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1.  Global numbers of infection and disease burden of soil transmitted helminth infections in 2010 
Parasites & Vectors  2014;7:37.
Background
Quantifying the burden of parasitic diseases in relation to other diseases and injuries requires reliable estimates of prevalence for each disease and an analytic framework within which to estimate attributable morbidity and mortality. Here we use data included in the Global Atlas of Helminth Infection to derive new global estimates of numbers infected with intestinal nematodes (soil-transmitted helminths, STH: Ascaris lumbricoides, Trichuris trichiura and the hookworms) and use disability-adjusted life years (DALYs) to estimate disease burden.
Methods
Prevalence data for 6,091 locations in 118 countries were sourced and used to estimate age-stratified mean prevalence for sub-national administrative units via a combination of model-based geostatistics (for sub-Saharan Africa) and empirical approaches (for all other regions). Geographical variation in infection prevalence within these units was approximated using modelled logit-normal distributions, and numbers of individuals with infection intensities above given thresholds estimated for each species using negative binomial distributions and age-specific worm/egg burden thresholds. Finally, age-stratified prevalence estimates for each level of infection intensity were incorporated into the Global Burden of Disease Study 2010 analytic framework to estimate the global burden of morbidity and mortality associated with each STH infection.
Results
Globally, an estimated 438.9 million people (95% Credible Interval (CI), 406.3 - 480.2 million) were infected with hookworm in 2010, 819.0 million (95% CI, 771.7 – 891.6 million) with A. lumbricoides and 464.6 million (95% CI, 429.6 – 508.0 million) with T. trichiura. Of the 4.98 million years lived with disability (YLDs) attributable to STH, 65% were attributable to hookworm, 22% to A. lumbricoides and the remaining 13% to T. trichiura. The vast majority of STH infections (67%) and YLDs (68%) occurred in Asia. When considering YLDs relative to total populations at risk however, the burden distribution varied more considerably within major global regions than between them.
Conclusion
Improvements in the cartography of helminth infection, combined with mathematical modelling approaches, have resulted in the most comprehensive contemporary estimates for the public health burden of STH. These numbers form an important benchmark upon which to evaluate future scale-up of major control efforts.
doi:10.1186/1756-3305-7-37
PMCID: PMC3905661  PMID: 24447578
Soil-transmitted helminths; Ascaris lumbricoides; Trichuris trichiura; Hookworm; Disease burden; Disability-adjusted life years
3.  “Old Dogs” and New Skills: How Clinician Characteristics Relate to Motivational Interviewing Skills Before, During, and After Training 
Objective
The relationships between the occupational, educational, and verbal-cognitive characteristics of health care professionals and their Motivational Interviewing (MI) skills before, during, and after training were investigated.
Method
Fifty-eight community-based addiction clinicians (M = 42.1 yrs., SD =10.0; 66% Female) were assessed prior to enrolling in a two-day MI training workshop and being randomized to one of three post-workshop supervision programs: live supervision via tele-conferencing (TCS), standard tape-based supervision (Tape), or workshop training alone. Audiotaped sessions with clients were rated for MI skillfulness with the Motivational Interviewing Treatment Integrity (MITI) coding system v 2.0 at pre-workshop and 1, 8, and 20 weeks post-workshop. Correlation coefficients and generalized linear models were used to test the relationships between clinician characteristics and MI skill at each assessment point.
Results
Baseline MI skill levels were the most robust predictors of pre- and post-supervision performances. Clinician characteristics were associated with MI Spirit and reflective listening skill throughout training and moderated the effect of post-workshop supervision method on MI skill. TCS, which provided immediate feedback during practice sessions, was most effective for increasing MI Spirit and reflective listening among clinicians with no graduate degree and stronger vocabulary performances. Tape supervision was more effective for increasing these skills among clinicians with a graduate degree. Further, TCS and Tape were most likely to enhance MI Spirit among clinicians with low average to average verbal and abstract reasoning performances.
