Co-morbidity burden in Parkinson’s disease : Comparison with controls and its influence on prognosis

Financial support This study was funded by Parkinson’s UK, the Scottish Chief Scientist Office, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING. The funders had no involvement in the study. Acknowledgements We acknowledge funding for the PINE study from Parkinson’s UK (G-0502, G-0914, G-1302), the Scottish Chief Scientist Office(CAF/12/05), the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, NHS Grampian endowments and SPRING. We thank the patients and controls for their participation and the research staff who collected data and supported the study database.Peer reviewedPostprintPostprintPublisher PD

Evaluating uncertainty in estimates of soil moisture memory with a reverse ensemble approach

Soil moisture memory is a key component of seasonal predictability. However, uncertainty in current memory estimates is not clear and it is not obvious to what extent these are dependent on model uncertainties. To address this question, we perform a global sensitivity analysis of memory to key hydraulic parameters, using an uncoupled version of the H-TESSEL land surface model. Results show significant dependency of estimates of memory and its uncertainty on these parameters, suggesting that operational seasonal forecasting models using deterministic hydraulic parameter values are likely to display a narrower range of memory than exists in reality. Explicitly incorporating hydraulic parameter uncertainty into models may then give improvements in forecast skill and reliability, as has been shown elsewhere in the literature. Our results also show significant differences with previous estimates of memory uncertainty, warning against placing too much confidence in a single quantification of uncertainty

Population need for primary eye care in Rwanda: A national survey.

BACKGROUND: Universal access to Primary Eye Care (PEC) is a key global initiative to reduce and prevent avoidable causes of visual impairment (VI). PEC can address minor eye conditions, simple forms of uncorrected refractive error (URE) and create a referral pathway for specialist eye care, thus offering a potential solution to a lack of eye health specialists in low-income countries. However, there is little information on the population need for PEC, including prevalence of URE in all ages in Sub-Saharan Africa. METHODS: A national survey was conducted of people aged 7 and over in Rwanda in September-December 2016. Participants were selected through two-stage probability proportional to size sampling and compact segment sampling. VI (visual acuity<6/12) was assessed using Portable Eye Examination Kit (PEEK); URE was detected using a pinhole and presbyopia using local near vision test. We also used validated questionnaires to collect socio-demographic and minor eye symptoms information. Prevalence estimates for VI, URE and need for PEC (URE, presbyopia with good distance vision, need for referrals and minor eye conditions) were age and sex standardized to the Rwandan population. Associations between age, sex, socio-economic status and the key outcomes were examined using logistic regression. RESULTS: 4618 participants were examined and interviewed out of 5361 enumerated (86% response rate). The adjusted population prevalence of VI was 3.7% (95%CI = 3.0-4.5%), URE was 2.2% (95%CI = 1.7-2.8%) and overall need for PEC was 34.0% (95%CI = 31.8-36.4%). Women and older people were more likely to need PEC and require a referral. CONCLUSIONS: Nearly a third of the population in Rwanda has the potential to benefit from PEC, with greater need identified in older people and women. Universal access to PEC can address unmet eye health needs and public health planning needs to ensure equitable access to older people and women

Cadherin-26 (CDH26) regulates airway epithelial cell cytoskeletal structure and polarity.

Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell-cell contact and cell integrity through maintaining cytoskeletal structures. Overexpression of CDH26 in cells with a fibroblastoid phenotype increases contact inhibition and promotes monolayer formation and cortical actin structures. CDH26 expression is also important for localization of planar cell polarity proteins. Knockdown of CDH26 in AECs results in loss of cortical actin and disruption of CRB3 and other proteins associated with apical polarity. Together, our findings uncover previously unrecognized functions for CDH26 in the maintenance of actin cytoskeleton and apicobasal polarity of AECs

Larval Diet Abundance Influences Size and Composition of the Midgut Microbiota of Aedes aegypti Mosquitoes

