Demonstration: Economic Analysis and Expert Testimony—Plaintiff\u27s Conference

This article is a demonstration on the use of economic experts. The demonstration is based loosely on Mobil’s attempted take-over of Marathon Oil Company. However, the oil companies involved here are named Major, which is the second largest oil company in the United States, and Olympic, which is the largest supplier to independents. Any resemblance of Major and Olympic to any other firm, entity or person, living or not, is purely coincidental. The demonstration is divided into two parts. The first part is the conference. A conference of plaintiff’s team will be followed by a conference of defendant’s team

Demonstration: Economic Analysis and Expert Testimony—Plaintiff\u27s Conference

This article is a demonstration on the use of economic experts. The demonstration is based loosely on Mobil’s attempted take-over of Marathon Oil Company. However, the oil companies involved here are named Major, which is the second largest oil company in the United States, and Olympic, which is the largest supplier to independents. Any resemblance of Major and Olympic to any other firm, entity or person, living or not, is purely coincidental. The demonstration is divided into two parts. The first part is the conference. A conference of plaintiff’s team will be followed by a conference of defendant’s team

Microbial genomics amidst the Arctic crisis

The Arctic is warming – fast. Microbes in the Arctic play pivotal roles in feedbacks that magnify the impacts of Arctic change. Understanding the genome evolution, diversity and dynamics of Arctic microbes can provide insights relevant for both fundamental microbiology and interdisciplinary Arctic science. Within this synthesis, we highlight four key areas where genomic insights to the microbial dimensions of Arctic change are urgently required: the changing Arctic Ocean, greenhouse gas release from the thawing permafrost, 'biological darkening' of glacial surfaces, and human activities within the Arctic. Furthermore, we identify four principal challenges that provide opportunities for timely innovation in Arctic microbial genomics. These range from insufficient genomic data to develop unifying concepts or model organisms for Arctic microbiology to challenges in gaining authentic insights to the structure and function of low-biomass microbiota and integration of data on the causes and consequences of microbial feedbacks across scales. We contend that our insights to date on the genomics of Arctic microbes are limited in these key areas, and we identify priorities and new ways of working to help ensure microbial genomics is in the vanguard of the scientific response to the Arctic crisis

The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers

BACKGROUND: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection. METHODS: A prospective observational study of HCW's in Scotland (UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general local population, were studied for comparison. New infections (up to 2/12/2020) post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection. RESULTS: A total of 2063 health and social care workers were recruited for this study. At enrolment 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85–6.16, p<0.0001). Dentists were most likely to test positive. 97.3% of patients who had previously tested positive for SARS-CoV-2 by RT-PCR had positive antibodies. 18.7% had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCW who were previously antibody negative and one symptomatic RT-PCR positive re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (HR 0.15, 95% CI 0.06 to 0.35, p=0.026). CONCLUSION: HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all infected individuals developed an antibody response which was 85% effective in protecting against re-infection with SARS-CoV-2

Beyond counting climate consensus

Several studies have been using quantified consensus within climate science as an argument to foster climate policy. Recent efforts to communicate such scientific consensus attained a high public profile but it is doubtful if they can be regarded successful. We argue that repeated efforts to shore up the scientific consensus on minimalist claims such as ‘humans cause global warming’ are distractions from more urgent matters of knowledge, values, policy framing and public engagement.  Such efforts to force policy progress through communicating scientific consensus misunderstand the relationship between scientific knowledge, publics and policymakers. More important is to focus on genuinely controversial issues within climate policy debates where expertise might play a facilitating role. Mobilising expertise in policy debates calls for judgment, context and attention to diversity, rather than deferring to formal quantifications of narrowly scientific claims

Validation of an open source, remote web‐based eye‐tracking method (WebGazer) for research in early childhood

Measuring eye movements remotely via the participant's webcam promises to be an attractive methodological addition to in-person eye-tracking in the lab. However, there is a lack of systematic research comparing remote web-based eye-tracking with in-lab eye-tracking in young children. We report a multi-lab study that compared these two measures in an anticipatory looking task with toddlers using WebGazer.js and jsPsych. Results of our remotely tested sample of 18-27-month-old toddlers (N = 125) revealed that web-based eye-tracking successfully captured goal-based action predictions, although the proportion of the goal-directed anticipatory looking was lower compared to the in-lab sample (N = 70). As expected, attrition rate was substantially higher in the web-based (42%) than the in-lab sample (10%). Excluding trials based on visual inspection of the match of time-locked gaze coordinates and the participant's webcam video overlayed on the stimuli was an important preprocessing step to reduce noise in the data. We discuss the use of this remote web-based method in comparison with other current methodological innovations. Our study demonstrates that remote web-based eye-tracking can be a useful tool for testing toddlers, facilitating recruitment of larger and more diverse samples; a caveat to consider is the larger drop-out rate