Conclusions
Clinician attributes influence the effectiveness of methods used to promote the acquisition of evidence-based practices among community-based practitioners.
doi:10.1037/a0028362
PMCID: PMC3928150  PMID: 22563640
Motivational Interviewing; Clinician Training; Clinical Supervision
5.  Comparing the Performance of Cluster Random Sampling and Integrated Threshold Mapping for Targeting Trachoma Control, Using Computer Simulation 
Background
Implementation of trachoma control strategies requires reliable district-level estimates of trachomatous inflammation–follicular (TF), generally collected using the recommended gold-standard cluster randomized surveys (CRS). Integrated Threshold Mapping (ITM) has been proposed as an integrated and cost-effective means of rapidly surveying trachoma in order to classify districts according to treatment thresholds. ITM differs from CRS in a number of important ways, including the use of a school-based sampling platform for children aged 1–9 and a different age distribution of participants. This study uses computerised sampling simulations to compare the performance of these survey designs and evaluate the impact of varying key parameters.
Methodology/Principal Findings
Realistic pseudo gold standard data for 100 districts were generated that maintained the relative risk of disease between important sub-groups and incorporated empirical estimates of disease clustering at the household, village and district level. To simulate the different sampling approaches, 20 clusters were selected from each district, with individuals sampled according to the protocol for ITM and CRS. Results showed that ITM generally under-estimated the true prevalence of TF over a range of epidemiological settings and introduced more district misclassification according to treatment thresholds than did CRS. However, the extent of underestimation and resulting misclassification was found to be dependent on three main factors: (i) the district prevalence of TF; (ii) the relative risk of TF between enrolled and non-enrolled children within clusters; and (iii) the enrollment rate in schools.
Conclusions/Significance
Although in some contexts the two methodologies may be equivalent, ITM can introduce a bias-dependent shift as prevalence of TF increases, resulting in a greater risk of misclassification around treatment thresholds. In addition to strengthening the evidence base around choice of trachoma survey methodologies, this study illustrates the use of a simulated approach in addressing operational research questions for trachoma but also other NTDs.
Author Summary
Reliable district-level prevalence estimates of active trachoma are essential to targeting control interventions. While cluster randomised surveys (CRS) remain the recommended strategy for obtaining these estimates, more rapid and cost-effective methods that can be integrated with other diseases are under investigation. One proposed method is Integrated Threshold Mapping (ITM), which incorporates a school-based platform into the sampling protocol. This study uses a computerised sampling approach to evaluate whether ITM and CRS are equivalent, and explore the impact of varying key parameters on the performance of these sampling methodologies. The results from these simulations reflect a known limitation of school-based sampling: that resulting prevalence estimates are unreliable when the enrollment is low and/or the risk of disease in schools differs from communities. However, quantification of the performance of ITM at the district level highlights the variation in performance in different contexts and provides important information for national control programmes. The results from this study strengthen the evidence base around trachoma sampling methodologies and demonstrate the advantages of using a simulated approach to evaluate different sampling scenarios.
doi:10.1371/journal.pntd.0002389
PMCID: PMC3749968  PMID: 23991238
6.  The Geographical Distribution and Burden of Trachoma in Africa 
Background
There remains a lack of epidemiological data on the geographical distribution of trachoma to support global mapping and scale up of interventions for the elimination of trachoma. The Global Atlas of Trachoma (GAT) was launched in 2011 to address these needs and provide standardised, updated and accessible maps. This paper uses data included in the GAT to describe the geographical distribution and burden of trachoma in Africa.
Methods
Data assembly used structured searches of published and unpublished literature to identify cross-sectional epidemiological data on the burden of trachoma since 1980. Survey data were abstracted into a standardised database and mapped using geographical information systems (GIS) software. The characteristics of all surveys were summarized by country according to data source, time period, and survey methodology. Estimates of the current population at risk were calculated for each country and stratified by endemicity class.
Results
At the time of writing, 1342 records are included in the database representing surveys conducted between 1985 and 2012. These data were provided by direct contact with national control programmes and academic researchers (67%), peer-reviewed publications (17%) and unpublished reports or theses (16%). Prevalence data on active trachoma are available in 29 of the 33 countries in Africa classified as endemic for trachoma, and 1095 (20.6%) districts have representative data collected through population-based prevalence surveys. The highest prevalence of active trachoma and trichiasis remains in the Sahel area of West Africa and Savannah areas of East and Central Africa and an estimated 129.4 million people live in areas of Africa confirmed to be trachoma endemic.
