Response to the Letter to the Editor by Eberhard et al.

In a Letter to the Editor, Eberhard et al. question the validity of our model of skin snip sensitivity and argue against the use of skin snips to evaluate onchocerciasis elimination by mass drug administration. Here we discuss their arguments and compare model predictions with observed data to assess the validity of our model

Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings.

BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. METHODS: We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. RESULTS: The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment. CONCLUSIONS: Our model supports the timelines proposed by APOC for post-MDA follow-up and surveillance surveys every 3-5 years. Two skin snips from the iliac region have reasonable sensitivity to detect residual infection, but the sensitivity can be significantly improved by taking 4 snips. The costs and benefits of using four versus two snips should be evaluated

What Predicts Hospital Admissions in Community-Dwelling People With Parkinsonism?

Objectives: Previous studies have looked at the reasons for hospital admission in people with parkinsonism (PwP), yet few have looked at factors that precipitate admission. Methods: People with parkinsonism with a diagnosis of idiopathic Parkinson disease of Hoehn and Yahr stage III-V and those with Parkinson plus syndromes were assessed for motor and nonmotor symptoms, quality of life, and functional performance. Logistic regression was used to investigate predictors of hospital admission over the subsequent 2 years. Results: Overall, 162 patients consented to be part of the study. Seventy-one PwP (43.8%) had at least 1 hospital admission, and 17 (10.5%) patients had 3 or more admissions to hospital. Poorer cognition, more nonmotor symptoms, poorer quality of life, slower timed-up-and-go test scores, and abnormal swallow predicted a subsequent hospital admission. Discussion: Our study emphasizes the importance of nonmotor symptoms in predicting admission. A cost–benefit analysis of early intervention to prevent admission should be considered

Understanding Caregiver Strain in Parkinsonism—A Mixed Methods Approach

Background: Parkinsonism, including Parkinson’s disease (PD) are progressive neurological conditions. As these condition progress, individuals will need more support with their care needs to maintain independent community-living. Care needs are mainly met by unpaid, informal caregivers, usually close family members or friends. Caregiver strain is thought to lead to the need for care home placement when the caregiver can no longer cope. Objective: To understand predictors of caregiver strain and its influence on care home placement for people with moderate to advanced Parkinsonism. Methods: This is a convergent mixed methods study. Quantitative data, following an adapted stress-appraisal model, were collected on caregiver profile, tasks performed and causes of caregiver strain. Semi-structured, in-depth interviews were conducted with caregivers of people with PD (PwP) who went into a care home during the study period, to develop a deeper understanding of the caregiver role and the factors influencing caregiver strain. Results: Quantitative data were collected from 115 patient caregiver dyads. Interviews were conducted with 10 caregivers. A model to predict caregiver strain was developed and predictors of caregiver strain were identified, such as functional disability and poor caregiver sleep. Conclusion: Our findings further demonstrate the complexity of carer strain. Particular dimensions are identified that need to be addressed within clinical practice to reduce carer strain and support people with Parkinsonism to remain within their own home for as long as possible

Directly Measured Heating Rates of a Tropical Subvisible Cirrus Cloud

We present the first direct measurements of the infrared and solar heating rates of a tropical subvisible cirrus (SVC) cloud sampled off the east coast of Nicaragua on 25 July 2007 by the NASA ER-2 aircraft during the Tropical Composition, Cloud and Climate Coupling Experiment (TC4). On this day a persistent thin cirrus layer, with mostly clear skies underneath, was detected in real time by the cloud lidar on the ER-2, and the aircraft was directed to profile down through the SVC. Measurements of the net broadband infrared irradiance and spectrally integrated solar irradiance above, below, and through the SVC are used to determine the infrared and solar heating rates of the cloud. The lidar measurements show that the variable SVC layer was located between approximately 13 and 15 km. Its midvisible optical depth varied from 0.01 to 0.10 with a mean of 0.034 +/- 0.033. Its depolarization ratio was approximately 0.4, indicative of ice clouds. From the divergence of the measured net irradiances the infrared heating rate of the SVC was determined to be approximately 2.50 - 3.24 K/d and the solar heating rate was found to be negligible. These values are consistent with previous indirect observations of other SVC and with model-generated heating rates of SVC with similar optical depths. This study illustrates the utility and potential of the profiling sampling strategy employed here. A more fully instrumented high-altitude aircraft that also included in situ cloud and aerosol probes would provide a comprehensive data set for characterizing both the radiative and microphysical properties of these ubiquitous tropical cloud

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

Developmental changes in the critical information used for facial expression processing

Facial expression recognition skills are known to improve across childhood and adolescence, but the mechanisms driving the development of these important social abilities remain unclear. This study investigates directly whether there are qualitative differences in child and adult processing strategies for these emotional stimuli. With a novel adaptation of the Bubbles reverse-correlation paradigm (Gosselin & Schyns, 2001), we added noise to expressive face stimuli and presented sub-sets of randomly sampled information from each image at different locations and spatial frequency bands across experimental trials. Results from our large developmental sample: 71 young children (6 -9 years), 69 older children (10-13 years) and 54 adults, uniquely reveal flexible profiles of strategic information-use for categorisations of fear, sadness, happiness and anger at all ages. All three groups relied upon a distinct set of key facial features for each of these expressions, with fine-tuning of this diagnostic information (features and spatial frequency) observed across developmental time. Reported variability in the developmental trajectories for different emotional expressions is consistent with the notion of functional links between the refinement of information-use and processing ability

Efficacy of a training intervention on the quality of practitioners' decision support for patients deciding about place of care at the end of life: A randomized control trial: Study protocol

<p>Abstract</p> <p>Background</p> <p>Most people prefer home palliation but die in an institution. Some experience decisional conflict when weighing options regarding place of care. Clinicians can identify patients' decisional needs and provide decision support, yet generally lack skills and confidence in doing so. This study aims to determine whether the quality of clinicians' decision support can be improved with a brief, theory-based, skills-building intervention.</p> <p>Theory</p> <p>The Ottawa Decision Support Framework (ODSF) guides an evidence based, practical approach to assist clinicians in providing high-quality decision support. The ODSF proposes that decisional needs [personal uncertainty, knowledge, values clarity, support, personal characteristics] strongly influence the quality of decisions patients make. Clinicians can improve decision quality by providing decision support to address decisional needs [clarify decisional needs, provide facts and probabilities, clarify values, support/guide deliberation, monitor/facilitate progress].</p> <p>Methods/Design</p> <p>The efficacy of a brief education intervention will be assessed in a two-phase study. In phase one a focused needs assessment will be conducted with key informants. Phase two is a randomized control trial where clinicians will be randomly allocated to an intervention or control group. The intervention, informed by the needs assessment, knowledge transfer best practices and the ODSF, comprises an online tutorial; an interactive skills building workshop; a decision support protocol; performance feedback, and educational outreach. Participants will be assessed: a) at baseline (quality of decision support); b) after the tutorial (knowledge); and c) four weeks after the other interventions (quality of decision support, intention to incorporate decision support into practice and perceived usefulness of intervention components). Between group differences in the primary outcome (quality of decision support scores) will be analyzed using ANOVA.</p> <p>Discussion</p> <p>Few studies have investigated the efficacy of an evidence-based, theory guided intervention aimed at assisting clinicians to strengthen their patient decision support skills. Expanding our understanding of how clinicians can best support palliative patients' decision-making will help to inform best practices in patient-centered palliative care. There is potential transferability of lessons learned to other care situations such as chronic condition management, advance directives and anticipatory care planning. Should the efficacy evaluation reveal clear improvements in the quality of decision support provided by clinicians who received the intervention, a larger scale implementation and effectiveness trial will be considered.</p> <p>Trial registration</p> <p>This study is registered as NCT00614003</p

Mixed-species plantations of eucalyptus with nitrogen fixing trees: a review

Mixed-species plantations of Eucalyptus with a nitrogen (N2) fixing species have the potential to increase productivity while maintaining soil fertility, compared to Eucalyptus monocultures. However, it is difficult to predict combinations of species and sites that will lead to these benefits. We review the processes and interactions occurring in mixed plantations, 5 and the influence of species or site attributes, to aid the selection of successful combinations of species and sites. Successful mixtures, where productivity is increased over that of monocultures, have often developed stratified canopies, such that the less shade-tolerant species overtops the more shadetolerant species. Successful mixtures also have significantly higher rates of N and P cycling than 10 Eucalyptus monocultures. It is therefore important to select N2-fixing species with readily decomposable litter and high rates of nutrient cycling, as well as high rates of N2-fixation. While the dynamics of N2-fixation in tree stands are not well understood, it appears as though eucalypts can benefit from fixed N as early as the first or second year following plantation establishment. A meta-analysis of 18 published studies revealed several trials in which mixtures were significantly 15 (