Lipid Metabolism and Comparative Genomics

Unilever asked the Study Group to focus on two problems. The first concerned dysregulated lipid metabolism which is a feature of many diseases including metabolic syndrome, obesity and coronary heart disease. The Study Group was asked to develop a model of the kinetics of lipoprotein metabolism between healthy and obese states incorporating the activities of key enzymes. The second concerned the use of comparative genomics in understanding and comparing metabolic networks in bacterium. Comparative genomics is a method to make inferences on the genome of a new organism using information of a previously charaterised organism. The first mathematical question is how one would quantify such a metabolic map in a statistical sense, in particular, where there are different levels of confidence for presense of different parts of the map. The next and most important question is how one can design a measurement strategy to maximise the confidence in the accuracy of the metabolic map

‘Pizza every day – why?’: A survey to evaluate the impact of COVID‐19 guidelines on secondary school food provision in the UK

The nutritional requirements of adolescence and the reported poor UK eating behaviours of young people are a significant public health concern. Schools are recognised as an effective ‘place’ setting to enable improvement to nutrition outcomes. The COVID‐19 pandemic resulted in UK school closures from March 2020. In re‐opening in September 2020, schools were required to meet guidelines to ensure the minimised impact of COVID‐19 on the population (DfE 2020). We aimed to evaluate the impact of COVID‐19 school guidelines on secondary and post‐16 (16–18 years) food provision. An online survey was posted on 8th October to 1st December 2020, targeted at young people, parents and staff of secondary/post‐16 education establishments in the UK. Two hundred and fifty‐two responses were received, of which 91% reported a change in their school food provision, 77% reported time for lunch was shortened and 44% indicated the provision was perceived as less healthy during September 2020 (post‐lockdown school return) compared with March 2020 (pre‐lockdown). Analyses demonstrated that time, limited choice and healthiness impacted negatively upon young people's school food experience. The COVID‐19 pandemic has presented a huge challenge to the delivery of healthy school food to young people. Therefore, schools require more support in following national food standards and incorporating nutrition education and behaviour change strategies within current guidelines

Ethics of personalized information filtering

Online search engines, social media, news sites and retailers are all investing heavily in the development of ever more refined information filtering to optimally tune their services to the specific demands of their individual users and customers. In this position paper we examine the privacy consequences of user profile models that are used to achieve this information personalization, the lack of transparency concerning the filtering choices and the ways in which personalized services impact the user experience. Based on these considerations we argue that the Internet research community has a responsibility to increase its efforts to investigate the means and consequences of personalized information filtering

Long-read metagenomics of soil communities reveals phylum-specific secondary metabolite dynamics

Microbial biosynthetic gene clusters (BGCs) encoding secondary metabolites are thought to impact a plethora of biologically mediated environmental processes, yet their discovery and functional characterization in natural microbiomes remains challenging. Here we describe deep long-read sequencing and assembly of metagenomes from biological soil crusts, a group of soil communities that are rich in BGCs. Taking advantage of the unusually long assemblies produced by this approach, we recovered nearly 3,000 BGCs for analysis, including 712 full-length BGCs. Functional exploration through metatranscriptome analysis of a 3-day wetting experiment uncovered phylum-specific BGC expression upon activation from dormancy, elucidating distinct roles and complex phylogenetic and temporal dynamics in wetting processes. For example, a pronounced increase in BGC transcription occurs at night primarily in cyanobacteria, implicating BGCs in nutrient scavenging roles and niche competition. Taken together, our results demonstrate that long-read metagenomic sequencing combined with metatranscriptomic analysis provides a direct view into the functional dynamics of BGCs in environmental processes and suggests a central role of secondary metabolites in maintaining phylogenetically conserved niches within biocrusts.Supplementary Data 1 : Description: Raw metagenome and metatranscriptome statistics.Supplementary Data 2 : Description: Assembly statistics of short- and long-read metagenomes as well as metatranscriptomes.Supplementary Data 3 : Description: Each biosynthetic gene cluster identified from the assembled metagenomes in this study.Supplementary Data 4 : Description: Each biosynthetic gene cluster identified in the metatranscriptomic assemblies.Supplementary Data 5 : Description: The genes used to calculate transcription of biosynthetic gene clusters and core bacterial genes.Supplementary Data 6 : Description: DESeq2 analysis of significantly transcribed genes between day and night-time transcription.Supplementary Data 7 : Description: Transcriptional scores for cation-related genes.Supplementary Data 8 : Description: Average abundance pattern for each phylum through time.Supplementary Data 9 : Description: Taxonomic composition of metagenomes and metatranscriptomes using fulllength 16S rRNA.Supplementary Data 10 : Description: Normalized sequence data showing scores of transcription at each time point with BGC type and Phylum shownThis work was partially supported by funds provided by the Office of Science Early Career Research Program Office of Biological and Environmental Research, of the U.S. Department of Energy and by the U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231 to Lawrence Berkeley National Laboratory. We also wish to acknowledge Simon Roux, Emiley Eloe-Fadrosh and Eoin Brodie for their constructive feedback.https://www.nature.com/commsbioam2022BiochemistryGeneticsMicrobiology and Plant Patholog

