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1.  Focus-on-Teens, sexual risk-reduction intervention for high-school adolescents: impact on knowledge, change of risk-behaviours, and prevalence of sexually transmitted diseases 
International journal of STD & AIDS  2008;19(10):704-710.
A community-based intervention, Focus-on-Kids (FOK) has demonstrated risk-behaviour reduction of urban youth. We modified FOK to Focus-on-Teens (FOT) for high schools. High school adolescents (n = 1190) were enrolled over successive school semesters. The small-group sessions were presented during the school-lunch hours. Confidential surveys were conducted at baseline, immediate, six-, and 12-month postintervention for demographics, parental communication/monitoring, sexual risk behaviours and sexually transmitted diseases (STDs)/HIV/condom-usage knowledge. Sexually active participants were encouraged to volunteer for urine-based STDs testing at the School-Based Health Centres. Many (47.4%) students reported having had sexual intercourse at baseline. Overall behaviours changed towards ‘safer’ sex behaviours (intent-to-use and using condoms, communicating with partner/parents about sex/condoms/STDs) with time (P < 0.05). Proportion of students with complete correct knowledge of STDs/HIV increased to 88% at time 4 from 80% at baseline after adjusting for age, gender and sexual activity (P < 0.05). High prevalence of STDs was detected in 875 participants who reported for urine testing at time 1: trichomonas, 11.8%; chlamydia, 10.1% and gonorrhoea, 4.1%. Prevalence decreased significantly for 310 participants who re-tested; chlamydia: 27.4% to 6.1% and gonorrhoea: 11.3% to 3.2%. FOT was successfully implemented as an STDs/HIV risk-reduction intervention. Sustained improvements of knowledge about STDs/HIV/condom usage, decreases in sexual risk behaviours supported the effectiveness of this intervention.
PMCID: PMC4800004  PMID: 18824625
adolescents; STDs; behavioural intervention; HIV; high schools
2.  Directional charge separation in isolated organic semiconductor crystalline nanowires 
Nature Communications  2016;7:10629.
One of the fundamental design paradigms in organic photovoltaic device engineering is based on the idea that charge separation is an extrinsically driven process requiring an interface for exciton fission. This idea has driven an enormous materials science engineering effort focused on construction of domain sizes commensurate with a nominal exciton diffusion length of order 10 nm. Here, we show that polarized optical excitation of isolated pristine crystalline nanowires of a small molecule n-type organic semiconductor, 7,8,15,16-tetraazaterrylene, generates a significant population of charge-separated polaron pairs along the π-stacking direction. Charge separation was signalled by pronounced power-law photoluminescence decay polarized along the same axis. In the transverse direction, we observed exponential decay associated with excitons localized on individual monomers. We propose that this effect derives from an intrinsic directional charge-transfer interaction that can ultimately be programmed by molecular packing geometry.
Photo-induced charge separation in organic semiconductors usually occurs at interfaces between electron donors and acceptors. Here, the authors show using photoluminescence measurements that charge separation is intrinsic and directional in organic crystalline nanowires made of stacked monomers.
PMCID: PMC4773394  PMID: 26912040
3.  Understanding vulnerability to self-harm in times of economic hardship and austerity: a qualitative study 
BMJ Open  2016;6(2):e010131.
Self-harm and suicide increase in times of economic recession, but little is known about why people self-harm when in financial difficulty, and in what circumstances self-harm occurs. This study aimed to understand events and experiences leading to the episode of self-harm and to identify opportunities for prevention or mitigation of distress.
Participants’ homes or university rooms.
19 people who had attended hospital following self-harm in two UK cities and who specifically cited job loss, economic hardship or the impact of austerity measures as a causal or contributory factor.
Primary and secondary outcome measures
Semistructured, in-depth interviews. Interviews were audio recorded, transcribed and analysed cross-sectionally and as case studies.
Study participants described experiences of severe economic hardship; being unable to find employment or losing jobs, debt, housing problems and benefit sanctions. In many cases problems accumulated and felt unresolvable. For others an event, such as a call from a debt collector or benefit change triggered the self-harm. Participants also reported other current or past difficulties, including abuse, neglect, bullying, domestic violence, mental health problems, relationship difficulties, bereavements and low self-esteem. These contributed to their sense of despair and worthlessness and increased their vulnerability to self-harm. Participants struggled to gain the practical help they felt they needed for their economic difficulties or therapeutic support that might have helped with their other co-existing or historically damaging experiences.
Economic hardships resulting from the recession and austerity measures accumulated or acted as a ‘final straw’ to trigger self-harm, often in the context of co-existing or historically damaging life-experiences. Interventions to mitigate these effects should include providing practical advice about economic issues before difficulties become insurmountable and providing appropriate psychosocial support for vulnerable individuals.
