Geospatial mapping and data linkage uncovers variability in outcomes of foot disease according to multiple deprivation: a population cohort study of people with diabetes

Aims/hypothesis: Our aim was to investigate the geospatial distribution of diabetic foot ulceration (DFU), lower extremity amputation (LEA) and mortality rates in people with diabetes in small geographical areas with varying levels of multiple deprivation. Methods: We undertook a population cohort study to extract the health records of 112,231 people with diabetes from the Scottish Care Information – Diabetes Collaboration (SCI-Diabetes) database. We linked this to health records to identify death, LEA and DFU events. These events were geospatially mapped using multiple deprivation maps for the geographical area of National Health Service (NHS) Greater Glasgow and Clyde. Tests of spatial autocorrelation and association were conducted to evaluate geographical variation and patterning, and the association between prevalence-adjusted outcome rates and multiple deprivation by quintile. Results: Within our health board region, people with diabetes had crude prevalence-adjusted rates for DFU of 4.6% and for LEA of 1.3%, and an incidence rate of mortality preceded by either a DFU or LEA of 10.5 per 10,000 per year. Spatial autocorrelation identified statistically significant hot spot (high prevalence) and cold spot (low prevalence) clusters for all outcomes. Small-area maps effectively displayed near neighbour clustering across the health board geography. Disproportionately high numbers of hot spots within the most deprived quintile for DFU (p < 0.001), LEA (p < 0.001) and mortality (p < 0.001) rates were found. Conversely, a disproportionately higher number of cold spots was found within the least deprived quintile for LEA (p < 0.001). Conclusions/interpretation: In people with diabetes, DFU, LEA and mortality rates are associated with multiple deprivation and form geographical neighbourhood clusters

Direct Estimation of the Mitochondrial DNA Mutation Rate in Drosophila melanogaster

Mitochondrial DNA (mtDNA) variants are widely used in evolutionary genetics as markers for population history and to estimate divergence times among taxa. Inferences of species history are generally based on phylogenetic comparisons, which assume that molecular evolution is clock-like. Between-species comparisons have also been used to estimate the mutation rate, using sites that are thought to evolve neutrally. We directly estimated the mtDNA mutation rate by scanning the mitochondrial genome of Drosophila melanogaster lines that had undergone approximately 200 generations of spontaneous mutation accumulation (MA). We detected a total of 28 point mutations and eight insertion-deletion (indel) mutations, yielding an estimate for the single-nucleotide mutation rate of 6.2 × 10−8 per site per fly generation. Most mutations were heteroplasmic within a line, and their frequency distribution suggests that the effective number of mitochondrial genomes transmitted per female per generation is about 30. We observed repeated occurrences of some indel mutations, suggesting that indel mutational hotspots are common. Among the point mutations, there is a large excess of G→A mutations on the major strand (the sense strand for the majority of mitochondrial genes). These mutations tend to occur at nonsynonymous sites of protein-coding genes, and they are expected to be deleterious, so do not become fixed between species. The overall mtDNA mutation rate per base pair per fly generation in Drosophila is estimated to be about 10× higher than the nuclear mutation rate, but the mitochondrial major strand G→A mutation rate is about 70× higher than the nuclear rate. Silent sites are substantially more strongly biased towards A and T than nonsynonymous sites, consistent with the extreme mutation bias towards A+T. Strand-asymmetric mutation bias, coupled with selection to maintain specific nonsynonymous bases, therefore provides an explanation for the extreme base composition of the mitochondrial genome of Drosophila

A thermosyphon-driven hydrothermal flow-through cell for in situ and time-resolved neutron diffraction studies

A flow-through cell for hydrothermal phase transformation studies by in situ and time-resolved neutron diffraction has been designed and constructed. The cell has a large internal volume of 320 ml and can operate at temperatures up to 573 K under autogenous vapor pressures (ca 8.5 106 Pa). The fluid flow is driven by a thermosyphon, which is achieved by the proper design of temperature difference around the closed loop. The main body of the cell is made of stainless steel (316 type), but the sample compartment is constructed from non-scattering Ti–Zr alloy. The cell has been successfully commissioned on Australia’s new high-intensity powder diffractometer WOMBAT at the Australian Nuclear Science and Technology Organization, using two simple phase transformation reactions from KAlSi2O6 (leucite) to NaAlSi2O6H2O (analcime) and then back from NaAlSi2O6H2O to KAlSi2O6 as examples. The demonstration proved that the cell is an excellent tool for probing hydrothermal crystallization. By collecting diffraction data every 5 min, it was clearly seen that KAlSi2O6 was progressively transformed to NaAlSi2O6H2O in a sodium chloride solution, and the produced NaAlSi2O6H2O was progressively transformed back to KAlSi2O6 in a potassium carbonate solution

Improving Outpatient Follow-Up After Hospitalization

Introduction: Hospital readmission is costly, in both patient quality of life and healthcare expenditures. Timely post-discharge follow-up has shown to reduce preventable readmissions. Efforts should be aimed at improving coordination of follow-ups. The aim of this quality improvement project was to increase post-hospital discharge follow-up by 20% for academic primary care patients admitted to a local tertiary care hospital by June 2020. This QI project was conducted at St. John Medical Center and the OU Internal Medicine Clinic utilizing Plan-Do-Study-Act methodology (PDSA). Patients admitted to OU inpatient teams who also designated OU Internal Medicine as their PCP were included in the study. An EMR query was utilized to measure follow-ups completed within 14 days of discharge. A process map was made, showing intervention points. Gap Analysis/Scatter Diagram was used to show points of largest impact. Methods: PDSA #1: Senior residents were given access to AllScripts (the clinic EMR scheduling program) to directly schedule patient follow-up appointments within 14 days of discharge. Follow-up appointments were included in patients’ discharge paperwork.    PDSA #2: Prior to discharge, patients were screened by care managers for a follow-up home visit. If appropriate, a multidisciplinary team of providers conducted an onsite follow-up visit within 14 days of discharge. Results: After PDSA #1: Residents surveyed after the first PDSA cycle admitted feeling overwhelmed with additional tasks and inconsistently scheduled appointments in AllScripts. In addition, EMR review demonstrated a high no-show rate for patients with follow-up appointments. Due to these results, we sought alternative options. After PDSA #2: Three patients were visited in their homes for an onsite 14-day follow-up appointment. Unfortunately, this process was put on hold given the COVID outbreak. At baseline, 31.6% of patients discharged from the hospital attended post-discharge follow-up visit within 14 days. This percentage declined to 29.2% after our interventions. Conclusion: The low rate of hospital discharge appointments within two weeks of discharge indicates that many patients are lacking crucial follow-up care. This project found that having residents enter appointments directly into AllScripts and performing home visits within 14 days of discharge made no difference in the overall rate of successful post-discharge follow-up visits. Weaknesses of this study include but are not limited to the gap of data between July 2019 and March 2020 and the small number of home visits that were performed. This project confirms the concern that unless new approaches to significant post-discharge follow-up barriers are considered, increasing the percentage of successful follow-up appointments will remain a difficult task

Return of non-ACMG recommended incidental genetic findings to pediatric patients: Considerations and opportunities from experiences in genomic sequencing

BACKGROUND: The uptake of exome/genome sequencing has introduced unexpected testing results (incidental findings) that have become a major challenge for both testing laboratories and providers. While the American College of Medical Genetics and Genomics has outlined guidelines for laboratory management of clinically actionable secondary findings, debate remains as to whether incidental findings should be returned to patients, especially those representing pediatric populations. METHODS: The Sequencing Analysis and Diagnostic Yield working group in the Clinical Sequencing Evidence-Generating Research Consortium has collected a cohort of pediatric patients found to harbor a genomic sequencing-identified non-ACMG-recommended incidental finding. The incidental variants were not thought to be associated with the indication for testing and were disclosed to patients and families. RESULTS: In total, 23 non-ACMG-recommended incidental findings were identified in 21 pediatric patients included in the study. These findings span four different research studies/laboratories and demonstrate differences in incidental finding return rate across study sites. We summarize specific cases to highlight core considerations that surround identification and return of incidental findings (uncertainty of disease onset, disease severity, age of onset, clinical actionability, and personal utility), and suggest that interpretation of incidental findings in pediatric patients can be difficult given evolving phenotypes. Furthermore, return of incidental findings can benefit patients and providers, but do present challenges. CONCLUSIONS: While there may be considerable benefit to return of incidental genetic findings, these findings can be burdensome to providers and present risk to patients. It is important that laboratories conducting genomic testing establish internal guidelines in anticipation of detection. Moreover, cross-laboratory guidelines may aid in reducing the potential for policy heterogeneity across laboratories as it relates to incidental finding detection and return. However, future discussion is required to determine whether cohesive guidelines or policy statements are warranted

Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region

Establishment of wMel Wolbachia in Aedes aegypti mosquitoes and reduction of local dengue transmission in Cairns and surrounding locations in northern Queensland, Australia.

Background: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and subsequently shown in laboratory studies to reduce transmission of a range of viruses including dengue, Zika, chikungunya, yellow fever, and Mayaro viruses that cause human disease. Here we report the entomological and epidemiological outcomes of staged deployment of Wolbachia across nearly all significant dengue transmission risk areas in Australia. Methods: The  wMel strain of  Wolbachia was backcrossed into the local  Aedes aegypti genotype (Cairns and Townsville backgrounds) and mosquitoes were released in the field by staff or via community assisted methods. Mosquito monitoring was undertaken and mosquitoes were screened for the presence of  Wolbachia. Dengue case notifications were used to track dengue incidence in each location before and after releases. Results: Empirical analyses of the Wolbachia mosquito releases, including data on the density, frequency and duration of Wolbachia mosquito releases, indicate that Wolbachia can be readily established in local mosquito populations, using a variety of deployment options and over short release durations (mean release period 11 weeks, range 2-22 weeks). Importantly, Wolbachia frequencies have remained stable in mosquito populations since releases for up to 8 years. Analysis of dengue case notifications data demonstrates near-elimination of local dengue transmission for the past five years in locations where Wolbachia has been established. The regression model estimate of Wolbachia intervention effect from interrupted time series analyses of case notifications data prior to and after releases, indicated a 96% reduction in dengue incidence in Wolbachia treated populations (95% confidence interval: 84 - 99%). Conclusion: Deployment of the wMel strain of Wolbachia into local Ae. aegypti populations across the Australian regional cities of Cairns and most smaller regional communities with a past history of dengue has resulted in the reduction of local dengue transmission across all deployment areas

Photochemistry in biomass burning plumes and implications for tropospheric ozone over the tropical South Atlantic

Photochemistry occuring in biomass burning plumes over the tropical south Atlantic is analyzed using data collected during the Transport and Atmospheric Chemistry Near the Equator‐Atlantic aircraft expedition conducted during the tropical dry season in September 1992 and a photochemical point model. Enhancement ratios (ΔY/ΔX, where Δ indicates the enhancement of a compound in the plume above the local background mixing ratio, Y are individual hydrocarbons, CO, O3, N2O, HNO3, peroxyacetyl nitrate (PAN), CH2O, acetone, H2O2, CH3OOH, HCOOH, CH3COOH or aerosols and X is CO or CO2) are reported as a function of plume age inferred from the progression of Δnon‐methane hydrocarbons/ΔCO enhancement ratios. Emission, formation, and loss of species in plumes can be diagnosed from progression of enhancement ratios from fresh to old plumes. O3 is produced in plumes over at least a 1 week period with mean ΔO3/ΔCO = 0.7 in old plumes. However, enhancement ratios in plumes can be influenced by changing background mixing ratios and by photochemical loss of CO. We estimate a downward correction of ∼20% in enhancement ratios in old plumes relative to ΔCO to correct for CO loss. In a case study of a large persistent biomass burning plume at 4‐km we found elevated concentrations of PAN in the fresh plume. The degradation of PAN helped maintain NOx mixing ratios in the plume where, over the course of a week, PAN was converted to HNO3. Ozone production in the plume was limited by the availability of NOx, and because of the short lifetime of O3 at 4‐km, net ozone production in the plume was negligible. Within the region, the majority of O3 production takes place in air above median CO concentration, indicating that most O3 production occurs in plumes. Scaling up from the mean observed ΔO3/ΔCO in old plumes, we estimate a minimum regional O3 production of 17×1010molecules O3 cm−2 s−1. This O3 production rate is sufficient to fully explain the observed enhancement in tropospheric O3 over the tropical South Atlantic during the dry season

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes