The Kanyakla study: Randomized controlled trial of a microclinic social network intervention for promoting engagement and retention in HIV care in rural western Kenya

BACKGROUND: Existing social relationships are a potential source of social capital that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based \u27microclinic\u27 intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness. METHODS: In nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on disengagement from care (≥90-day absence from care after a missed visit) and the proportion of time patients were adherent to clinic visits (\u27time-in-care\u27). We also evaluated changes in social support, HIV status disclosure, and HIV-associated stigma. RESULTS: Of 350 eligible patients, 304 (87%) enrolled, with 154 randomized to intervention and 150 to control. Over one year of follow-up, disengagement from care was similar in intervention and control (18% vs 17%, hazard ratio 1.03, 95% CI 0.61-1.75), as was time-in-care (risk difference -2.8%, 95% CI -10.0% to +4.5%). The intervention improved social support for attending clinic appointments (+0.4 units on 5-point scale, 95% CI 0.08-0.63), HIV status disclosure to close social supports (+0.3 persons, 95% CI 0.2-0.5), and reduced stigma (-0.3 units on 5-point scale, 95% CI -0.40 to -0.17). CONCLUSIONS: The data from our pragmatic randomized trial in rural western Kenya are compatible with the null hypothesis of no difference in HIV care engagement between those who participated in a microclinic intervention and those who did not, despite improvements in proposed intervention mechanisms of action. However, some benefit or harm cannot be ruled out because the confidence intervals were wide. Results differ from a prior quasi-experimental pilot study, highlighting important implementation considerations when evaluating complex social interventions for HIV care. TRIAL REGISTRATION: Clinical trial number: NCT02474992

Organization of the human intestine at single-cell resolution

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall healt

Thermally induced magnetization dynamics of optically excited YIG/Cu/Ni81Fe19 trilayers

This is the final version of the article. Available from American Physical Society via the DOI in this record.The response of Y3Fe5O12/Cu/Ni81Fe19 trilayer structures to excitation by a femtosecond laser pulse has been studied in optical pump-probe experiments and compared with the response of Y3Fe5O12 (YIG) and Ni81Fe19 reference samples. The optical pump induces a partial demagnetization of the Ni81Fe19, a large thermal gradient within the YIG, and temperature differences across the interfaces within the sample stack. When a moderate magnetic field is applied close to normal to the sample plane, so as to quasialign the YIG magnetization with the field and cant the Ni81Fe19 magnetization from the plane, ultrafast demagnetization initiates precession of the Ni81Fe19 magnetization. The transient temperature profile within the samples has been modeled using a one-dimensional finite-element computational model of heat conduction, while the magnetization dynamics are well described by a macrospin solution of the Landau-Lifshitz-Gilbert equation. The precessional response of the Ni81Fe19 layers within the trilayers and the Ni81Fe19 reference sample are very similar for pump fluences of up to 1.5 mJ/cm2, beyond which irreversible changes to the magnetic properties of the films are observed. These results suggest that the spin Seebeck effect is ineffective in modifying the precessional dynamics of the present YIG/Cu/Ni81Fe19 samples when subject to ultrafast optical excitation.The authors gratefully acknowledge financial support from Engineering and Physical Sciences Research Council Grant No. EP/J018767/1 and an EPSRC CASE award with Dr. D. Williams of Hitachi Cambridge. H.J.M. acknowledges financial support in the form of a scholarship from “The Establishment of Martyrs of Iraq.

Depression in Mid- and Later-Life and Risk of Dementia in Women: A Prospective Study within the Danish Nurses Cohort

BACKGROUND: Depression and dementia confer substantial global health burdens, particularly in women. Understanding the association between depression and dementia may inform new targets for prevention and/or early intervention. OBJECTIVE: To investigate the association between depression in mid- and later-life and dementia (all-cause, Alzheimer's disease (AD) or vascular dementia (VaD)) in women. METHODS: A prospective study design. Nurses were followed from age 60 years or entry into the cohort, whichever came last, until date of dementia, death, emigration, or end of follow-up, whichever came first. Cox regression models with age as the underlying timeline were used to estimate the associations between time-varying depression and incident dementia. RESULTS: The study included 25,651 female Danish nurses (≥45 years) participating in the Danish Nurse Cohort. During an average of 23 years of follow-up, 1,232 (4.8%) nurses developed dementia and 8,086 (31.5%) were identified with at least two episodes of treated depression. In adjusted analyses, nurses with depression were at a statistically significant 5.23-fold higher risk of all-cause dementia (aHR 5.23:95% CI, 4.64-5.91) compared to those with no history of depression. The differential effects of depression were greater for VaD (aHR 7.96:95% CI, 5.26-12.0) than AD (aHR 4.64:95% CI, 3.97-5.42). Later life depression (>60 years) (aHR 5.85:95% CI, 5.17-6.64) and recurrent depression (aHR 3.51:95% CI, 2.67-4.61) elevated dementia risk. Severe depression tripled the risk of all cause dementia (aHR 3.14:95% CI, 2.62-3.76). CONCLUSION: Both later life and severe depression substantially increase dementia risk in women, particularly VaD

Changes in urinary metabolomic profile during relapsing renal vasculitis

Current biomarkers of renal disease in systemic vasculitis lack predictive value and are insensitive to early damage. To identify novel biomarkers of renal vasculitis flare, we analysed the longitudinal urinary metabolomic profile of a rat model of anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. Wistar-Kyoto (WKY) rats were immunised with human myeloperoxidase (MPO). Urine was obtained at regular intervals for 181 days, after which relapse was induced by re-challenge with MPO. Urinary metabolites were assessed in an unbiased fashion using nuclear magnetic resonance (NMR) spectroscopy, and analysed using partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLS-R). At 56 days post-immunisation, we found that rats with vasculitis had a significantly different urinary metabolite profile than control animals; the observed PLS-DA clusters dissipated between 56 and 181 days, and re-emerged with relapse. The metabolites most altered in rats with active or relapsing vasculitis were trimethylamine N-oxide (TMAO), citrate and 2-oxoglutarate. Myo-inositol was also moderately predictive. The key urine metabolites identified in rats were confirmed in a large cohort of patients using liquid chromatography-mass spectrometry (LC-MS). Hypocitraturia and elevated urinary myo-inositol remained associated with active disease, with the urine myo-inositol:citrate ratio being tightly correlated with active renal vasculitis

A comparative study of free oligosaccharides in the milk of domestic animals

This study was conducted to provide a comprehensive analysis of the oligosaccharides in the milk of a variety of important domestic animals including cow, goat, sheep, pig, horse, and dromedary camel. Using an analytical workflow which included ultra-performance hydrophilic interaction liquid chromatography with fluorescence detection (UPLC-HILIC-FLD) and coupling to a quadrupole time of flight (qTOF) mass spectrometer (MS), detailed oligosaccharide libraries were established. The partial or full characterization of the neutral/fucosylated, phosphorylated and sialylated structures was facilitated by sequencing with linkage- and sugar- specific exoglycosidases. Relative peak quantification of the 2-AB labelled oligosaccharides provided additional information. Milks from domestic animals contained a much larger variety of complex oligosaccharides than was previously assumed and thirteen of these structures were previously identified in human milk. The direct comparison of the oligosaccharide mixtures could contribute to a better understanding of possible differences in their biological effects and highlight the potential value of animal milks for commercial oligosaccharide extraction.Fil: Albrecht, Simone. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; IrlandaFil: Lane, Jonathan A.. Teagasc Food Research Centre; IrlandaFil: Mariño, Karina Valeria. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Al Busadah, Khalid A.. King Faisal University. Camel Research Center; Arabia SauditaFil: Carrington, Stephen D.. University College Dublin. Veterinary Sciences Centre; IrlandaFil: Hickey, Rita M.. Teagasc Food Research Centre; IrlandaFil: Rudd, Pauline M.. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; Irland

Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda

Background Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. Methods and findings This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure \u3c140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p \u3c 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. Conclusions In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA

Synthesis of global satellite observations of magmatic and volcanic deformation: implications for volcano monitoring & the lateral extent of magmatic domains

Global Synthetic Aperture Radar (SAR) measurements made over the past decades provide insights into the lateral extent of magmatic domains, and capture volcanic process on scales useful for volcano monitoring. Satellite-based SAR imagery has great potential for monitoring topographic change, the distribution of eruptive products and surface displacements (InSAR) at subaerial volcanoes. However, there are challenges in applying it routinely, as would be required for the reliable operational assessment of hazard. The deformation detectable depends upon satellite repeat time and swath widths, relative to the spatial and temporal scales of volcanological processes. We describe the characteristics of InSAR-measured volcano deformation over the past two decades, highlighting both the technique’s capabilities and its limitations as a monitoring tool. To achieve this, we draw on two global datasets of volcano deformation: the Smithsonian Institution Volcanoes of the World database and the Centre for the Observation and Modelling of Earthquakes, Volcanoes and Tectonics volcano deformation catalogue, as well as compiling some measurement characteristics and interpretations from the primary literature. We find that a higher proportion of InSAR observations capture non-eruptive and non-magmatic processes than those from ground-based instrument networks, and that both transient ( 5 years) deformation episodes are under-represented. However, satellite radar is already used to assess the development of extended periods of unrest and long-lasting eruptions, and improved spatial resolution and coverage have resulted in the detection of previously unrecognised deformation at both ends of the spatial scale (~ 10 to > 1000 km²). ‘Baseline’ records of past InSAR measurements, including ‘null’ results, are fundamental for any future interpretation of interferograms in terms of hazard‚ both by providing information about past deformation at an individual volcano, and for assessing the characteristics of deformation that are likely to be detectable (and undetectable) using InSAR. More than half of all InSAR deformation signals attributed to magmatic processes have sources in the shallow crust (< 5 km depth). While the depth distribution of InSAR-derived deformation sources is affected by measurement limitations, their lateral distribution provides information about the extent of active magmatic domains. Deformation is common (24% of all potentially magmatic events) at loci ≥5 km away from the nearest active volcanic vent. This demonstrates that laterally extensive active magmatic domains are not exceptional, but can comprise the shallowest part of trans-crustal magmatic systems in a range of volcanic settings

Potential of a cyclone prototype spacer to improve in vitro dry powder delivery

Copyright The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedPurpose: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrierbased DPIs was investigated. Methods: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30-60 Lmin-1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Results: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51 % at 30 Lmin-1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. Conclusion: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.Peer reviewe