22 results on '"Brewer JL"'
Search Results
2. The Sources of Strength Australia project: A cluster randomised controlled trial of a peer-connectedness school-based program to promote help-seeking in adolescents.
- Author
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Calear AL, McCallum SM, Christensen H, Mackinnon AJ, Nicolopoulos A, Brewer JL, Werner-Seidler A, Morse AR, Kazan D, Farrer LM, Kampel L, and Batterham PJ
- Subjects
- Adolescent, Australia, Humans, Peer Group, Students, Schools, Suicide
- Abstract
Background: Suicide is a significant public health problem and there is a clear need for interventions to improve help seeking for suicide and psychological distress in young people. This trial aimed to assess the effectiveness of the school-based Sources of Strength program in increasing help-seeking intentions and behaviours in adolescents., Methods: A cluster, randomised controlled trial was conducted in 13 Australian secondary schools (N = 1633), with each school randomly allocated to the intervention (n = 7) or wait-list control condition (n = 6). Participants in the intervention condition received the Sources of Strength program over two years and all participants completed self-report measures of help-seeking intentions and behaviour at four time-points. Staff and students in the intervention condition also provided qualitative feedback on the perceived impact of the program., Results: Mixed model repeated measures analyses demonstrated no significant effect of the Sources of Strength program on help-seeking intentions or behaviour at post-intervention or 6- or 18-month follow-up. Staff and students reported, through qualitative feedback, that the program increased awareness of and openness to help seeking and promoted a common language and school community., Limitations: The current study only included self-report measures that may have been influenced by situational factors or biases., Conclusions: Although the Sources of Strength program may have increased awareness of help seeking, there was no evidence that it is effective in increasing help-seeking intentions or behaviours in this cohort. The program may be more suitable for schools in disadvantaged areas where there may be limited existing connections to trusted adults., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2022
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3. Playing With Your Phone in Class: Using Smartphones to Engage Nonparticipants in Simulation Sessions.
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Brewer JL, Lampotang S, Algarra NNN, and Taşdelen Teker G
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- Humans, Telephone, Cell Phone, Smartphone
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- 2021
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4. The Sources of Strength Australia Project: study protocol for a cluster randomised controlled trial.
- Author
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Calear AL, Brewer JL, Batterham PJ, Mackinnon A, Wyman PA, LoMurray M, Shand F, Kazan D, and Christensen H
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- Adaptation, Psychological, Adolescent, Age Factors, Australian Capital Territory, Child, Female, Health Knowledge, Attitudes, Practice, Humans, Male, New South Wales, Patient Acceptance of Health Care, Peer Group, Program Evaluation, Research Design, Risk Factors, Suicide psychology, Time Factors, Adolescent Behavior, Mental Health, School Health Services, Suicidal Ideation, Suicide Prevention
- Abstract
Background: The school system has been identified as an ideal setting for the implementation of prevention and early intervention programs for suicide. However, in Australia, suicide-prevention programs that are routinely delivered in the schools are lacking. Internationally, evidence exists for the effectiveness of peer-led interventions that take a social connectedness approach to improve help-seeking for suicide. The aim of the current trial is to test the effectiveness of the Sources of Strength program to promote help-seeking for suicide in adolescents in Australian high schools., Methods/design: This study is a two-arm, cluster-randomised, controlled trial that will compare the evidence-based Sources of Strength program to a wait-list control condition. Sixteen Australian high schools will be recruited to the trial, with all adolescents in years 7 to 10 (12-16 years of age) invited to participate. Peer leaders from intervention-condition schools will receive training in the Sources of Strength program and will integrate positive messages, across 3 months, with the support of adult advisors. Activities may take the form of class presentations, posters, videos, and messages on social media sites and will aim to change help-seeking norms, strengthen youth-adult connections, and promote positive coping. The primary outcome measure for the study is help-seeking intentions, whereas secondary outcomes include help-seeking behaviour, help-seeking attitudes and norms, referral of distressed peers, availability of adult help, positive coping, and suicidal behaviour. Data will be collected pre-intervention, post-intervention (after the initial 3 months of messaging), and at the end of the first (6-month follow-up) and the second year after implementation (18-month follow-up). Primary analyses will compare changes in help-seeking intentions for the intervention condition relative to the wait-list control condition using mixed-effect repeated-measures analyses to account for clustering within schools., Discussion: If proven effective, this universal social connectedness program for suicide could be more widely delivered in Australian high schools, providing a valuable new resource. The Sources of Strength program has the potential to significantly contribute to the mental health of young people in Australia by improving help-seeking for suicide. The findings from this research will also contribute to the evidence-base for peer-leadership programs internationally., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616000048482 . Registered on 19 January 2016.
- Published
- 2016
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5. Online screening and feedback to increase help-seeking for mental health problems: population-based randomised controlled trial.
- Author
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Batterham PJ, Calear AL, Sunderland M, Carragher N, and Brewer JL
- Abstract
Background: Community-based screening for mental health problems may increase service use through feedback to individuals about their severity of symptoms and provision of contacts for appropriate services., Aims: The effect of symptom feedback on service use was assessed. Secondary outcomes included symptom change and study attrition., Method: Using online recruitment, 2773 participants completed a comprehensive survey including screening for depression ( n =1366) or social anxiety ( n =1407). Across these two versions, approximately half ( n =1342) of the participants were then randomly allocated to receive tailored feedback. Participants were reassessed after 3 months (Australian New Zealand Clinical Trials Registry ANZCTR12614000324617)., Results: A negative effect of providing social anxiety feedback to individuals was observed, with significant reductions in professional service use. Greater attrition and lower intentions to seek help were also observed after feedback., Conclusions: Online mental health screening with feedback is not effective for promoting professional service use. Alternative models of online screening require further investigation., Declaration of Interest: None., Copyright and Usage: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
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- 2016
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6. Systematic item selection process applied to developing item pools for assessing multiple mental health problems.
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Batterham PJ, Brewer JL, Tjhin A, Sunderland M, Carragher N, and Calear AL
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- Algorithms, Comorbidity, Feedback, Health Status Indicators, Humans, Neuropsychological Tests, Surveys and Questionnaires, Mass Screening methods, Mental Disorders diagnosis
- Abstract
Objectives: Given high rates of comorbidity among mental disorders, better methods to rapidly screen across multiple mental disorders are needed. Building on existing Patient Reported Outcomes Measurement Information System (PROMIS) item banks, the present study aimed to select items to assess panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, adult attention-deficit hyperactivity disorder, substance use disorder, suicidal thoughts and behaviors, and psychosis., Study Design and Setting: A four-stage process to select items involved systematic literature searches, item refinement and standardization, obtaining feedback from consumers and experts, and reduction of item pools in preparation for calibration in a population-based sample., Results: From 6,900 items collected across the eight mental health conditions, 2,002 were standardized and rated by small groups of consumers and experts. Expert ratings of item relevance tended to correlate moderately with consumer ratings, with variation across conditions. An algorithm was used to generate final item pools ranging from 45 to 75 items., Conclusion: The study successfully applied a systematic process to select items for assessing a range of mental disorders. This process for item selection may be applied to additional mental and physical health conditions. The calibration of the present item pools into final item banks will enable the development of flexible measures to assess risk of mental health problems, although more effectively accounting for comorbidity., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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7. A systematic review and evaluation of measures for suicidal ideation and behaviors in population-based research.
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Batterham PJ, Ftanou M, Pirkis J, Brewer JL, Mackinnon AJ, Beautrais A, Fairweather-Schmidt AK, and Christensen H
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- Depression psychology, Humans, Psychometrics, Research Design, Residence Characteristics, Self Report, Surveys and Questionnaires, Suicidal Ideation, Suicide psychology
- Abstract
The use of measures of suicidal ideation and behavior with sound measurement properties is critical in identifying people most at risk of suicide. In particular, brief self-report measures of suicidal ideation and behaviors are needed for use in large-scale population-based research and in the development and evaluation of suicide prevention programs in the community. This review aimed to identify and recommend psychometrically sound self-report measures of suicidal ideation and behaviors that could be used in population-based research of adults. To identify existing self-report measures for adult use, a systematic search was conducted using MEDLINE (Medical Literature Analysis and Retrieval System Online) and PsycINFO (Psychological Information Database) databases. Abstracts, reference lists, and previous review papers were screened. Once measures were identified, we used a hierarchical criterion-based approach to assess their utility, psychometric properties, and appropriateness for population-based research. Nineteen measures were evaluated against 6 criteria. Three brief measures that met all criteria of the evaluation and demonstrated adequate psychometric properties were the Depressive Symptom Index Suicidality Subscale (DSI-SS), Suicidal Behaviors Questionnaire-Revised (SBQ-R), and Suicidal Ideation Attributes Scale (SIDAS). None of the comprehensive measures met all criteria for use in population-based studies, due to financial costs imposed on use, although the Beck Scale for Suicide Ideation (BSSI) and the Adult Suicidal Ideation Questionnaire (ASIQ) had considerable evidence of psychometric robustness. Suicide researchers are encouraged to further establish the validity of scores on these measures across diverse adult populations., ((c) 2015 APA, all rights reserved).)
- Published
- 2015
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8. Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults.
- Author
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Ali A, Herndon DN, Mamachen A, Hasan S, Andersen CR, Grogans RJ, Brewer JL, Lee JO, Heffernan J, Suman OE, and Finnerty CC
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- Adrenergic beta-Antagonists pharmacology, Adrenergic beta-Antagonists therapeutic use, Adult, Burns surgery, Cohort Studies, Female, Humans, Male, Middle Aged, Propranolol pharmacology, Blood Loss, Surgical prevention & control, Burns drug therapy, Propranolol therapeutic use, Severity of Illness Index, Skin Transplantation adverse effects, Wound Healing drug effects
- Abstract
Introduction: Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults., Methods: Sixty-nine adult patients with burns covering ≥ 30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge., Results: Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group (P < 0.05). The average number of days between skin grafting procedures was also lower in propranolol patients (10 ± 5 days) than in control patients (17 ± 12 days; P = 0.02), indicative of a faster donor site healing time in the propranolol group. Packed red blood cell infusion was similar between groups (control 5.3 ± 5.4 units vs. propranolol 4.4 ± 3.1 units, P = 0.89). Propranolol was associated with a 5 to 7% improvement in perioperative hematocrit during grafting procedures of 4,000 to 16,000 cm(2) compared to control (P = 0.002)., Conclusions: Administration of propranolol during the acute hospitalization period diminishes blood loss during skin grafting procedures and markedly improves wound healing in severely burned adults. As burn patients require serial surgical interventions for motor and cosmetic repair, restricting blood loss during operative intervention is optimal.
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- 2015
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9. A systematic review of help-seeking interventions for depression, anxiety and general psychological distress.
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Gulliver A, Griffiths KM, Christensen H, and Brewer JL
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- Anxiety Disorders therapy, Depressive Disorder therapy, Humans, Mental Health, Psychotherapy, Stress, Psychological therapy, Anxiety Disorders psychology, Depressive Disorder psychology, Health Literacy, Patient Acceptance of Health Care, Stress, Psychological psychology
- Abstract
Background: Depression and anxiety are treatable disorders, yet many people do not seek professional help. Interventions designed to improve help-seeking attitudes and increase help-seeking intentions and behaviour have been evaluated in recent times. However, there have been no systematic reviews of the efficacy or effectiveness of these interventions in promoting help-seeking. Therefore, this paper reports a systematic review of published randomised controlled trials targeting help-seeking attitudes, intentions or behaviours for depression, anxiety, and general psychological distress., Methods: Studies were identified through searches of PubMed, PsycInfo, and the Cochrane database in November 2011. Studies were included if they included a randomised controlled trial of at least one intervention targeting help-seeking for depression or anxiety or general psychological distress, and contained extractable data on help-seeking attitudes or intentions or behaviour. Studies were excluded if they focused on problems or conditions other than the target (e.g., substance use, eating disorder)., Results: Six published studies of randomised controlled trials investigating eight different interventions for help-seeking were identified. The majority of trials targeted young adults. Mental health literacy content was effective (d = .12 to .53) in improving help-seeking attitudes in the majority of studies at post-intervention, but had no effect on help-seeking behaviour (d = -.01, .02). There was less evidence for other intervention types such as efforts to destigmatise or provide help-seeking source information., Conclusions: Mental health literacy interventions are a promising method for promoting positive help-seeking attitudes, but there is no evidence that it leads to help-seeking behaviour. Further research investigating the effects of interventions on attitudes, intentions, and behaviour is required.
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- 2012
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10. Impact of the lectin chaperone calnexin on the stress response, virulence and proteolytic secretome of the fungal pathogen Aspergillus fumigatus.
