Functional characterization of a glutamate/aspartate transporter from the mosquito Aedes aegypti

Glutamate elicits a variety of effects in insects, including inhibitory and excitatory signals at both neuromuscular junctions and brain. Insect glutamatergic neurotransmission has been studied in great depth especially from the standpoint of the receptor-mediated effects, but the molecular mechanisms involved in the termination of the numerous glutamatergic signals have only recently begun to receive attention. In vertebrates, glutamatergic signals are terminated by Na^+/K^+-dependent high-affinity excitatory amino acid transporters (EAAT), which have been cloned and characterized extensively. Cloning and characterization of a few insect homologues have followed, but functional information for these homologues is still limited. Here we report a study conducted on a cloned mosquito EAAT homologue isolated from the vector of the dengue virus, Aedes aegypti. The deduced amino acid sequence of the protein, AeaEAAT, exhibits 40–50% identity with mammalian EAATs, and 45–50% identity to other insect EAATs characterized thus far. It transports l-glutamate as well as l- and d-aspartate with high affinity in the micromolar range, and demonstrates a substrate-elicited anion conductance when heterologously expressed in Xenopus laevis oocytes, as found with mammalian homologues. Analysis of the spatial distribution of the protein demonstrates high expression levels in the adult thorax, which is mostly observed in the thoracic ganglia. Together, the work presented here provides a thorough examination of the role played by glutamate transport in Ae. aegypti

The transporter-like protein inebriated mediates hyperosmotic stimuli through intracellular signaling

We cloned the inebriated homologue MasIne from Manduca sexta and expressed it in Xenopus laevis oocytes. MasIne is homologous to neurotransmitter transporters but no transport was observed with a number of putative substrates. Oocytes expressing MasIne respond to hyperosmotic stimulation by releasing intracellular Ca(2+), as revealed by activation of the endogenous Ca(2+)-activated Cl(-) current. This Ca(2+) release requires the N-terminal 108 amino acid residues of MasIne and occurs via the inositol trisphosphate pathway. Fusion of the N terminus to the rat gamma-aminobutyric acid transporter (rGAT1) also renders rGAT1 responsive to hyperosmotic stimulation. Immunohistochemical analyses show that MasIne and Drosophila Ine have similar tissue distribution patterns, suggesting functional identity. Inebriated is expressed in tissues and cells actively involved in K(+) transport, which suggests that it may have a role in ion transport, particularly of K(+). We propose that stimulation of MasIne releases intracellular Ca(2+) in native tissues, activating Ca(2+)-dependent K(+) channels, and leading to K(+) transport

Physician and Other Healthcare Personnel Responses to Hospital Stroke Quality of Care Performance Feedback: A Qualitative Study

Background Understanding how physicians and other healthcare personnel respond to hospital performance feedback initiatives may have important implications for quality improvement efforts. Our objective was to explore responses to the inaugural feedback of hospital performance on stroke quality of care measures among relevant physicians and personnel at the US Department of Veterans Health Administration (VHA) hospitals. Methods Qualitative interviews with hospital administrators, physicians, nurses and quality managers at 12 VHA hospitals in the USA after the inaugural national release of the report on quality of acute stroke care processes. Interview transcripts were analysed using an immersion/crystallisation approach to identify recurrent themes. Results Interviews were completed with 41 individuals at 12 VHA hospitals from diverse regions of the USA; the majority were clinicians, either physicians or nurses, and nearly all had 20 years of experience or more. Interviewees described general perceptions of internal performance feedback that were both positive and negative, such as the notion that performance feedback could provide value to clinicians and hospitals, but at the same time voiced concerns about being inundated with such data. Interviewees also expressed scepticism about public reporting of performance data, citing numerous concerns and limitations. However, when interviewees described specific experiences with performance feedback, nearly all reactions were positive, including excitement, interest and feeling validated about a job well done. Discussion Physicians and other healthcare personnel described hospital performance feedback on stroke quality of care measures to be broadly valuable but identified areas of concern related to the measurement process and public reporting

Optimal control for halo orbit missions

This paper addresses the computation of the required trajectory correction maneuvers (TCM) for a halo orbit space mission to compensate for the launch velocity errors introduced by inaccuracies of the launch vehicle. By combiningdynamical systems theory with optimal control techniques, we produce a portrait of the complex landscape of the trajectory design space. This approach enables parametric studies not available to mission designers a few years ago, such as how the magnitude of the errors and the timingof the first TCM affect the correction ΔV. The impetus for combiningdynamical systems theory and optimal control in this problem arises from design issues for the Genesis Discovery mission being developed for NASA by the Jet Propulsion Laboratory

Halo orbit mission correction maneuvers using optimal control

This paper addresses the computation of the required trajectory correction maneuvers for a halo orbit space mission to compensate for the launch velocity errors introduced by inaccuracies of the launch vehicle. By combining dynamical systems theory with optimal control techniques, we are able to provide a compelling portrait of the complex landscape of the trajectory design space. This approach enables automation of the analysis to perform parametric studies that simply were not available to mission designers a few years ago, such as how the magnitude of the errors and the timing of the first trajectory correction maneuver affects the correction ΔV. The impetus for combining dynamical systems theory and optimal control in this problem arises from design issues for the Genesis Discovery Mission being developed for NASA by the Jet Propulsion Laboratory