Conclusion
The Global Atlas of Trachoma provides the most contemporary and comprehensive summary of the burden of trachoma within Africa. The GAT highlights where future mapping is required and provides an important planning tool for scale-up and surveillance of trachoma control.
Author Summary
In order to target resources and drugs to reach trachoma elimination targets by the year 2020, data on the burden of disease are required. Using prevalence data in African countries derived from the Global Atlas of Trachoma (GAT), the distribution of trachoma continues to be focused in East and West Sub-Saharan Africa, North Africa and a few endemic countries in Central Sub-Saharan Africa. Currently, 129.4 million people are estimated to live in areas that are confirmed to be trachoma endemic and 98 million are known to require access to the SAFE strategy. The maps and information presented in this work highlight the GAT as important open-access planning and advocacy tool for efforts to finalize trachoma mapping and assist national programmes in planning interventions.
doi:10.1371/journal.pntd.0002359
PMCID: PMC3738464  PMID: 23951378
7.  Impact of hookworm infection and deworming on anaemia in non-pregnant populations: a systematic review 
Objectives
To summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles, albendazole and mebendazole, on haemoglobin and anaemia in non-pregnant populations.
Methods
Electronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant studies published between 1980 and 2009, regardless of language, and researchers contacted about potential data. Haemoglobin concentration (Hb) was compared between uninfected individuals and individuals harbouring hookworm infections of different intensities, expressed as standardised mean differences (SMD) and 95% confidence intervals (CI). Meta-analysis of randomised control trials (RCTs) investigated the impact of treatment on Hb and anaemia.
Results
Twenty-three cross-sectional studies, six pre- and post-intervention studies and 14 trials were included. Among cross-sectional studies, moderate- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children, while all levels of infection intensity were associated with lower Hb in adults. Among RCTs using albendazole, impact of treatment corresponded to a 1.89 g/l increase (95%CI: 0.13–3.63) in mean Hb while mebendazole had no impact. There was a positive impact of 2.37 g/l (95%CI: 1.33–3.50) on mean Hb when albendazole was co-administered with praziquantel, but no apparent additional benefit of treatment with benzimidazoles combined with iron supplementation. The mean impact of treatment with benzimidazoles alone on moderate anaemia was small (relative risk (RR) 0.87) with a larger effect when combined with praziquantel (RR 0.61).
Conclusions
Anaemia is most strongly associated with moderate and heavy hookworm infection. The impact of anthelmintic treatment is greatest when albendazole is co-administered with praziquantel.
doi:10.1111/j.1365-3156.2010.02542.x
PMCID: PMC2916221  PMID: 20500563
hookworm; Necator americanus; Ancylostoma duodenale; anaemia; haemoglobin; anthelmintic treatment
8.  Training Substance Abuse Clinicians in Motivational Interviewing Using Live Supervision via Tele-conferencing 
Background
Training through traditional workshops is relatively ineffective for changing counseling practices. Tele-conferencing Supervision (TCS) was developed to provide remote, live supervision for training motivational interviewing (MI).
Method
97 community drug treatment counselors completed a 2-day MI workshop and were randomized to: live supervision via tele-conferencing (TCS; n=32), standard tape-based supervision (Tape; n=32), or workshop alone (Workshop; n=33). Supervision conditions received 5 weekly supervision sessions at their sites using actors as standard patients. Sessions with clients were rated for MI skill with the Motivational Interviewing Treatment Integrity (MITI) coding system pre-workshop and 1, 8, and 20 weeks post-workshop. Mixed effects linear models were used to test training condition on MI skill at 8 and 20 weeks.
Results
TCS scored better than Workshop on the MITI for Spirit (mean difference = 0.76; p < .0001; d = 1.01) and Empathy (mean difference = 0.68; p < .001; d = 0.74). Tape supervision fell between TCS and Workshop, with Tape superior to Workshop for Spirit (mean difference = 0.40; p < .05). TCS was superior to Workshop in reducing MI non-adherence and increasing MI adherence, and was superior to Workshp and Tape in increasing the reflection to question ratio. Tape was superior to TCS in increasing complex reflections. Percentage of counselors meeting proficiency differed significantly between training conditions for the most stringent threshold (Spirit and Empathy scores ≥ 6), and were modest, ranging from 13% to 67%, for TCS and Tape.