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Powers-Fletcher MV, Jambunathan K, Brewer JL, Krishnan K, Feng X, Galande AK, and Askew DS
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- Animals, Calnexin genetics, Cations, Culture Media pharmacology, DNA Primers genetics, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress, Female, Fungal Proteins genetics, Gene Expression Regulation, Fungal, Immunosuppressive Agents therapeutic use, Mice, Polymerase Chain Reaction methods, Protein Folding, Temperature, Virulence, Aspergillus fumigatus metabolism, Calnexin chemistry, Calnexin physiology, Fungal Proteins physiology, Lectins chemistry
- Abstract
Calnexin is a membrane-bound lectin chaperone in the endoplasmic reticulum (ER) that is part of a quality control system that promotes the accurate folding of glycoproteins entering the secretory pathway. We have previously shown that ER homeostasis is important for virulence of the human fungal pathogen Aspergillus fumigatus, but the contribution of calnexin has not been explored. Here, we determined the extent to which A. fumigatus relies on calnexin for growth under conditions of environmental stress and for virulence. The calnexin gene, clxA, was deleted from A. fumigatus and complemented by reconstitution with the wild type gene. Loss of clxA altered the proteolytic secretome of the fungus, but had no impact on growth rates in either minimal or complex media at 37°C. However, the ΔclxA mutant was growth impaired at temperatures above 42°C and was hypersensitive to acute ER stress caused by the reducing agent dithiothreitol. In contrast to wild type A. fumigatus, ΔclxA hyphae were unable to grow when transferred to starvation medium. In addition, depleting the medium of cations by chelation prevented ΔclxA from sustaining polarized hyphal growth, resulting in blunted hyphae with irregular morphology. Despite these abnormal stress responses, the ΔclxA mutant remained virulent in two immunologically distinct models of invasive aspergillosis. These findings demonstrate that calnexin functions are needed for growth under conditions of thermal, ER and nutrient stress, but are dispensable for surviving the stresses encountered in the host environment.
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- 2011
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11. Safety assessment of a home-based telecare system for adults with developmental disabilities in Indiana: a multi-stakeholder perspective.
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Brewer JL, Taber-Doughty T, and Kubik S
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- Adult, Aged, Consumer Behavior, Home Care Services organization & administration, Humans, Indiana, Middle Aged, Quality of Health Care organization & administration, Young Adult, Caregivers psychology, Developmental Disabilities nursing, Home Care Services standards, Night Care standards, Quality of Health Care standards, Telemedicine standards
- Abstract
We investigated the perceptions of people about the safety, security and privacy of a telecare monitoring system for adults with developmental disabilities living in residential settings. The telecare system was used by remote caregivers overnight, when staff were not present in the homes. We surveyed 127 people from different stakeholder groups in the state of Indiana. The people surveyed included those with knowledge or experience of telecare, and those without. The stakeholders were clients, their advocates, service provider administrators and independent case coordinators. The responses in each category for every group were positive except one: only 4 of the 11 telecare case coordinators agreed that the telecare system provided a secure environment. Overall, the telecare system was perceived to be as safe, secure and private as the conventional alternative of having staff in the home.
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- 2010
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12. An information technology emphasis in biomedical informatics education.
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Kane MD and Brewer JL
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- Biotechnology organization & administration, Curriculum, Indiana, Biomedical Engineering education, Biomedical Engineering organization & administration, Biotechnology education, Computational Biology education, Computational Biology organization & administration, Education, Professional organization & administration, Universities organization & administration
- Abstract
Unprecedented growth in the interdisciplinary domain of biomedical informatics reflects the recent advancements in genomic sequence availability, high-content biotechnology screening systems, as well as the expectations of computational biology to command a leading role in drug discovery and disease characterization. These forces have moved much of life sciences research almost completely into the computational domain. Importantly, educational training in biomedical informatics has been limited to students enrolled in the life sciences curricula, yet much of the skills needed to succeed in biomedical informatics involve or augment training in information technology curricula. This manuscript describes the methods and rationale for training students enrolled in information technology curricula in the field of biomedical informatics, which augments the existing information technology curriculum and provides training on specific subjects in Biomedical Informatics not emphasized in bioinformatics courses offered in life science programs, and does not require prerequisite courses in the life sciences.
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- 2007
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13. Familiar other-race faces show normal holistic processing and are robust to perceptual stress.
