Data were collected between Jan 1, 2019, and April 30, 2019, in the UK, Ireland, and Australia. Discriminative ability and prognostic accuracy summary statistics were compared between models for the 30-day postoperative pulmonary complication rate as defined by the Standardised Endpoints in Perioperative Medicine Core Outcome Measures in Perioperative and Anaesthetic Care (StEP-COMPAC). Model performance was compared using the area under the receiver operating characteristic curve (AUROCC). Findings In total, we identified 2903 records from our literature search; of which, 2514 (86·6%) unique records were screened, 121 (4·8%) of 2514 full texts were assessed for eligibility, and 29 unique prognostic models were identified. Nine (31·0%) of 29 models had score development reported only, 19 (65·5%) had undergone internal validation, and only four (13·8%) had been externally validated. Data to validate six eligible models were collected in the international external validation cohort study. Data from 11 591 patients were available, with an overall postoperative pulmonary complication rate of 7·8% (n=903). None of the six models showed good discrimination (defined as AUROCC ≥0·70) for identifying postoperative pulmonary complications, with the Assess Respiratory Risk in Surgical Patients in Catalonia score showing the best discrimination (AUROCC 0·700 [95% CI 0·683–0·717]). Interpretation In the pre-COVID-19 pandemic data, variability in the risk of pulmonary complications (StEP-COMPAC definition) following major abdominal surgery was poorly described by existing prognostication tools. To improve surgical safety during the COVID-19 pandemic recovery and beyond, novel risk stratification tools are required. Funding British Journal of Surgery Society