Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays

Background: We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations). The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. Findings: In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. Conclusions: Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred

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

Promoting social inclusion: emerging evidence from the Catalyst-Clemente program

Catalyst-Clemente is an innovative educational program based upon a collaboration involving Australian Catholic University, Mission Australia and the St Vincent de Paul Society. The program enhances the transformational learning opportunities and re-engagement of disadvantaged people within the community. This paper reports on the origins and rationale of the program and initial research undertaken with the students. Six key themes of self, social interaction, relationships with others, learning, community participation and the future have been identified that represent the ways in which the program impacts upon the participants. The initial study suggests that Catalyst-Clemente is a practical educational solution that has resulted in enhancing the life opportunities and choices for disadvantaged Australians

Participatory planning for local sustainability guided by the Sustainable Development Goals

To achieve the United Nations Sustainable Development Goals (SDGs), actions are required at all global, national, and local scales. To ensure coordination between scales, local actions need to be carefully planned to be aligned with global and national priorities. Local planning for sustainability must be adaptive and heterogeneous but also consistent and driven by the community. We describe an approach to co-create a local sustainability plan using the SDGs for a rural community in southeastern Australia using participatory techniques for co-creation, data collection, and review. The community placed a high priority on infrastructure for achieving sustainable growth and social equity while preserving their unique environment. By articulating their priorities in this community-led plan, the community is empowered to advocate for the sustainable development of their town with decision makers and funding bodies. If local communities create sustainability plans using the SDGs, then such planning will be consistent between and across geographic scales, and aligned with the global goals. This will also aid in achievement of the SDGs at national and global scales, as advocated by the United Nations in the 2030 Agenda for Sustainable Development

Modification of social determinants of health by critical illness and consequences of that modification for recovery: an international qualitative study.

OBJECTIVES: Social determinants of health (SDoH) contribute to health outcomes. We identified SDoH that were modified by critical illness, and the effect of such modifications on recovery from critical illness. DESIGN: In-depth semistructured interviews following hospital discharge. Interview transcripts were mapped against a pre-existing social policy framework: money and work; skills and education; housing, transport and neighbourhoods; and family, friends and social connections. SETTING: 14 hospital sites in the USA, UK and Australia. PARTICIPANTS: Patients and caregivers, who had been admitted to critical care from three continents. RESULTS: 86 interviews were analysed (66 patients and 20 caregivers). SDoH, both financial and non-financial in nature, could be negatively influenced by exposure to critical illness, with a direct impact on health-related outcomes at an individual level. Financial modifications included changes to employment status due to critical illness-related disability, alongside changes to income and insurance status. Negative health impacts included the inability to access essential healthcare and an increase in mental health problems. CONCLUSIONS: Critical illness appears to modify SDoH for survivors and their family members, potentially impacting recovery and health. Our findings suggest that increased attention to issues such as one's social network, economic security and access to healthcare is required following discharge from critical care

Revealing the spatial variability of water fluxes at the groundwater-surface water interface

There is widespread recognition that the groundwater-surface water interface can have significant influence on the pattern and form of the transfer of nutrient-rich groundwater to rivers. Characterizing and quantifying this influence is critical for successful management of water resources in many catchments, particularly those threatened by rising nitrate levels in groundwater. Building on previous experimental investigations in one such catchment: the River Leith, UK, we report on a multimeasurement, multiscale program aimed at developing a conceptualization of groundwater-surface water flow pathways along a 200 m reach. Key to this conceptualization is the quantification of vertical and horizontal water fluxes, which is achieved through a series of Darcian flow estimates coupled with in-stream piezometer tracer dilution tests. These data, enhanced by multilevel measurements of chloride concentration in riverbed pore water and water-borne geophysical surveying, reveal a contrast in the contribution of flow components along the reach. In the upper section of the reach, a localized connectivity to regional groundwater, that appears to suppress the hyporheic zone, is identified. Further downstream, horizontal (lateral and longitudinal) flows appear to contribute more to the total subsurface flow at the groundwater-surface water interface. Although variation in hydraulic conductivity of the riverbed is observed, localized variation that can account for the spatial variability in flow pathways is not evident. The study provides a hydrological conceptualization for the site, which is essential for future studies which address biogeochemical processes, in relation to nitrogen retention/release. Such a conceptualization would not have been possible without a multiexperimental program