Conclusion
TCS shows promise for promoting new counseling behaviors following participation in workshop training. However, further work is needed to improve supervision methods in order to bring more clinicians to high levels of proficiency and facilitate the dissemination of evidence-based practices.
doi:10.1037/a0028176
PMCID: PMC3365649  PMID: 22506795
motivational interviewing; substance abuse; clinician training
9.  Impact of hookworm infection and deworming on anaemia in non-pregnant populations: a systematic review 
Summary
OBJECTIVES
To summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles, albendazole and mebendazole, on haemoglobin and anaemia in non-pregnant populations.
METHODS
Electronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant studies published between 1980 and 2009, regardless of language, and researchers contacted about potential data. Haemoglobin concentration (Hb) was compared between uninfected individuals and individuals harbouring hookworm infections of different intensities, expressed as standardised mean differences (SMD) and 95% confidence intervals (CI). Meta-analysis of randomised control trials (RCTs) investigated the impact of treatment on Hb and anaemia.
RESULTS
Twenty-three cross-sectional studies, six pre- and post-intervention studies and 14 trials were included. Among cross-sectional studies, moderate- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children, while all levels of infection intensity were associated with lower Hb in adults. Among RCTs using albendazole, impact of treatment corresponded to a 1.89 g/l increase (95%CI: 0.13–3.63) in mean Hb while mebendazole had no impact. There was a positive impact of 2.37 g/l (95%CI: 1.33–3.50) on mean Hb when albendazole was co-administered with praziquantel, but no apparent additional benefit of treatment with benzimidazoles combined with iron supplementation. The mean impact of treatment with benzimidazoles alone on moderate anaemia was small (relative risk (RR) 0.87) with a larger effect when combined with praziquantel (RR 0.61).
CONCLUSIONS
Anaemia is most strongly associated with moderate and heavy hookworm infection. The impact of anthelmintic treatment is greatest when albendazole is co-administered with praziquantel.
doi:10.1111/j.1365-3156.2010.02542.x
PMCID: PMC2916221  PMID: 20500563
hookworm; Necator americanus; Ancylostoma duodenale; anaemia; haemoglobin; anthelmintic treatment
10.  An updated atlas of human helminth infections: the example of East Africa 
Background
Reliable and updated maps of helminth (worm) infection distributions are essential to target control strategies to those populations in greatest need. Although many surveys have been conducted in endemic countries, the data are rarely available in a form that is accessible to policy makers and the managers of public health programmes. This is especially true in sub-Saharan Africa, where empirical data are seldom in the public domain. In an attempt to address the paucity of geographical information on helminth risk, this article describes the development of an updated global atlas of human helminth infection, showing the example of East Africa.
Methods
Empirical, cross-sectional estimates of infection prevalence conducted since 1980 were identified using electronic and manual search strategies of published and unpublished sources. A number of inclusion criteria were imposed for identified information, which was extracted into a standardized database. Details of survey population, diagnostic methods, sample size and numbers infected with schistosomes and soil-transmitted helminths were recorded. A unique identifier linked each record to an electronic copy of the source document, in portable document format. An attempt was made to identify the geographical location of each record using standardized geolocation procedures and the assembled data were incorporated into a geographical information system.
Results
At the time of writing, over 2,748 prevalence surveys were identified through multiple search strategies. Of these, 2,612 were able to be geolocated and mapped. More than half (58%) of included surveys were from grey literature or unpublished sources, underlining the importance of reviewing in-country sources. 66% of all surveys were conducted since 2000. Comprehensive, countrywide data are available for Burundi, Rwanda and Uganda. In contrast, information for Kenya and Tanzania is typically clustered in specific regions of the country, with few records from areas with very low population density and/or environmental conditions which are unfavourable for helminth transmission. Information is presented on the prevalence and geographical distribution for the major helminth species.
Conclusion
For all five countries, the information assembled in the current atlas provides the most reliable, up-to-date and comprehensive source of data on the distribution of common helminth infections to guide the rational implementation of control efforts.
doi:10.1186/1476-072X-8-42
PMCID: PMC2714505  PMID: 19589144
11.  Analysis of Antithrombotic Therapy After Cardioembolic Stroke Due to Atrial Fibrillation or Flutter 
Hospital Pharmacy  2013;48(2):127-133.
Background:
Guidelines recommend that all patients with atrial fibrillation and a history of ischemic stroke should receive an anticoagulant. Prior analyses show that warfarin is underutilized in most populations.
Objective:
To examine the use of antithrombotic and anticoagulant therapy in patients with atrial fibrillation or flutter during the index hospitalization for acute, ischemic stroke.
Methods:
Retrospective electronic medical record review of 200 patients treated at a tertiary care hospital with a primary ICD-9 code for ischemic stroke and a secondary ICD-9 code for atrial fibrillation or flutter. Exclusion criteria were active bleeding, pregnancy, age less than 18, pre-existing warfarin allergy, or dabigatran use.
Results:
Fifty-two percent of patients received at least one dose of warfarin during the index hospitalization. There was no relationship between CHADS2 score and likelihood of receiving warfarin (P > .05). There was no significant difference in adverse event rate in patients receiving warfarin compared to those receiving aspirin (3.8% vs 9.1%; P = .14), but the rate of hemorrhagic transformation was lower in patients receiving warfarin (1% vs 7%; P = .03). The composite of hemorrhagic stroke or hemorrhagic transformation was significantly lower in patients receiving bridging therapy (0% vs 11%; P = .03). Sixteen patients were readmitted for stroke within 3 months of discharge. Ten were readmitted for ischemic stroke, 3 for hemorrhagic stroke or hemorrhagic transformation, and 3 for systemic bleeding. Ten patients (62.5%) were receiving warfarin at readmission, but only one of these patients had a therapeutic INR.
Conclusions:
Warfarin was underutilized as secondary stroke prophylaxis in these high-risk patients. Bridging therapy appeared to be safe and was not associated with an increase in adverse events.
doi:10.1310/hpj4802-127
PMCID: PMC3839477  PMID: 24421450
anticoagulant; atrial fibrillation; atrial flutter; stroke; warfarin
12.  Alterations of Zinc Transporter Proteins ZnT-1, ZnT-4 and ZnT-6 in Preclinical Alzheimer's Disease Brain 
Our previous studies demonstrate alterations of zinc (Zn) transporter proteins ZnT-1, ZnT-4, and ZnT-6 in vulnerable brain regions of subjects with mild cognitive impairment (MCI), early and late stage Alzheimer's disease (AD) and suggest that disruptions of Zn homeostasis may play a role in the pathogenesis of AD. ZnT-1 exports Zn from the cytosol to extracellular compartments, ZnT-4 transports Zn from the cytosol to lysosomes and endosomes, and ZnT-6 sequesters Zn in the trans-Golgi network. A preclinical stage of AD (PCAD) has been described in which subjects show no overt clinical manifestations of AD but demonstrate significant AD pathology at autopsy. To determine if alterations of ZnT proteins occur in PCAD we measured ZnT-1, ZnT-4, and ZnT-6 in the hippocampus/parahippocampal gyrus (HPG) and cerebellum (CER) of 7 PCAD subjects and 7 age matched normal control (NC) subjects using Western blot analysis and immunohistochemistry. Our results show a significant decrease (P < 0.05) of ZnT-1 in HPG of PCAD subjects, along with an increase of ZnT-4 in PCAD CER and ZnT-6 in PCAD HPG, but a significant decrease in PCAD CER compared to NC subjects. Confocal microscopy of representative sections of HPG shows altered ZnTs are associated with neurons immunopositive for MC-1, a monoclonal antibody that identifies neurons early in formation of neurofibrillary tangles. Overall, our results suggest that alterations in Zn transport proteins may contribute to the pathology observed in PCAD subjects before onset of clinical symptoms.
doi:10.1111/j.1750-3639.2009.00283.x
PMCID: PMC3175637  PMID: 19371353
zinc transporter-1; zinc transporter-4; zinc transporter-6; preclinical Alzheimer's disease
14.  Spatial Modelling of Soil-Transmitted Helminth Infections in Kenya: A Disease Control Planning Tool 
Background
Implementation of control of parasitic diseases requires accurate, contemporary maps that provide intervention recommendations at policy-relevant spatial scales. To guide control of soil transmitted helminths (STHs), maps are required of the combined prevalence of infection, indicating where this prevalence exceeds an intervention threshold of 20%. Here we present a new approach for mapping the observed prevalence of STHs, using the example of Kenya in 2009.
Methods and Findings
Observed prevalence data for hookworm, Ascaris lumbricoides and Trichuris trichiura were assembled for 106,370 individuals from 945 cross-sectional surveys undertaken between 1974 and 2009. Ecological and climatic covariates were extracted from high-resolution satellite data and matched to survey locations. Bayesian space-time geostatistical models were developed for each species, and were used to interpolate the probability that infection prevalence exceeded the 20% threshold across the country for both 1989 and 2009. Maps for each species were integrated to estimate combined STH prevalence using the law of total probability and incorporating a correction factor to adjust for associations between species. Population census data were combined with risk models and projected to estimate the population at risk and requiring treatment in 2009. In most areas for 2009, there was high certainty that endemicity was below the 20% threshold, with areas of endemicity ≥20% located around the shores of Lake Victoria and on the coast. Comparison of the predicted distributions for 1989 and 2009 show how observed STH prevalence has gradually decreased over time. The model estimated that a total of 2.8 million school-age children live in districts which warrant mass treatment.
Conclusions
Bayesian space-time geostatistical models can be used to reliably estimate the combined observed prevalence of STH and suggest that a quarter of Kenya's school-aged children live in areas of high prevalence and warrant mass treatment. As control is successful in reducing infection levels, updated models can be used to refine decision making in helminth control.
Author Summary
Effective targeting of mass drug administration for the treatment of soil-transmitted helminths (STH) requires reliable, up-to-date maps that indicate where prevalence exceeds the 20% intervention threshold recommended by the World Health Organization. We present a new approach for mapping the prevalence of STH in Kenya, incorporating observed prevalence data from 945 cross-sectional surveys undertaken between 1974 and 2009. The distribution of each species was modelled using model-based geostatistics; models included information on environmental factors, the spatial distribution of existing surveys and when these surveys were conducted. Resulting risk maps were combined and linked with population data enabling estimation of the population at risk of any STH infection and requiring treatment in 2009. In most areas, there was high certainty that combined STH prevalence was below the 20% intervention threshold, with areas of high prevalence located around the shores of Lake Victoria and on the coast. Results also suggest that observed prevalence decreased over time and emphasise the importance of continued surveillance in areas where observed prevalence was historically high. We show how spatial modelling can be used to develop up-to-date maps of STH risk to help improve the precision of decision making in disease control.
doi:10.1371/journal.pntd.0000958
PMCID: PMC3035671  PMID: 21347451
15.  Medical and Mental Health Status Among Drug Dependent Patients Participating in a Smoking Cessation Treatment Study 
Journal of drug issues  2009;39(2):293-312.
Substance Abusers have a large number of medical and psychiatric problems, and 70–90% are smokers. The aim of this analysis was to examine the prevalence and correlates of medical and psychiatric problems in this sample of drug dependent patients who were participants in a multi-site study of smoking cessation interventions while engaged in substance abuse treatment. Descriptive analyses showed at baseline, 72.8% of participants had at least one medical problem and 64.1% had at least one psychiatric diagnosis. Medical problems correlated strongly with age, smoking severity, and pack-years; Psychiatric problems correlated with gender and ethnicity. Smoking cessation treatment was associated with a moderate reduction in the ASI Medical composite score. More research is needed on the possible effects of combined treatment of substance abuse and concurrent medical and psychiatric problems. Offering smoking cessation in conjunction with primary care may be a way to address the health needs of this population.
PMCID: PMC2902002  PMID: 20628556
16.  Establishing a training set through the visual analysis of crystallization trials. Part I: ∼150 000 images 
As part of a training set for automated image analysis, ∼150 000 images of crystallization experiments from 96 diverse macromolecules have been visually classified within seven categories. Outcomes and trends are analyzed.
Structural crystallography aims to provide a three-dimensional representation of macromolecules. Many parts of the multistep process to produce the three-dimensional structural model have been automated, especially through various structural genomics projects. A key step is the production of crystals for diffraction. The target macromolecule is combined with a large and chemically diverse set of cocktails with some leading ideally, but infrequently, to crystallization. A variety of outcomes will be observed during these screening experiments that typically require human interpretation for classification. Human interpretation is neither scalable nor objective, highlighting the need to develop an automatic computer-based image classification. As a first step towards automated image classification, 147 456 images representing crystallization experiments from 96 different macromolecular samples were manually classified. Each image was classified by three experts into seven predefined categories or their combinations. The resulting data where all three observers are in agreement provides one component of a truth set for the development and rigorous testing of automated image-classification systems and provides information about the chemical cocktails used for crystallization. In this paper, the details of this study are presented.
doi:10.1107/S0907444908028047
PMCID: PMC2631114  PMID: 19020350
crystallization; image classification
17.  The α1D-adrenergic receptor is expressed intracellularly and coupled to increases in intracellular calcium and reactive oxygen species in human aortic smooth muscle cells 
Background
The cellular localization of the α1D-adrenergic receptor (α1D-AR) is controversial. Studies in heterologous cell systems have shown that this receptor is expressed in intracellular compartments. Other studies show that dimerization with other ARs promotes the cell surface expression of the α1D-AR. To assess the cellular localization in vascular smooth muscle cells, we developed an adenoviral vector for the efficient expression of a GFP labeled α1D-AR. We also measured cellular localization with immunocytochemistry. Intracellular calcium levels, measurement of reactive oxygen species and contraction of the rat aorta were used as measures of functional activity.
Results
The adenovirally expressed α1D-AR was expressed in intracellular compartments in human aortic smooth muscle cells. The intracellular localization of the α1D-AR was also demonstrated with immunocytochemistry using an α1D-AR specific antibody. RT-PCR analysis detected mRNA transcripts corresponding to the α1A-α1B- and α1D-ARs in these aortic smooth muscle cells. Therefore, the presence of the other α1-ARs, and the potential for dimerization with these receptors, does not alter the intracellular expression of the α1D-AR. Despite the predominant intracellular localization in vascular smooth muscle cells, the α1D-AR remained signaling competent and mediated the phenylephrine-induced increases in intracellular calcium. The α1D-AR also was coupled to the generation of reactive oxygen species in smooth muscle cells. There is evidence from heterologous systems that the α1D-AR heterodimerizes with the β2-AR and that desensitization of the β2-AR results in α1D-AR desensitization. In the rat aorta, desensitization of the β2-AR had no effect on contractile responses mediated by the α1D-AR.
Conclusion
Our results suggest that the dimerization of the α1D-AR with other ARs does not alter the cellular expression or functional response characteristics of the α1D-AR.
doi:10.1186/1750-2187-3-6
PMCID: PMC2294121  PMID: 18304336
18.  A health policy for hearing impairment in older Australians: what should it include? 
Background
As in all western countries, Australia's older population experiences high levels of hearing impairment coupled with relatively low levels of hearing device usage. Poor hearing diminishes the quality of life of affected individuals and their families. This paper discusses how to improve Australian hearing health policies in order to better combat this impairment amongst older Australians.
Method
We searched the databases Medline, Meditext and Web of Science to find articles that discussed strategies and innovations to assist the hearing health of older people, and related this material to observations made during the Blue Mountains Hearing Study in NSW between 1997 and 2003.
Results and Discussion
The literature search identified five areas for inclusion in a comprehensive hearing health policy in Australia. These are: early intervention; addressing of hearing aid expense; the use of assisted listening devices; hearing rehabilitation, and; screening and education. Further research in Australia is critical if we are to develop a strong approach to the increasing prevalence of age-related hearing loss.
Conclusion
Australia needs to act now to address hearing impairment as it is a major cause of disability in those aged 55 and over. Federal and State governments should collaborate to construct a comprehensive hearing health policy that tackles poor levels of hearing health through early intervention, addressing hearing aid expense, encouraging the use of assisted listening devices, rehabilitation, screening and education. A good start would be to declare age related hearing impairment as a National Health Priority Area.
doi:10.1186/1743-8462-2-31
PMCID: PMC1326208  PMID: 16343355
19.  Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy. 
Neuro-Oncology  2002;4(1):26-38.
Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.
PMCID: PMC1920629  PMID: 11772430

Results 1-19 (19)