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Temperament Pathways to Childhood Disruptive Behavior and Adolescent Substance Abuse: Testing a Cascade Model

Abstract Temperament traits may increase risk for developmental psychopathology like Attention-Deficit/Hyperactivity Disorder (ADHD) and disruptive behaviors during childhood, as well as predisposing to substance abuse during adolescence. In the current study, a cascade model of trait pathways to adolescent substance abuse was examined. Component hypotheses were that (a) maladaptive traits would increase risk for inattention/hyperactivity, (b) inattention/hyperactivity would increase risk for disruptive behaviors, and (c) disruptive behaviors would lead to adolescent substance abuse. Participants were 674 children (486 boys) from 321 families in an ongoing, longitudinal high risk study that began when children were 3 years old. Temperament traits assessed were reactive control, resiliency, and negative emotionality, using examiner ratings on the California Q-Sort. Parent, teacher, and self ratings of inattention/hyperactivity, disruptive behaviors, and substance abuse were also obtained. Low levels of childhood reactive control, but not resiliency or negative emotionality, were associated with adolescent substance abuse, mediated by disruptive behaviors. Using a cascade model, family risk for substance abuse was partially mediated by reactive control, inattention/hyperactivity, and disruptive behavior. Some, but not all, temperament traits in childhood were related to adolescent substance abuse; these effects were mediated via inattentive/hyperactive and disruptive behaviors.This work was supported by NIAAA grant R01-AA12217 to Robert Zucker and Joel Nigg, NIAAA grant R37-AA07065 to Robert Zucker and Hiram Fitzgerald, and NIMH grant R01-MH59105 to Joel Nigg. Martel was supported by 1 F31 MH075533-01A2.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64507/1/#167, Martel 2009, Temperament path to disruptive behav and sub abuse JACP.pd

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

A cable-based series elastic actuator with conduit sensor for wearable exoskeletons

There is currently a scarcity of wearable robotic devices that can practically provide physical assistance in a range of real world activities. Soft wearable exoskeletons, or exosuits, have the potential to be more portable and less restrictive than their rigid counterparts. In this paper, we present the design of an actuation system that has been optimized for use in a soft exosuit for the human arm. The selected design comprises a DC motor and gearbox, a flexible cable conduit transmission, and a custom series elastic force sensor. Placed in series with the transmission conduit, the custom compliant force sensor consists of a translational steel compression spring with a pair of Hall effect sensors for measuring deflection. The custom sensor is validated as an accurate means of measuring cable tension, and it is shown that it can be used in feedback to control the cable tension with high bandwidth. The dynamic effect of the cable-conduit transmission on the force felt at the user interface is characterized by backdriving the system as it renders a range of virtual impedances to the user. We conclude with recommendations for the integration of such an actuation system into a full wearable exosuit