Estimating the Magnitude of Illicit Cigarette Trade in Bangladesh:Protocol for a Mixed-Methods Study

The illicit tobacco trade undermines the effectiveness of tobacco tax policies; increases the availability of cheap cigarettes, which, in turn, increases tobacco use and tobacco related deaths; and causes huge revenue losses to governments. There is limited evidence on the extent of illicit tobacco trade particularly cigarettes in Bangladesh. The paper presents the protocol for a mixed-methods study to estimate the extent of illicit cigarette trade in Bangladesh. The study will address three research questions: (a) What proportion of cigarettes sold as retail are illicit? (b) What are the common types of tax avoidance and tax evasion? (c) Can pack examination from the trash recycle market be considered as a new method to assess illicit trade in comparison to that from retailers and streets? Following an observational research method, data will be collected utilizing empty cigarette packs from three sources: (a) retailers; (b) streets; and (c) trash recycle market. In addition, a structured questionnaire will be used to collect information from retailers selling cigarettes. We will select post codes as Primary Sampling Unit (PSU) using a multi-stage random sampling technique. We will randomly select eight districts from eight divisions stratified by those with land border and non-land border; and within each district, we will randomly select ten postcodes, stratified by rural (five) and urban (five) PSU to ensure maximum geographical variation, leading to a total of eighty post codes from eight districts. The analysis will report the proportions of packs that do not comply with the study definition of illicit. Independent estimates of illicit tobacco are rare in low-and middle-income countries such as Bangladesh. Findings will inform efforts by revenue authorities and others to address the effects of illicit trade and counter tobacco industry claims

Correlation of inpatient and outpatient measures of stroke care quality within veterans health administration hospitals

Background and Purpose—Quality of care delivered in the inpatient and ambulatory settings may be correlated within an integrated health system such as the Veterans Health Administration. We examined the correlation between stroke care quality at hospital discharge and within 6 months postdischarge. Methods—We conducted a cross-sectional hospital-level correlation analyses of chart-abstracted data for 3467 veterans discharged alive after an acute ischemic stroke from 108 Veterans Health Administration medical centers and 2380 veterans with postdischarge follow-up within 6 months in fiscal year 2007. Four risk-standardized processes of care represented discharge care quality: prescription of antithrombotic and antilipidmic therapy, anticoagulation for atrial fibrillation, and tobacco cessation counseling along with a composite measure of defect-free care. Five risk-standardized intermediate outcomes represented postdischarge care quality: achievement of blood pressure, low-density lipoprotein, international normalized ratio, and glycosylated hemoglobin target levels, and delivery of appropriate treatment for poststroke depression along with a composite measure of achieved outcomes. Results—Median risk-standardized composite rate of defect-free care at discharge was 79%. Median risk-standardized postdischarge rates of achieving goal were 56% for blood pressure, 36% for low-density lipoprotein, 41% for international normalized ratio, 40% for glycosylated hemoglobin, and 39% for depression management and the median risk-standardized composite 6-month outcome rate was 44%. The hospital composite rate of defect-free care at discharge was correlated with meeting the low-density lipoprotein goal (r=0.31; P=0.007) and depression management (r=0.27; P=0.03) goal but was not correlated with blood pressure, international normalized ratio, glycosylated hemoglobin goals, nor with the composite measure of achieved postdischarge outcomes (probability values >0.13). Conclusions—Hospital discharge care quality was not consistently correlated with ambulatory care quality

Factors influencing completion of multi-dose vaccine schedules in adolescents: a systematic review

Background: Completion of multiple dose vaccine schedules is crucial to ensure a protective immune response, and maximise vaccine cost-effectiveness. While barriers and facilitators to vaccine uptake have recently been reviewed, there is no comprehensive review of factors influencing subsequent adherence or completion, which is key to achieving vaccine effectiveness. This study identifies and summarises the literature on factors affecting completion of multi-dose vaccine schedules by adolescents. Methods: Ten online databases and four websites were searched (February 2014). Studies with analysis of factors predicting completion of multi-dose vaccines were included. Study participants within 9-19 years of age were included in the review. The defined outcome was completion of the vaccine series within 1 year among those who received the first dose. Results: Overall, 6159 abstracts were screened, and 502 full texts were reviewed. Sixty one studies were eligible for this review. All except two were set in high-income countries. Included studies evaluated human papillomavirus vaccine, hepatitis A, hepatitis B, and varicella vaccines. Reported vaccine completion rates, among those who initiated vaccination, ranged from 27 % to over 90 %. Minority racial or ethnic groups and inadequate health insurance coverage were risk factors for low completion, irrespective of initiation rates. Parental healthcare seeking behaviour was positively associated with completion. Vaccine delivery in schools was associated with higher completion than delivery in the community or health facilities. Gender, prior healthcare use and socio-economic status rarely remained significant risks or protective factors in multivariate analysis. Conclusions: Almost all studies investigating factors affecting completion have been carried out in developed countries and investigate a limited range of variables. Increased understanding of barriers to completion in adolescents will be invaluable to future new vaccine introductions and the further development of an adolescent health platform