PMCID: PMC4762121  PMID: 26888729
Neuro-Oncology  2014;16(Suppl 2):ii8.
Dysregulation of epigenetic mechanisms, together with genetic mutations, is an essential driver in the progression of malignant gliomas. Polycomb group proteins (PcG) are chromatin associated proteins that play an essential role in epigenetic regulation of gene expression. We have recently demonstrated that conditional overexpression of Bmi1 in neural stem cells (NSC) increased their proliferation and self-renewal while overexpression of Bmi1 in intermediate progenitors committed toward the neuronal lineage triggered apoptosis. At the mechanistic level, in Bmi1-overexpressing NSC we observed downregulation of both the p21/Foxg1 and the ink4a/arf pathways, the latter of which coincided with the accumulation of H3K27me3 at the promoter region of the p16ink4a gene, thus indicating the key role of this modification as downstream effector of Bmi1-induced silencing. Moreover, we have shown that a similar mechanism is also responsible for silencing expression of Survivin, a key antiapoptotic factor, in committed neuronal progenitors, thereby leading to their apoptosis. Together, this convergent evidence points to increased trimethylation of H3K27 as a core mechanism mediating the functional outcome of Bmi1 upregulation. Bmi1 is overexpressed in a significant proportion of high grade gliomas and a wealth of suggestive evidence linking perturbations in H3K27 methylation to the development of these tumours exist, although it is still unclear how aberrant H3K27me3 contributes to gliomagenesis. Here, we used genetically engineered mouse models to study overexpression of PcG gene Bmi1 in NSC and GBM initiating cells (GBM-IC). ChIP followed by genome wide screening was carried out and the results analysed in combination with gene expression as assessed by RNASeq. We show that Bmi1-mediated regulation of the expression of Survivin was strikingly similar in GBM-IC as observed in NSC. mGBM-IC isolated from a mouse model of glioblastoma express similar level of Bmi1 as detected in NSC isolated from NestinCre;STOPFloxBmi1 and knock down of Bmi1 significantly hampers proliferation of mGBM-IC. Similar to what observed in non-neoplastic NSC overexpressing Bmi1 a significant reduction of H3K27me3 was seen in these cells upon Bmi1 knockdown. Genome wide ChIPSeq analysis for H3K27me3 and RNASeq performed on NSC overexpressing Bmi1 and GBM-IC expressing similar level of Bmi1 allowed us to set these results in the wider context of the global epigenetic regulation of gene expression mediated by Bmi1. Elucidating the molecular mechanisms of the epigenetic dysregulation observed in high grade gliomas is essential for the identification of novel biomarkers of early stage tumours and also offers an opportunity to identify novel druggable targets or drug repositioning opportunities for more effective therapies.
PMCID: PMC4185638
5.  Hypothalamic QRFP: Regulation of Food Intake and Fat Selection 
QRFP, a member of the RFamide-related peptide family, is a strongly conserved hypothalamic neuropeptide that has been characterized in various species. Prepro-QRFP mRNA expression is localized to select regions of the hypothalamus, which are involved in the regulation of feeding behavior. The localization of the peptide precursor has led to the assessment of QRFP on feeding behaviors and the orexigenic effects of QRFP have been detected in mice, rats, and birds. QRFP acts in a macronutrient specific manner in satiated rats to increase the intake of a high fat diet, but not the intake of a low fat diet, and increases the intake of chow in food-restricted rats. Studies suggest that QRFP’s effects on food intake are mediated by the adiposity signal, leptin, and hypothalamic neuropeptides. Additionally, QRFP regulates the expression and release of hypothalamic Neuropeptide Y and proopiomelanocortin/α-Melanocyte-Stimulating Hormone. QRFP binds to receptors throughout the brain, including regions associated with food intake and reward. Taken together, these data suggest that QRFP is a mediator of motivated behaviors, particularly the drive to ingest high fat food. The present review discusses the role of QRFP in the regulation of feeding behavior, with emphasis on the intake of dietary fat.
PMCID: PMC4239704  PMID: 23979792
high fat diet; neuropeptide Y; agouti-related peptide; arcuate nucleus; ventromedial hypothalamus
6.  DNA-based species detection capabilities using laser transmission spectroscopy 
Early detection of invasive species is critical for effective biocontrol to mitigate potential ecological and economic damage. Laser transmission spectroscopy (LTS) is a powerful solution offering real-time, DNA-based species detection in the field. LTS can measure the size, shape and number of nanoparticles in a solution and was used here to detect size shifts resulting from hybridization of the polymerase chain reaction product to nanoparticles functionalized with species-specific oligonucleotide probes or with the species-specific oligonucleotide probes alone. We carried out a series of DNA detection experiments using the invasive freshwater quagga mussel (Dreissena bugensis) to evaluate the capability of the LTS platform for invasive species detection. Specifically, we tested LTS sensitivity to (i) DNA concentrations of a single target species, (ii) the presence of a target species within a mixed sample of other closely related species, (iii) species-specific functionalized nanoparticles versus species-specific oligonucleotide probes alone, and (iv) amplified DNA fragments versus unamplified genomic DNA. We demonstrate that LTS is a highly sensitive technique for rapid target species detection, with detection limits in the picomolar range, capable of successful identification in multispecies samples containing target and non-target species DNA. These results indicate that the LTS DNA detection platform will be useful for field application of target species. Additionally, we find that LTS detection is effective with species-specific oligonucleotide tags alone or when they are attached to polystyrene nanobeads and with both amplified and unamplified DNA, indicating that the technique may also have versatility for broader applications.
PMCID: PMC3565792  PMID: 23015524
DNA detection; Dreissena; polymerase chain reaction; laser transmission spectroscopy; ballast; invasive species
7.  Adherence to a Mediterranean diet and Alzheimer's disease risk in an Australian population 
Translational Psychiatry  2012;2(10):e164-.
The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD and MCI status in multinominal logistic regression models that were adjusted for cohort age, sex, country of birth, education, apolipoprotein E genotype, total caloric intake, current smoking status, body mass index, history of diabetes, hypertension, angina, heart attack and stroke. There was a significant difference in adherence to the MeDi between HC and AD subjects (P<0.001), and in adherence between HC and MCI subjects (P<0.05). MeDi is associated with change in Mini-Mental State Examination score over an 18-month time period (P<0.05) in HCs. We conclude that in this Australian cohort, AD and MCI participants had a lower adherence to the MeDi than HC participants.
PMCID: PMC3565821  PMID: 23032941
AIBL; Alzheimer's disease; Australia; Mediterranean diet; MCI
8.  Dynamics of maternal and paternal effects on embryo and seed development in wild radish (Raphanus sativus) 
Annals of Botany  2010;106(2):309-319.
Background and Aims
Variability in embryo development can influence the rate of seed maturation and seed size, which may have an impact on offspring fitness. While it is expected that embryo development will be under maternal control, more controversial hypotheses suggest that the pollen donor and the embryo itself may influence development. These latter possibilities are, however, poorly studied. Characteristics of 10-d-old embryos and seeds of wild radish (Raphanus sativus) were examined to address: (a) the effects of maternal plant and pollen donor on development; (b) the effects of earlier reproductive events (pollen tube growth and fertilization) on embryos and seeds, and the influence of embryo size on mature seed mass; (c) the effect of water stress on embryos and seeds; (d) the effect of stress on correlations of embryo and seed characteristics with earlier and later reproductive events and stages; and (e) changes in maternal and paternal effects on embryo and seed characteristics during development.
Eight maternal plants (two each from four families) and four pollen donors were crossed and developing gynoecia were collected at 10 d post-pollination. Half of the maternal plants experienced water stress. Characteristics of embryos and seeds were summarized and also compared with earlier and later developmental stages.
Key Results
In addition to the expected effects of the maternal plants, all embryo characters differed among pollen donors. Paternal effects varied over time, suggesting that there are windows of opportunity for pollen donors to influence embryo development. Water-stress treatment altered embryo characteristics; embryos were smaller and less developed. In addition, correlations of embryo characteristics with earlier and later stages changed dramatically with water stress.
The expected maternal effects on embryo development were observed, but there was also evidence for an early paternal role. The relative effects of these controls may change over time. Thus, there may be times in development when selection on the maternal, paternal or embryo contributions to development are more and less likely.
PMCID: PMC2908165  PMID: 20519237
Raphanus sativus; embryo development; maternal effects; paternal effects; seed development; seed size; water stress; wild radish
9.  Continuous positive airway pressure reduces daytime sleepiness in mild to moderate obstructive sleep apnoea: a meta‐analysis 
Thorax  2006;61(5):430-434.
Obstructive sleep apnoea syndrome (OSAS) affects an estimated 2–4% of the middle aged population. Meta‐analyses of randomised controlled trials have shown that the severe presentation of the syndrome (apnoea hypopnoea index (AHI) >30/hour) is effectively treated with continuous positive airway pressure (CPAP). Until recently there have been insufficient data to determine whether CPAP improves sleepiness in the larger subgroup with mild to moderate OSAS (AHI 5–30/hour).