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McKone E, Brewer JL, MacPherson S, Rhodes G, and Hayward WG
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- Adolescent, Adult, Animals, Discrimination, Psychological, Dogs, Female, Humans, Male, Memory, Asian People psychology, Face, Recognition, Psychology, Visual Perception, White People psychology
- Abstract
Other-race individuals are remembered more poorly and receive less holistic/configural processing than same-race individuals, at least when faces are novel. Here, we examine the amelioration of these effects with familiarity, using distinctiveness-matched Caucasian and Asian stimulus sets. We confirmed a cross-race deficit for upright faces following a single encoding trial, which disappeared rapidly with practice on a small set of other-race 'friends' and did not re-emerge when perceptual processing was put under stress (presentation in the periphery). We also examined holistic/configural processing for familiarised faces using the peripheral inversion effect (McKone, 2004 Journal of Experimental Psychology: Learning, Memory, and Cognition 30 181 - 197). A test for faces and nonface objects (dogs) confirmed the validity of this technique as providing a direct measure of holistic processing; we then showed that, after 1 h of training, holistic processing was as strong for other-race as same-race faces. We conclude that practice with other-race individuals can rapidly engage normal face-processing mechanisms.
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- 2007
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14. Disruption of a locus encoding a nucleolar zinc finger protein decreases tachyzoite-to-bradyzoite differentiation in Toxoplasma gondii.
- Author
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Vanchinathan P, Brewer JL, Harb OS, Boothroyd JC, and Singh U
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- Amino Acid Sequence, Animals, Cell Differentiation genetics, Cell Nucleolus chemistry, Cell Nucleolus metabolism, Genes, Protozoan, Molecular Sequence Data, Mutagenesis, Insertional, Nuclear Proteins analysis, Nuclear Proteins metabolism, Protein Transport, Protozoan Proteins analysis, Protozoan Proteins metabolism, Transcription Initiation Site, Transcription, Genetic, Zinc Fingers, Gene Expression Regulation, Developmental, Nuclear Proteins genetics, Protozoan Proteins genetics, Toxoplasma genetics, Toxoplasma growth & development
- Abstract
During its life cycle in intermediate hosts, Toxoplasma gondii exists in two interconverting developmental stages: tachyzoites and bradyzoites. This interconversion is essential for the survival and pathogenicity of the parasite, but little is known about the genetic mechanisms that control this process. We have previously generated tachyzoite-to-bradyzoite differentiation (Tbd(-)) mutants using chemical mutagenesis and a green fluorescent protein-based selection strategy. The genetic loci responsible for the Tbd(-) phenotype, however, could not be identified. We have now used an insertional mutagenesis strategy to generate two differentiation mutants: TBD-5 and TBD-6 that switch to bradyzoites at 10 and 50% of wild-type levels, respectively. In TBD-6 there is a single insertion of the mutagenesis vector 164 bp upstream of the transcription start site of a gene encoding a zinc finger protein (ZFP1). Disruption of this locus in wild-type parasites reproduces the decreased stage conversion phenotype. ZFP1 is targeted to the parasite nucleolus by CCHC motifs and significantly altered expression levels are toxic to the parasites. This represents the first identification of a gene necessary for efficient conversion of tachyzoites to bradyzoites.
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- 2005
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15. Bladder cancer stage and outcome by array-based comparative genomic hybridization.