The midgut microbiota of the yellow fever mosquito Aedes aegypti impacts pathogen susceptibility and transmission by this important vector species. However, factors influencing the composition and size of the microbiome in mosquitoes are poorly understood. We investigated the impact of larval diet abundance during development on the composition and size of the larval and adult microbiota by rearing Aedes aegypti under four larval food regimens, ranging from nutrient deprivation to nutrient excess. We assessed the persistent impacts of larval diet availability on the microbiota of the larval breeding water, larval mosquitoes, and adult mosquitoes under sugar and blood fed conditions using qPCR and high-throughput 16S amplicon sequencing to determine bacterial load and microbiota composition. Bacterial loads in breeding water increased with increasing larval diet. Larvae reared with the lowest diet abundance had significantly fewer bacteria than larvae from two higher diet treatments, but not from the highest diet abundance. Adults from the lowest diet abundance treatment had significantly fewer bacteria in their midguts compared to all higher diet abundance treatments. Larval diet amount also had a significant impact on microbiota composition, primarily within larval breeding water and larvae. Increasing diet correlated with increased relative levels of Enterobacteriaceae and Flavobacteriaceae and decreased relative levels of Sphingomonadaceae. Multiple individual OTUs were significantly impacted by diet including one mapping to the genus Cedecea, which increased with higher diet amounts. This was consistent across all sample types, including sugar fed and blood fed adults. Taken together, these data suggest that availability of diet during development can cause lasting shifts in the size and composition of the microbiota in the disease vector Aedes aegypti

Impact of Hearing Aids on Poverty, Quality of Life and Mental Health in Guatemala: Results of a before and after Study.

There are 466 million people globally with disabling hearing loss, many of whom can benefit from hearing aids. The aim of the study was to assess the impact of providing hearing aids on poverty, mental health, quality of life, and activities, among adults in Guatemala. A nonrandomised before and after study was conducted, with a comparison group to assess for secular trends. Adult cases with bilateral hearing impairment were identified within 150 km of Guatemala City, as well as age- and sex-matched comparison subjects without disabling hearing loss. All participants were interviewed with a semistructured questionnaire, and cases were offered hearing aids. Participants were reinterviewed 6-9 months later. We interviewed 135 cases and 89 comparison subjects at baseline and follow-up. At baseline, cases were poorer than comparison subjects with respect to individual income (p = 0.01), household income (p = 0.02), and per capita expenditure (PCE) (p = 0.003). After provision of hearing aids, median household income improved among cases (p = 0.03). In the comparison group, median individual income (p = 0.01) and PCE (p = 0.03) fell between baseline at follow-up. At follow-up, there were also improvements in productive time use, quality of life, and depressive symptoms among cases, but these were less apparent in the comparison group. In conclusion, this study has demonstrated a positive effect of hearing aids in improving quality of life, economic circumstances and mental health among Guatemalan adults

Six-Year Incidence of Blindness and Visual Impairment in Kenya: The Nakuru Eye Disease Cohort Study.

PURPOSE: To describe the cumulative 6-year incidence of visual impairment (VI) and blindness in an adult Kenyan population. The Nakuru Posterior Segment Eye Disease Study is a population-based sample of 4414 participants aged ?50 years, enrolled in 2007-2008. Of these, 2170 (50%) were reexamined in 2013-2014. METHODS: The World Health Organization (WHO) and US definitions were used to calculate presenting visual acuity classifications based on logMAR visual acuity tests at baseline and follow-up. Detailed ophthalmic and anthropometric examinations as well as a questionnaire, which included past medical and ophthalmic history, were used to assess risk factors for study participation and vision loss. Cumulative incidence of VI and blindness, and factors associated with these outcomes, were estimated. Inverse probability weighting was used to adjust for nonparticipation. RESULTS: Visual acuity measurements were available for 2164 (99.7%) participants. Using WHO definitions, the 6-year cumulative incidence of VI was 11.9% (95%CI [confidence interval]: 10.3-13.8%) and blindness was 1.51% (95%CI: 1.0-2.2%); using the US classification, the cumulative incidence of blindness was 2.70% (95%CI: 1.8-3.2%). Incidence of VI increased strongly with older age, and independently with being diabetic. There are an estimated 21 new cases of VI per year in people aged ?50 years per 1000 people, of whom 3 are blind. Therefore in Kenya we estimate that there are 92,000 new cases of VI in people aged ?50 years per year, of whom 11,600 are blind, out of a total population of approximately 4.3 million people aged 50 and above. CONCLUSIONS: The incidence of VI and blindness in this older Kenyan population was considerably higher than in comparable studies worldwide. A continued effort to strengthen the eye health system is necessary to support the growing unmet need in an aging and growing population