A systematic search of Medline and a hand search identified seven randomised controlled trials where CPAP was compared with either a placebo or with conservative management in the treatment of mild to moderate OSAS (AHI 5–30/hour). All trials used the Epworth Sleepiness Scale (ESS), four used the Multiple Sleep Latency Test (MSLT), and three used the Maintenance of Wakefulness Test (MWT) to measure sleepiness.
Meta‐analyses indicated that CPAP significantly reduced subjective daytime sleepiness (ESS) by 1.2 points (95% CI 0.5 to 1.9, p = 0.001), improved objective daytime wakefulness (MWT) by 2.1 minutes (95% CI 0.5 to 3.7, p = 0.011), but did not affect objective daytime sleepiness (MSLT, mean benefit −0.2 minutes, 95% CI −1.0 to 0.6, p = 0.6). The two significant effects were small (effect size <0.30).
CPAP elicits small improvements in subjective sleepiness and objective wakefulness in people with mild to moderate OSAS. However, the effects on sleepiness are of limited clinical significance.
PMCID: PMC2111183  PMID: 16467072
continuous positive airway pressure; obstructive sleep apnoea; meta‐analysis
10.  Clinical importance of the Step 3 choice in asthma 
Thorax  2006;61(2):180-181.
PMCID: PMC2104568  PMID: 16443711
asthma; long acting beta agonists; inhaled corticosteroids; inflammation
PMCID: PMC1765644  PMID: 14645459
14.  Botulinum toxin and spasticity 
PMCID: PMC1737055  PMID: 10896682
15.  Botulinum Toxin in the Treatment of Cerebral Palsy. 
PMCID: PMC1736963  PMID: 10811713
16.  Botulinum toxin (Dysport®) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study 
OBJECTIVE—To define a safe and effective dose of Dysport for treating hip adductor spasticity.
METHODS—Patients with definite or probable multiple sclerosis, and disabling spasticity affecting the hip adductor muscles of both legs, were randomised to one of four treatment groups. Dysport (500, 1000, or 1500 Units), or placebo was administered by intramuscular injection to these muscles. Patients were assessed at entry, and 2, 4 (primary analysis time-point), 8, and 12 weeks post-treatment.
RESULTS—A total of 74 patients were recruited. Treatment groups were generally well matched at entry. The primary efficacy variables—passive hip abduction and distance between the knees—improved for all groups. The improvement in distance between the knees for the 1500 Unit group was significantly greater than placebo (p=0.02). Spasm frequency was reduced in all groups, but muscle tone was reduced in the Dysport groups only. Pain was reduced in all groups, but improvements in hygiene scores were evident only in the 1000Unit and 1500 Unit groups. Duration of benefit was significantly longer than placebo for all Dysport groups (p<0.05). Adverse events were reported by 32/58 (55%) Dysport patients, and by 10/16 (63%) placebo patients. Compared with the two lower dose groups, twice as many adverse events were reported by the 1500 Unit group (2.7/patient). The incidence of muscle weakness was higher for the 1500 Unit group (36%) than for placebo (6%). The response to treatment was considered positive by two thirds of the patients in the 500 Unit group, and by about half the patients in the other groups.
CONCLUSION—Dysport reduced the degree of hip adductor spasticity associated with multiple sclerosis, and this benefit was evident despite the concomitant use of oral antispasticity medication and analgesics. Although evidence for a dose response effect was not statistically significant, there was a clear trend towards greater efficacy and duration of effect with higher doses of Dysport. Dysport treatment was well tolerated, with no major side effects seen at doses up to 1500 Units. The optimal dose for hip adductor spasticity seems to be 500-1000 Units, divided between both legs.

PMCID: PMC1736956  PMID: 10811692
18.  Integration of radiographic images with an electronic medical record. 
Radiographic images are important and expensive diagnostic tests. However, the provider caring for the patient often does not review the images directly due to time constraints. Institutions can use picture archiving and communications systems to make images more available to the provider, but this may not be the best solution. We integrated radiographic image review into the Regenstrief Medical Record System in order to address this problem. To achieve adequate performance, we store JPEG compressed images directly in the RMRS. Currently, physicians review about 5% of all radiographic studies using the RMRS image review function.
PMCID: PMC2243643  PMID: 11825241
19.  Representing and querying conceptual graphs with relational database management systems is possible. 
This is an experimental study on the feasibility of maintaining medical concept dictionaries in production grade relational database management systems (RDBMS.) In the past, RDBMS did not support transitive relational structures and had therefore been unsuitable for managing knowledge bases. The revised SQL-99 standard, however, may change this. In this paper we show that modern RDBMS that support recursive queries are capable of querying transitive relationships in a generic data model. We show a simple but efficient indexed representation of transitive closure. We could confirm that even challenging combined transitive relationships can be queried in SQL.
PMCID: PMC2243450  PMID: 11825256
20.  Evaluating scientific impact. 
Environmental Health Perspectives  2000;108(9):A392-A393.
PMCID: PMC2556936  PMID: 11017900
21.  Effective audit trails--a taxonomy for determination of information requirements. 
Current methods of detecting confidentiality breaches in electronic medical record systems are inadequate, partially due to the lack of necessary information at the point of audit trail analysis. In order to determine the information requirements for effective audit trail analysis, we have formulated a taxonomy of confidentiality breaches. By considering scenarios in which an inappropriate access might occur, we have identified "indicators" of confidentiality breaches, which may be thought of as evidence suggesting the possibility that a confidentiality breach has occurred. The collection of facts needed to describe the indicators provides insight into the types of information needed to improve confidentiality breach detection. Much of the information needed is unlikely to be available in the patient record. Research is needed exploring means of collecting and utilizing information from sources other than the patient record for use in improving patient information security.
PMCID: PMC2232638  PMID: 10566442
22.  Using external data sources to improve audit trail analysis. 
Audit trail analysis is the primary means of detection of inappropriate use of the medical record. While audit logs contain large amounts of information, the information required to determine useful user-patient relationships is often not present. Adequate information isn't present because most audit trail analysis systems rely on the limited information available within the medical record system. We report a feature of the STAR (System for Text Archive and Retrieval) audit analysis system where information available in the medical record is augmented with external information sources such as: database sources, Light-weight Directory Access Protocol (LDAP) server sources, and World Wide Web (WWW) database sources. We discuss several issues that arise when combining the information from each of these disparate information sources. Furthermore, we explain how the enhanced person specific information obtained can be used to determine user-patient relationships that might signify a motive for inappropriately accessing a patient's medical record.
PMCID: PMC2232542  PMID: 10566469
24.  Large scale database scrubbing using object oriented software components. 
Now that case managers, quality improvement teams, and researchers use medical databases extensively, the ability to share and disseminate such databases while maintaining patient confidentiality is paramount. A process called scrubbing addresses this problem by removing personally identifying information while keeping the integrity of the medical information intact. Scrubbing entire databases, containing multiple tables, requires that the implicit relationships between data elements in different tables of the database be maintained. To address this issue we developed DBScrub, a Java program that interfaces with any JDBC compliant database and scrubs the database while maintaining the implicit relationships within it. DBScrub uses a small number of highly configurable object-oriented software components to carry out the scrubbing. We describe the structure of these software components and how they maintain the implicit relationships within the database.
PMCID: PMC2232311  PMID: 9929271
25.  A 3-(3-hydroxyphenyl)propionic acid catabolic pathway in Rhodococcus globerulus PWD1: cloning and characterization of the hpp operon. 
Journal of Bacteriology  1997;179(19):6145-6153.
Rhodococcus globerulus PWD1, a soil isolate from a polluted site in The Netherlands, is able to degrade a broad range of aromatic compounds. A novel gene cluster which appears to encode a pathway for the degradation of phenolic acids such as 3-(3-hydroxyphenyl)propionate (3HPP) has been cloned from the chromosome of this organism. Sequence analysis of a 7-kb region identified five open reading frames (ORFs). Analysis of mRNA showed that the genes were expressed during growth on 3HPP and 3-hydroxyphenylacetate (3HPA) but not during growth on m-cresol or succinate. The first ORF, hppA, which appears to be separately transcribed, had considerable amino acid identity with a number of hydroxylases. Transcriptional analysis indicates that the next four ORFs, hppCBKR, which are tightly clustered, constitute a single operon. These genes appear to encode a hydroxymuconic semialdehyde hydrolase (HppC), an extradiol dioxygenase (HppB), a membrane transport protein (HppK), and a member of the IclR family of regulatory proteins (HppR). The activities of HppB and HppC have been confirmed by enzyme assay of Escherichia coli hosts. The substrate specificity of HppB expressed from the cloned gene matches that of the meta-cleavage dioxygenase expressed from wild-type Rhodococcus grown on both 3HPP and 3HPA and is considerably more active against acid than against neutral catechols. The deduced amino acid sequences of the gene products have a recognizable homology with a broad range of enzymes and proteins involved in biodegradation and appear most similar to the mhp operon from E. coli K-12, which also encodes the degradation of 3HPP.
PMCID: PMC179521  PMID: 9324265

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