Dried blood spots as a source of anti-malarial antibodies for epidemiological studies

BACKGROUND: Blood spots collected onto filter paper are an established and convenient source of antibodies for serological diagnosis and epidemiological surveys. Although recommendations for the storage and analysis of small molecule analytes in blood spots exist, there are no published systematic studies of the stability of antibodies under different storage conditions. METHODS: Blood spots, on filter paper or glass fibre mats and containing malaria-endemic plasma, were desiccated and stored at various temperatures for different times. Eluates of these spots were assayed for antibodies against two Plasmodium falciparum antigens, MSP-119 and MSP2, and calculated titres used to fit an exponential (first order kinetic) decay model. The first order rate constants (k) for each spot storage temperature were used to fit an Arrhenius equation, in order to estimate the thermal and temporal stability of antibodies in dried blood spots. The utility of blood spots for serological assays was confirmed by comparing antibodies eluted from blood spots with the equivalent plasma values in a series of samples from North Eastern Tanzania and by using blood spot-derived antibodies to estimate malaria transmission intensity in this site and for two localities in Uganda. RESULTS: Antibodies in spots on filter paper and glass fibre paper had similar stabilities but blood was more easily absorbed onto filter papers than glass fibre, spots were more regular and spot size was more closely correlated with blood volume for filter paper spots. Desiccated spots could be stored at or below 4 degrees C for extended periods, but were stable for only very limited periods at ambient temperature. When desiccated, recoveries of antibodies that are predominantly of IgG1 or IgG3 subclasses were similar. Recoveries of antibodies from paired samples of serum and of blood spots from Tanzania which had been suitably stored showed similar recoveries of antibodies, but spots which had been stored for extended periods at ambient humidity and temperature showed severe loss of recoveries. Estimates of malaria transmission intensity obtained from serum and from blood spots were similar, and values obtained using blood spots agreed well with entomologically determined values. CONCLUSION: This study has demonstrated the suitability of filter paper blood spots paper for collection of serum antibodies, and provided clear guidelines for the treatment and storage of filter papers which emphasize the importance of desiccation and minimisation of time spent at ambient temperatures. A recommended protocol for collecting, storing and assaying blood spots is provided

Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders

Germline pathogenic variants in two genes encoding the lysine-specific histone methyltransferase genes SETD1A and SETD2 are associated with neurodevelopmental disorders (NDDs) characterised by developmental delay and congenital anomalies. The SETD1A and SETD2 gene products play a critical role in chromatin-mediated regulation of gene expression. Specific methylation episignatures have been detected for a range of chromatin gene-related NDDs and have impacted clinical practice by improving interpretation of variant pathogenicity. To investigate if SETD1A and/or SETD2-related NDDs are associated with a detectable episignature, we undertook targeted genome-wide methylation profiling of > 2 M CpGs using a next generation sequencing based assay. Comparison of methylation profiles in patients with SETD1A variants (n = 6) did not reveal evidence of a strong methylation episignature. Review of the clinical and genetic features of SETD2 patient group revealed that, as reported previously, there were phenotypic differences between patients with truncating mutations (n = 4, Luscan-Lumish syndrome; MIM:616831) and those with missense codon 1740 variants (p.Arg1740Trp (n = 4) and p.Arg1740Gln (n = 2)). Both SETD2 subgroups demonstrated a methylation episignature which was characterised by hypomethylation and hypermethylation events respectively. Within the codon 1740 subgroup, both the methylation changes and clinical phenotype were more severe in those with p.Arg1740Trp variants. We also noted that two of 10 cases with a SETD2-NDD had developed a neoplasm. These findings reveal novel epigenotype-genotype–phenotype correlations in SETD2-NDDs and predict a gain-of-function mechanism for SETD2 codon 1740 pathogenic variants

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate