Modeling the architecture of the regulatory system controlling methylenomycin production in Streptomyces coelicolor

The antibiotic methylenomycin A is produced naturally by Streptomyces coelicolor A3(2), a model organism for streptomycetes. This compound is of particular interest to synthetic biologists because all of the associated biosynthetic, regulatory and resistance genes are located on a single cluster on the SCP1 plasmid, making the entire module easily transferable between different bacterial strains. Understanding further the regulation and biosynthesis of the methylenomycin producing gene cluster could assist in the identification of motifs that can be exploited in synthetic regulatory systems for the rational engineering of novel natural products and antibiotics

Lunar-sourced GEO Powersats: An Integrated ISRU System

Solar power satellites (powersats) can be built almost entirely from lunar resources. When C-class asteroids are also included as ore bodies a complete powersat can be built through insitu resource utilization (ISRU) given appropriate processing and transportation technology.This article provides an in-depth overview of the technical feasibility and economic viabilityof lunar construction and operations for powersat component construction and delivery togeostationary earth orbit (GEO). Techno-economic analysis suggests a return on investmentin seven years assuming a three percent discount rate. Electrical power collected in GEO andbeamed to terrestrial receivers by the powersats can be sold as baseload power in the wholesale electricity market to generate revenue. This work presents a complete concept of operationsfrom initial rocket launches to regolith harvesting through transport to GEO. Lunarinfrastructure can be constructed of modules to optimize size and weight for launch costs.Future growth can be derived from using ISRU to build additional processing bases. A scale-up in this manner can provide 22% of the world’s energy needs by the end of a 20-year period.This work builds upon previous studies and completes the architectural description ofpredominantly lunar-sourced GEO powersats

Human-GDPR Interaction: Practical Experiences of Accessing Personal Data

In our data-centric world, most services rely on collecting and using personal data. The EU's General Data Protection Regulation (GDPR) aims to enhance individuals’ control over their data, but its practical impact is not well understood. We present a 10-participant study, where each participant filed 4-5 data access requests. Through interviews accompanying these requests and discussions scrutinising returned data, it appears that GDPR falls short of its goals due to non-compliance and low-quality responses. Participants found their hopes to understand providers’ data practices or harness their own data unmet. This causes increased distrust without any subjective improvement in power, although more transparent providers do earn greater trust. We propose designing more effective, data-inclusive and open policies and data access systems to improve both customer relations and individual agency, and also that wider public use of GDPR rights could help with delivering accountability and motivating providers to improve data practices

Why aspect graphs are not (yet) practical for computer vision

A panel discussion on the theme of this report was organized for the 1991 IEEE Workshop on Directions in Automated CAD-Based Vision. This report contains the revised comments of the panel discussion participants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30175/1/0000560.pd

Psychological distress, depression, anxiety and life satisfaction following COVID-19 infection: Evidence from 11 UK longitudinal population studies

Background: Evidence on associations between COVID-19 illness and mental health is mixed. We aimed to examine whether COVID-19 is associated with deterioration in mental health while considering pre-pandemic mental health, time since infection, subgroup differences, and confirmation of infection via self-reported test and serology data. Methods: We obtained data from 11 UK longitudinal studies with repeated measures of mental health (psychological distress, depression, anxiety, and life satisfaction; mental health scales were standardised within each study across time) and COVID-19 status between April, 2020, and April, 2021. We included participants with information available on at least one mental health outcome measure and self-reported COVID-19 status (suspected or test-confirmed) during the pandemic, and a subset with serology-confirmed COVID-19. Furthermore, only participants who had available data on a minimum set of covariates, including age, sex, and pre-pandemic mental health were included. We investigated associations between having ever had COVID-19 and mental health outcomes using generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education, and pre-pandemic mental health, whether the strength of the association varied according to time since infection, and whether associations differed between self-reported versus confirmed (by test or serology) infection. Findings: Between 21 Dec, 2021, and July 11, 2022, we analysed data from 54 442 participants (ranging from a minimum age of 16 years in one study to a maximum category of 90 years and older in another; including 33 200 [61·0%] women and 21 242 [39·0%] men) from 11 longitudinal UK studies. Of 40 819 participants with available ethnicity data, 36 802 (90·2%) were White. Pooled estimates of standardised differences in outcomes suggested associations between COVID-19 and subsequent psychological distress (0·10 [95% CI 0·06 to 0·13], I2=42·8%), depression (0·08 [0·05 to 0·10], I2=20·8%), anxiety (0·08 [0·05 to 0·10], I2=0·0%), and lower life satisfaction (–0·06 [–0·08 to –0·04], I2=29·2%). We found no evidence of interactions between COVID-19 and sex, education, ethnicity, or pre-pandemic mental health. Associations did not vary substantially between time since infection of less than 4 weeks, 4–12 weeks, and more than 12 weeks, and were present in all age groups, with some evidence of stronger effects in those aged 50 years and older. Participants who self-reported COVID-19 but had negative serology had worse mental health outcomes for all measures than those without COVID-19 based on serology and self-report. Participants who had positive serology but did not self-report COVID-19 did not show association with mental health outcomes. Interpretation: Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings emphasise the need for greater post-infection mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. Funding: UK Medical Research Council and UK National Institute for Health and Care Research

Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors

SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. From cross-sectional antibody testing of 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies (jointly in April-May 2021, and TwinsUK only in November 2021-January 2022), we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables. Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months, compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK "Shielded Patient List" had consistently greater odds (2 to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies

Characteristics of Indigenous primary health care service delivery models: a systematic scoping review

Published online: 25 January 2018Background: Indigenous populations have poorer health outcomes compared to their non-Indigenous counterparts. The evolution of Indigenous primary health care services arose from mainstream health services being unable to adequately meet the needs of Indigenous communities and Indigenous peoples often being excluded and marginalised from mainstream health services. Part of the solution has been to establish Indigenous specific primary health care services, for and managed by Indigenous peoples. There are a number of reasons why Indigenous primary health care services are more likely than mainstream services to improve the health of Indigenous communities. Their success is partly due to the fact that they often provide comprehensive programs that incorporate treatment and management, prevention and health promotion, as well as addressing the social determinants of health. However, there are gaps in the evidence base including the characteristics that contribute to the success of Indigenous primary health care services in providing comprehensive primary health care. This systematic scoping review aims to identify the characteristics of Indigenous primary health care service delivery models. Method: This systematic scoping review was led by an Aboriginal researcher, using the Joanna Briggs Institute Scoping Review Methodology. All published peer-reviewed and grey literature indexed in PubMed, EBSCO CINAHL, Embase, Informit, Mednar, and Trove databases from September 1978 to May 2015 were reviewed for inclusion. Studies were included if they describe the characteristics of service delivery models implemented within an Indigenous primary health care service. Sixty-two studies met the inclusion criteria. Data were extracted and then thematically analysed to identify the characteristics of Indigenous PHC service delivery models. Results: Culture was the most prominent characteristic underpinning all of the other seven characteristics which were identified – accessible health services, community participation, continuous quality improvement, culturally appropriate and skilled workforce, flexible approach to care, holistic health care, and self-determination and empowerment. Conclusion: While the eight characteristics were clearly distinguishable within the review, the interdependence between each characteristic was also evident. These findings were used to develop a new Indigenous PHC Service Delivery Model, which clearly demonstrates some of the unique characteristics of Indigenous specific models.Stephen G. Harfield, Carol Davy, Alexa McArthur, Zachary Munn, Alex Brown and Ngiare Brow

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication