Do influenza and pneumococcal vaccines prevent community-acquired respiratory infections among older people with diabetes and does this vary by chronic kidney disease? A cohort study using electronic health records

Objective: We aimed to estimate the effectiveness of influenza and 23-valent pneumococcal polysaccharide vaccination on reducing the burden of community-acquired lower respiratory tract infection (LRTI) among older people with diabetes, and whether this varied by chronic kidney disease status. Research design and methods: We used linked UK electronic health records for a retrospective cohort study of 190,492 patients ≥65 years with diabetes mellitus and no history of renal replacement therapy, 1997–2011. We included community-acquired LRTIs managed in primary or secondary care. Infection incidence rate ratios were estimated using Poisson regression. Pneumococcal vaccine effectiveness (VE) was calculated as (1 – effect measure). To estimate influenza VE a ratio-of-ratios analysis (winter effectiveness/summer effectiveness) was used to address confounding by indication. Final VE estimates were stratified according to estimated glomerular filtration rate and proteinuria status. Results: Neither influenza nor pneumococcal vaccine uptake varied according to CKD status. Pneumococcal VE was 22% (95%CI: 11–31) against community-acquired pneumonia for the first year after vaccination, but was negligible after five years. In the ratio-of-ratios analysis, current influenza vaccination had 7% effectiveness for preventing community-acquired LRTI (95%CI: 3–12). Pneumococcal vaccine effectiveness was lower among patients with a history of proteinuria than among patients without proteinuria (p=0.04), but otherwise this study did not identify variation in pneumococcal or influenza VE by markers of CKD. Conclusions: The public health benefits of influenza vaccine may be modest among older people with diabetes. Pneumococcal vaccination protection against community-acquired pneumonia declines swiftly: alternative vaccination schedules should be investigated

Acute kidney injury in stable COPD and at exacerbation.

BACKGROUND: While acute kidney injury (AKI) alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known. METHODS: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics) in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107) and identified confounding factors. RESULTS: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03) increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free. CONCLUSION: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome

Measurement of 222Rn dissolved in water at the Sudbury Neutrino Observatory

The technique used at the Sudbury Neutrino Observatory (SNO) to measure the concentration of 222Rn in water is described. Water from the SNO detector is passed through a vacuum degasser (in the light water system) or a membrane contact degasser (in the heavy water system) where dissolved gases, including radon, are liberated. The degasser is connected to a vacuum system which collects the radon on a cold trap and removes most other gases, such as water vapor and nitrogen. After roughly 0.5 tonnes of H2O or 6 tonnes of D2O have been sampled, the accumulated radon is transferred to a Lucas cell. The cell is mounted on a photomultiplier tube which detects the alpha particles from the decay of 222Rn and its daughters. The overall degassing and concentration efficiency is about 38% and the single-alpha counting efficiency is approximately 75%. The sensitivity of the radon assay system for D2O is equivalent to ~3 E(-15) g U/g water. The radon concentration in both the H2O and D2O is sufficiently low that the rate of background events from U-chain elements is a small fraction of the interaction rate of solar neutrinos by the neutral current reaction.Comment: 14 pages, 6 figures; v2 has very minor change

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations

Building development and roads: implications for the distribution of stone curlews across the Brecks

Background: Substantial new housing and infrastructure development planned within England has the potential to conflict with the nature conservation interests of protected sites. The Breckland area of eastern England (the Brecks) is designated as a Special Protection Area for a number of bird species, including the stone curlew (for which it holds more than 60% of the UK total population). We explore the effect of buildings and roads on the spatial distribution of stone curlew nests across the Brecks in order to inform strategic development plans to avoid adverse effects on such European protected sites. Methodology: Using data across all years (and subsets of years) over the period 1988 – 2006 but restricted to habitat areas of arable land with suitable soils, we assessed nest density in relation to the distances to nearest settlements and to major roads. Measures of the local density of nearby buildings, roads and traffic levels were assessed using normal kernel distance-weighting functions. Quasi-Poisson generalised linear mixed models allowing for spatial auto-correlation were fitted. Results: Significantly lower densities of stone curlew nests were found at distances up to 1500m from settlements, and distances up to 1000m or more from major (trunk) roads. The best fitting models involved optimally distance-weighted variables for the extent of nearby buildings and the trunk road traffic levels. Significance : The results and predictions from this study of past data suggests there is cause for concern that future housing development and associated road infrastructure within the Breckland area could have negative impacts on the nesting stone curlew population. Given the strict legal protection afforded to the SPA the planning and conservation bodies have subsequently agreed precautionary restrictions on building development within the distances identified and used the modelling predictions to agree mitigation measures for proposed trunk road developments

Ecology of domestic dogs canis familiaris as an emerging reservoir of Guinea worm dracunculus medinensis infection

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: Data are available at Dryad data repository https://doi.org/10.5061/dryad.vx0k6djnh.Global eradication of human Guinea worm disease (dracunculiasis) has been set back by the emergence of infections in animals, particularly domestic dogs Canis familiaris. The ecology and epidemiology of this reservoir is unknown. We tracked dogs using GPS, inferred diets using stable isotope analysis and analysed correlates of infection in Chad, where numbers of Guinea worm infections are greatest. Dogs had small ranges that varied markedly among villages. Diets consisted largely of human staples and human faeces. A minority of ponds, mostly <200 m from dog-owning households, accounted for most dog exposure to potentially unsafe water. The risk of a dog having had Guinea worm was reduced in dogs living in households providing water for animals but increased with increasing fish consumption by dogs. Provision of safe water might reduce dog exposure to unsafe water, while prioritisation of proactive temephos (Abate) application to the small number of ponds to which dogs have most access is recommended. Fish might have an additional role as transport hosts for Guinea worm, by concentrating copepods infected with worm larvae.Chad Ministry of Public HealthWorld Health OrganizationCarter Cente

Smc5/6: a link between DNA repair and unidirectional replication?

Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity

Four small puzzles that Rosetta doesn't solve

A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular "puzzles" should serve as useful model systems for developers wishing to make foundational improvements to this powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special Collectio

Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients