Characterization of a broad-based mosquito yeast interfering RNA larvicide with a conserved target site in mosquito semaphorin-1a genes

BACKGROUND: RNA interference (RNAi), which has facilitated functional characterization of mosquito neural development genes such as the axon guidance regulator semaphorin-1a (sema1a), could one day be applied as a new means of vector control. Saccharomyces cerevisiae (baker's yeast) may represent an effective interfering RNA expression system that could be used directly for delivery of RNA pesticides to mosquito larvae. Here we describe characterization of a yeast larvicide developed through bioengineering of S. cerevisiae to express a short hairpin RNA (shRNA) targeting a conserved site in mosquito sema1a genes. RESULTS: Experiments conducted on Aedes aegypti larvae demonstrated that the yeast larvicide effectively silences sema1a expression, generates severe neural defects, and induces high levels of larval mortality in laboratory, simulated-field, and semi-field experiments. The larvicide was also found to induce high levels of Aedes albopictus, Anopheles gambiae and Culex quinquefasciatus mortality. CONCLUSIONS: The results of these studies indicate that use of yeast interfering RNA larvicides targeting mosquito sema1a genes may represent a new biorational tool for mosquito control

A Primary Care Nurse-Delivered Walking Intervention in Older Adults: PACE (Pedometer Accelerometer Consultation Evaluation)-Lift Cluster Randomised Controlled Trial.

Background: Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA. Methods and Findings: A total of 988 60–75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention’s acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group: by 1,037 (95% CI 513–1,560) steps/day and 63 (95% CI 40–87) minutes/week, respectively. At 12 months corresponding differences were 609 (95% CI 104–1,115) steps/day and 40 (95% CI 17–63) minutes/week. Counts and counts/minute showed similar effects to steps and MVPA. Adverse events, anthropometry, mood, and pain were similar in the two groups. Participants and practice nurses found the intervention acceptable and enjoyable. Conclusions : The PACE-Lift trial increased both step-counts and objectively measured MVPA in ≥10-minute bouts in 60–75 year olds at 3 and 12 months, with no effect on adverse events. To our knowledge, this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting. Trial Registration: Controlled-Trials.com ISRCTN4212256

Experimental tree removal in tallgrass prairie: Variable responses of flora and fauna along a woody cover gradient

Woody plant encroachment is a worldwide phenomenon in grassland and savanna systems whose consequence is often the development of an alternate woodland state. Theoretically, an alternate state may be associated with changes in system state variables (e.g., species composition) or abiotic parameter shifts (e.g., nutrient availability). When state-variable changes are cumulative, such as in woody plant encroachment, the probability of parameter shifts increases as system feedbacks intensify over time. Using a Before-After Control-Impact (BACI) design, we studied eight pairs of grassland sites undergoing various levels of eastern redcedar (Juniperus virginiana) encroachment to determine whether responses of flora and fauna to experimental redcedar removal differed according to the level of pretreatment redcedar cover. In the first year after removal, herbaceous plant species diversity and evenness, woody plant evenness, and invertebrate family richness increased linearly with pretreatment redcedar cover, whereas increases in small-mammal diversity and evenness were described by logarithmic trends. In contrast, increases in woody plant diversity and total biomass of terrestrial invertebrates were accentuated at levels of higher pretreatment cover. Tree removal also shifted small-mammal species composition toward a more grassland-associated assemblage. During the second year postremoval, increases in herbaceous plant diversity followed a polynomial trend, but increases in most other metrics did not vary along the pretreatment cover gradient. These changes were accompanied by extremely high growing-season precipitation, which may have homogenized floral and faunal responses to removal. Our results demonstrate that tree removal increases important community metrics among grassland flora and fauna within two years, with some responses to removal being strongly influenced by the stage of initial encroachment and modulated by climatic variability. Our results underscore the importance of decisive management for reversing the effects of woody plant encroachment in imperiled grassland ecosystems.Peer reviewedNatural Resource Ecology and Managemen

Burning in the growing season

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PACE-UP (Pedometer and consultation evaluation--UP)--a pedometer-based walking intervention with and without practice nurse support in primary care patients aged 45-75 years: study protocol for a randomised controlled trial.

BACKGROUND: Most adults do not achieve the 150 minutes weekly of at least moderate intensity activity recommended for health. Adults' most common physical activity (PA) is walking, light intensity if strolling, moderate if brisker. Pedometers can increase walking; however, most trials have been short-term, have combined pedometer and support effects, and have not reported PA intensity. This trial will investigate whether pedometers, with or without nurse support, can help less active 45-75 year olds to increase their PA over 12 months. METHODS/DESIGN: DESIGN: Primary care-based 3-arm randomized controlled trial with 12-month follow-up and health economic and qualitative evaluations. PARTICIPANTS: Less active 45-75 year olds (n = 993) will be recruited by post from six South West London general practices, maximum of two per household and households randomised into three groups. Step-count and time spent at different PA intensities will be assessed for 7 days at baseline, 3 and 12 months by accelerometer. Questionnaires and anthropometric assessments will be completed. INTERVENTION: The pedometer-alone group will be posted a pedometer (Yamax Digi-Walker SW-200), handbook and diary detailing a 12-week pedometer-based walking programme, using targets from their baseline assessment. The pedometer-plus-support group will additionally receive three practice nurse PA consultations. The handbook, diary and consultations include behaviour change techniques (e.g., self-monitoring, goal-setting, relapse prevention planning). The control group will receive usual care. OUTCOMES: Changes in average daily step-count (primary outcome), time spent sedentary and in at least moderate intensity PA weekly at 12 months, measured by accelerometry. Other outcomes include change in body mass index, body fat, self-reported PA, quality of life, mood and adverse events. Cost-effectiveness will be assessed by the incremental cost of the intervention to the National Health Service and incremental cost per change in step-count and per quality adjusted life year. Qualitative evaluations will explore reasons for trial non-participation and the interventions' acceptability. DISCUSSION: The PACE-UP trial will determine the effectiveness and cost-effectiveness of a pedometer-based walking intervention delivered by post or practice nurse to less active primary care patients aged 45-75 years old. Approaches to minimise bias and challenges anticipated in delivery will be discussed

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

Hospital length of stay and surgery among European children with rare structural congenital anomalies – A population-based data linkage study

Little is known about morbidity for children with rare structural congenital anomalies. This European, population-based data-linkage cohort study analysed data on hospitalisations and surgical procedures for 5948 children born 1995-2014 with 18 rare structural congenital anomalies from nine EUROCAT registries in five countries. In the first year of life, the median length of stay (LOS) ranged from 3.5 days (anotia) to 53.8 days (atresia of bile ducts). Generally, children with gastrointestinal anomalies, bladder anomalies and Prune-Belly had the longest LOS. At ages 1-4, the median LOS per year was ≤3 days for most anomalies. The proportion of children having surgery before age 5 years ranged from 40% to 100%. The median number of surgical procedures for those under 5 years was two or more for 14 of the 18 anomalies and the highest for children with Prune-Belly at 7.4 (95% CI 2.5-12.3). The median age at first surgery for children with atresia of bile ducts was 8.4 weeks (95% CI 7.6-9.2) which is older than international recommendations. Results from the subset of registries with data up to 10 years of age showed that the need for hospitalisations and surgery continued. The burden of disease in early childhood is high for children with rare structural congenital anomalies

iSAW: Integrating Structure, Actors, and Water to Study Socio-Hydro-Ecological Systems

Urbanization, climate, and ecosystem change represent major challenges for managing water resources. Although water systems are complex, a need exists for a generalized representation of these systems to identify important components and linkages to guide scientific inquiry and aid water management. We developed an integrated Structure-Actor-Water framework (iSAW) to facilitate the understanding of and transitions to sustainable water systems. Our goal was to produce an interdisciplinary framework for water resources research that could address management challenges across scales (e.g., plot to region) and domains (e.g., water supply and quality, transitioning, and urban landscapes). The framework was designed to be generalizable across all human–environment systems, yet with sufficient detail and flexibility to be customized to specific cases. iSAW includes three major components: structure (natural, built, and social), actors (individual and organizational), and water (quality and quantity). Key linkages among these components include: (1) ecological/hydrologic processes, (2) ecosystem/geomorphic feedbacks, (3) planning, design, and policy, (4) perceptions, information, and experience, (5) resource access and risk, and (6) operational water use and management. We illustrate the flexibility and utility of the iSAW framework by applying it to two research and management problems: understanding urban water supply and demand in a changing climate and expanding use of green storm water infrastructure in a semi-arid environment. The applications demonstrate that a generalized conceptual model can identify important components and linkages in complex and diverse water systems and facilitate communication about those systems among researchers from diverse disciplines

Assessment of Trinidad community stakeholder perspectives on the use of yeast interfering RNA-baited ovitraps for biorational control of Aedes mosquitoes

Dengue, Zika, chikungunya and yellow fever viruses continue to be a major public health burden. Aedes mosquitoes, the primary vectors responsible for transmitting these viral pathogens, continue to flourish due to local challenges in vector control management. Yeast interfering RNA-baited larval lethal ovitraps are being developed as a novel biorational control tool for Aedes mosquitoes. This intervention circumvents increasing issues with insecticide resistance and poses no known threat to non-target organisms. In an effort to create public awareness of this alternative vector control strategy, gain stakeholder feedback regarding product design and acceptance of the new intervention, and build capacity for its potential integration into existing mosquito control programs, this investigation pursued community stakeholder engagement activities, which were undertaken in Trinidad and Tobago. Three forms of assessment, including paper surveys, community forums, and household interviews, were used with the goal of evaluating local community stakeholders' knowledge of mosquitoes, vector control practices, and perceptions of the new technology. These activities facilitated evaluation of the hypothesis that the ovitraps would be broadly accepted by community stakeholders as a means of biorational control for Aedes mosquitoes. A comparison of the types of stakeholder input communicated through use of the three assessment tools highlighted the utility and merit of using each tool for assessing new global health interventions. Most study participants reported a general willingness to purchase an ovitrap on condition that it would be affordable and safe for human health and the environment. Stakeholders provided valuable input on product design, distribution, and operation. A need for educational campaigns that provide a mechanism for educating stakeholders about vector ecology and management was highlighted. The results of the investigation, which are likely applicable to many other Caribbean nations and other countries with heavy arboviral disease burdens, were supportive of supplementation of existing vector control strategies through the use of the yeast RNAi-based ovitraps

Hospital care in the first ten years of life of children with congenital anomalies in six European countries: Data from the EUROlinkCAT Cohort linkage study

Objective To quantify the hospital care for children born with a major congenital anomaly up to 10 years of age compared with children without a congenital anomaly.Design, setting and patients 79 591 children with congenital anomalies and 2 021 772 children without congenital anomalies born 1995–2014 in six European countries in seven regions covered by congenital anomaly registries were linked to inpatient electronic health records up to their 10th birthday.Main outcome measures Number of days in hospital and number of surgeries.Results During the first year of life among the seven regions, a median of 2.4% (IQR: 2.3, 3.2) of children with a congenital anomaly accounted for 18% (14, 24) of days in hospital and 63% (62, 76) of surgeries. Over the first 10 years of life, the percentages were 17% (15, 20) of days in hospital and 20% (19, 22) of surgeries. Children with congenital anomalies spent 8.8 (7.5, 9.9) times longer in hospital during their first year of life than children without anomalies (18 days compared with 2 days) and 5 (4.1–6.1) times longer aged, 5–9 (0.5 vs 0.1 days). In the first year of life, children with gastrointestinal anomalies spent 40 times longer and those with severe heart anomalies 20 times longer in hospital reducing to over 5 times longer when aged 5–9.Conclusions Children with a congenital anomaly consume a significant proportion of hospital care resources. Priority should be given to public health primary prevention measures to reduce the risk of congenital anomalies