Hydrodynamic coupling in microbially mediated fracture mineralization : formation of self-organized groundwater flow channels

Evidence of fossilized microorganisms embedded within mineral veins and mineral-filled fractures has been observed in a wide range of geological environments. Microorganisms can act as sites for mineral nucleation and also contribute to mineral precipitation by inducing local geochemical changes. In this study, we explore fundamental controls on microbially induced mineralization in rock fractures. Specifically, we systematically investigate the influence of hydrodynamics (velocity, flow rate, aperture) on microbially mediated calcite precipitation. Our experimental results demonstrate that a feedback mechanism exists between the gradual reduction in fracture aperture due to precipitation, and its effect on the local fluid velocity. This feedback results in mineral fill distributions that focus flow into a small number of self-organizing channels that remain open, ultimately controlling the final aperture profile that governs flow within the fracture. This hydrodynamic coupling can explain field observations of discrete groundwater flow channeling within fracture-fill mineral geometries where strong evidence of microbial activity is reported

Chlorhexidine versus povidone–iodine skin antisepsis before upper limb surgery (CIPHUR) : an international multicentre prospective cohort study

Introduction Surgical site infection (SSI) is the most common and costly complication of surgery. International guidelines recommend topical alcoholic chlorhexidine (CHX) before surgery. However, upper limb surgeons continue to use other antiseptics, citing a lack of applicable evidence, and concerns related to open wounds and tourniquets. This study aimed to evaluate the safety and effectiveness of different topical antiseptics before upper limb surgery. Methods This international multicentre prospective cohort study recruited consecutive adults and children who underwent surgery distal to the shoulder joint. The intervention was use of CHX or povidone–iodine (PVI) antiseptics in either aqueous or alcoholic form. The primary outcome was SSI within 90 days. Mixed-effects time-to-event models were used to estimate the risk (hazard ratio (HR)) of SSI for patients undergoing elective and emergency upper limb surgery. Results A total of 2454 patients were included. The overall risk of SSI was 3.5 per cent. For elective upper limb surgery (1018 patients), alcoholic CHX appeared to be the most effective antiseptic, reducing the risk of SSI by 70 per cent (adjusted HR 0.30, 95 per cent c.i. 0.11 to 0.84), when compared with aqueous PVI. Concerning emergency upper limb surgery (1436 patients), aqueous PVI appeared to be the least effective antiseptic for preventing SSI; however, there was uncertainty in the estimates. No adverse events were reported. Conclusion The findings align with the global evidence base and international guidance, suggesting that alcoholic CHX should be used for skin antisepsis before clean (elective upper limb) surgery. For emergency (contaminated or dirty) upper limb surgery, the findings of this study were unclear and contradict the available evidence, concluding that further research is necessary

Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects

Objective Regular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.Methods Adult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.Results In this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p<0.0001).Conclusions Our findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease

Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease

BACKGROUND: Cardiac hypertrophic remodelling and systolic dysfunction are common in patients with mitochondrial disease and independent predictors of morbidity and early mortality. Endurance exercise training improves symptoms and skeletal muscle function, yet cardiac adaptations are unknown. METHODS AND RESULTS: Before and after 16-weeks of training, exercise capacity, cardiac magnetic resonance imaging and phosphorus-31 spectroscopy, disease burden, fatigue, quality of life, heart rate variability (HRV) and blood pressure variability (BPV) were assessed in 10 adult patients with m.3243A>G-related mitochondrial disease, and compared to age- and gender-matched sedentary control subjects. At baseline, patients had increased left ventricular mass index (LVMI, p < 0.05) and LV mass to end-diastolic volume ratio, and decreased longitudinal shortening and myocardial phosphocreatine/adenosine triphosphate ratio (all p < 0.01). Peak arterial–venous oxygen difference (p < 0.05), oxygen uptake (VO(2)) and power were decreased in patients (both p < 0.01) with no significant difference in cardiac power output. All patients remained stable and completed ≥ 80% sessions. With training, there were similar proportional increases in peak VO(2), anaerobic threshold and work capacity in patients and controls. LVMI increased in both groups (p < 0.01), with no significant effect on myocardial function or bioenergetics. Pre- and post-exercise training, HRV and BPV demonstrated increased low frequency and decreased high frequency components in patients compared to controls (all p < 0.05). CONCLUSION: Patients with mitochondrial disease and controls achieved similar proportional benefits of exercise training, without evidence of disease progression, or deleterious effects on cardiac function. Reduced exercise capacity is largely mediated through skeletal muscle dysfunction at baseline and sympathetic over-activation may be important in pathogenesis

Embedding collective leadership to foster collaborative inter-professional working in the care of older people (ECLECTIC): Study protocol [version 1; peer review: 2 approved]

Background: The National Integrated Care Programme for Older People (NICPOP), formerly NCPOP aims to support older people to live well in their homes by developing primary and secondary care services for older people, especially those with complex needs. The programme develops integrated intermediate care which traverses both hospital and community settings through multidisciplinary and interagency teams. This team-based approach to the integration of health services is a novel innovation in Irish health service delivery and will require, over time, a shift in cultures of care to allow for the development of competencies for inter-professional collaboration across the care continuum. The ECLECTIC project will develop an implementation framework for achieving, maintaining and monitoring competencies for interprofessional collaboration among multi-disciplinary teams charged with delivering care for older people across the continuum from acute to community settings.  Design: The ECLECTIC research design has been developed in collaboration with the NICPOP. In phase one of the project, a co-design team will collaborate to define and shape competencies for interprofessional collaboration. Phase two will involve the delivery of a collective leadership intervention over a 10-month period with multidisciplinary professionals working with older people across two geographical regions (Mullingar/Midlands and Beaumont/Dublin North). Each group will comprise of members of two multidisciplinary teams charged with coordinating and delivering care to older people across the continuum of acute to community care. Observations of collaborative inter-professional working will take place before, during, and after intervention. In phase three of the study, analysis of the interview and observation data will be presented to the co-design team in order to develop an implementation framework for future teams.  Discussion: The co-design process will develop core competencies and performance indicators for collaborative interprofessional working. The resulting implementation framework will be implemented nationally as part of the NICPOP.</p