Measuring the quality and quantity of professional intrapartum support: Testing a computerised systematic observation tool in the clinical setting

Background: Continuous support in labour has a significant impact on a range of clinical outcomes, though whether the quality and quantity of support behaviours affects the strength of this impact has not yet been established. To identify the quality and quantity of support, a reliable means of measurement is needed. To this end, a new computerised systematic observation tool, the ‘SMILI' (Supportive Midwifery in Labour Instrument) was developed. The aim of the study was to test the validity and usability of the ‘Supportive Midwifery in Labour Instrument' (SMILI) and to test the feasibility and acceptability of the systematic observation approach in the clinical intrapartum setting. Methods: Systematic observation was combined with a postnatal questionnaire and the collection of data about clinical processes and outcomes for each observed labour. The setting for the study was four National Health Service maternity units in Scotland, UK. Participants in this study were forty five midwives and forty four women. The SMILI was used by trained midwife observers to record labour care provided by midwives. Observations were undertaken for an average of two hours and seventeen minutes during the active first stage of labour and, in 18 cases, the observation included the second stage of labour. Content validity of the instrument was tested by the observers, noting the extent to which the SMILI facilitated the recording of all key aspects of labour care and interactions. Construct validity was tested through exploration of correlations between the data recorded and women's feelings about the support they received. Feasibility and usability data were recorded following each observation by the observer. Internal reliability and construct validity were tested through statistical analysis of the data. Results: One hundred and four hours of labour care were observed and recorded using the SMILI during forty nine labour episodes. Conclusion: The SMILI was found to be a valid and reliable instrument in the intrapartum setting in which it was tested. The study identified that the SMILI could be used to test correlations between the quantity and quality of support and outcomes. The systematic observational approach was found to be an acceptable and feasible method of enquiry

Multi-decadal changes in tundra environments and ecosystems: Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF).

Understanding the responses of tundra systems to global change has global implications. Most tundra regions lack sustained environmental monitoring and one of the only ways to document multi-decadal change is to resample historic research sites. The International Polar Year (IPY) provided a unique opportunity for such research through the Back to the Future (BTF) project (IPY project #512). This article synthesizes the results from 13 papers within this Ambio Special Issue. Abiotic changes include glacial recession in the Altai Mountains, Russia; increased snow depth and hardness, permafrost warming, and increased growing season length in sub-arctic Sweden; drying of ponds in Greenland; increased nutrient availability in Alaskan tundra ponds, and warming at most locations studied. Biotic changes ranged from relatively minor plant community change at two sites in Greenland to moderate change in the Yukon, and to dramatic increases in shrub and tree density on Herschel Island, and in sub-arctic Sweden. The population of geese tripled at one site in northeast Greenland where biomass in non-grazed plots doubled. A model parameterized using results from a BTF study forecasts substantial declines in all snowbeds and increases in shrub tundra on Niwot Ridge, Colorado over the next century. In general, results support and provide improved capacities for validating experimental manipulation, remote sensing, and modeling studies

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Metabolic alterations during the growth of tumour spheroids

Solid tumours undergo considerable alterations in their metabolism of nutrients in order to generate sufficient energy and biomass for sustained growth and proliferation. During growth, the tumour microenvironment exerts a number of influences (e.g. hypoxia and acidity) that affect cellular biology and the flux or utilisation of fuels including glucose. The tumour spheroid model was used to characterise the utilisation of glucose and describe alterations to the activity and expression of key glycolytic enzymes during the tissue growth curve. Glucose was avidly consumed and associated with the production of lactate and an acidified medium, confirming the reliance on glycolytic pathways and a diminution of oxidative phosphorylation. The expression levels and activities of hexokinase, phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the glycolytic pathway were measured to assess glycolytic capacity. Similar measurements were made for glucose-6-phosphate dehydrogenase, the entry point and regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate dehydrogenase, a key link to TCA cycle intermediates. The parameters for these key enzymes were shown to undergo considerable variation during the growth curve of tumour spheroids. In addition, they revealed that the dynamic alterations were influenced by both transcriptional and posttranslational mechanisms

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Constructing and identifying predictors of frailty among homeless adults—A latent variable structural equations model approach

Homeless urbanites are a heterogeneous population with unique health and social service needs. The study examined situational, behavioral, health-related and resource indicators in terms of their direct impact on frailty, hypothesized as a latent variable. Using structural equation modeling (SEM), a model was tested with 150 homeless men and women, ages 40–73, from three homeless day center drop-in sites on Skid Row and one residential drug treatment (RDT) facility that works with homeless parolees and probationers. In bivariate analyses with the latent construct frailty, months homeless (p < 0.01), female gender (p < 0.05), education (p < 0.05), comorbid conditions (p < 0.001), nutrition (p < 0.001), resilience (p < 0.001), health care utilization (p < 0.01), and falls (p < 0.001) were significantly associated with frailty. In the final path model, significant predictors of frailty included educational attainment (p < 0.01), comorbid conditions (p < 0.001), nutrition (p < 0.001), resilience (p < 0.001), and falls (p < 0.01). These findings will serve as a foundation for future nurse-led, community-based initiatives that focus on key predictors of frailty among the homeless and the development of interventions