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Blaveri E, Brewer JL, Roydasgupta R, Fridlyand J, DeVries S, Koppie T, Pejavar S, Mehta K, Carroll P, Simko JP, and Waldman FM
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- Chromosome Mapping, Chromosomes, Artificial, Bacterial, Cluster Analysis, DNA chemistry, DNA metabolism, Disease Progression, Gene Deletion, Gene Expression Profiling, Genetic Linkage, Humans, Image Processing, Computer-Assisted, Multivariate Analysis, Oligonucleotide Array Sequence Analysis, Phenotype, Prognosis, Proportional Hazards Models, Time Factors, Treatment Outcome, Gene Expression Regulation, Neoplastic, Genome, Nucleic Acid Hybridization, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms genetics
- Abstract
Purpose: Bladder carcinogenesis is believed to follow alternative pathways of disease progression driven by an accumulation of genetic alterations. The purpose of this study was to evaluate associations between measures of genomic instability and bladder cancer clinical phenotype., Experimental Design: Genome-wide copy number profiles were obtained for 98 bladder tumors of diverse stages (29 pT(a), 14 pT1, 55 pT(2-4)) and grades (21 low-grade and 8 high-grade superficial tumors) by array-based comparative genomic hybridization (CGH). Each array contained 2,464 bacterial artificial chromosome and P1 clones, providing an average resolution of 1.5 Mb across the genome. A total of 54 muscle-invasive cases had follow-up information available. Overall outcome analysis was done for patients with muscle-invasive tumors having "good" (alive >2 years) versus "bad" (dead in <2 years) prognosis., Results: Array CGH analysis showed significant increases in copy number alterations and genomic instability with increasing stage and with outcome. The fraction of genome altered (FGA) was significantly different between tumors of different stages (pT(a) versus pT1, P = 0.0003; pT(a) versus pT(2-4), P = 0.02; and pT1 versus pT(2-4), P = 0.03). Individual clones that differed significantly between different tumor stages were identified after adjustment for multiple comparisons (false discovery rate < 0.05). For muscle-invasive tumors, the FGA was associated with patient outcome (bad versus good prognosis patients, P = 0.002) and was identified as the only independent predictor of overall outcome based on a multivariate Cox proportional hazards method. Unsupervised hierarchical clustering separated "good" and "bad" prognosis muscle-invasive tumors into clusters that showed significant association with FGA and survival (Kaplan-Meier, P = 0.019). Supervised tumor classification (prediction analysis for microarrays) had a 71% classification success rate based on 102 unique clones., Conclusions: Array-based CGH identified quantitative and qualitative differences in DNA copy number alterations at high resolution according to tumor stage and grade. Fraction genome altered was associated with worse outcome in muscle-invasive tumors, independent of other clinicopathologic parameters. Measures of genomic instability add independent power to outcome prediction of bladder tumors.
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- 2005
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16. Cre-mediated site-specific recombination in zebrafish embryos.
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Thummel R, Burket CT, Brewer JL, Sarras MP Jr, Li L, Perry M, McDermott JP, Sauer B, Hyde DR, and Godwin AR
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- Animals, Animals, Genetically Modified, Embryo, Nonmammalian physiology, Genes, Reporter, HSP70 Heat-Shock Proteins genetics, Mosaicism, Recombinant Fusion Proteins genetics, Zebrafish genetics, beta-Galactosidase genetics, Integrases, Mutagenesis, Site-Directed, Recombination, Genetic, Zebrafish embryology
- Abstract
Cre-mediated site-specific recombination has become an invaluable tool for manipulation of the murine genome. The ability to conditionally activate gene expression or to generate chromosomal alterations with this same tool would greatly enhance zebrafish genetics. This study demonstrates that the HSP70 promoter can be used to inducibly control expression of an enhanced green fluorescent protein (EGFP) -Cre fusion protein. The EGFP-Cre fusion protein is capable of promoting recombination between lox sites in injected plasmids or in stably inherited transgenes as early as 2 hr post-heat shock induction. Finally, the levels of Cre expression achieved in a transgenic fish line carrying the HSP70-EGFP-cre transgene are compatible with viability and both male and female transgenic fish are fertile subsequent to induction of EGFP-Cre expression. Hence, our data suggests that Cre-mediated recombination is a viable means of manipulating gene expression in zebrafish., ((c) 2005 Wiley-Liss, Inc.)
- Published
- 2005
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17. An improved methodology to detect human T cell receptor beta variable family gene expression patterns.
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Brewer JL and Ericson SG
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- DNA Primers, Fluorometry methods, Genetic Variation, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells metabolism, Humans, Polymerase Chain Reaction methods, RNA, Messenger biosynthesis, Gene Expression Profiling methods, Multigene Family, Receptors, Antigen, T-Cell, alpha-beta biosynthesis, Receptors, Antigen, T-Cell, alpha-beta genetics
- Abstract
Comprehensive gene expression analysis of the T cell receptor repertoire of an individual can be very useful in evaluating the immune response in a variety of conditions. Antibody-based analysis methods can detect approximately 60% of the human T cell receptor beta variable (TCRBV) proteins, while gene expression analysis, primarily through employment of the polymerase chain reaction (PCR), has had somewhat greater success in the detection of additional TCRBV families. Many of these previous PCR methods, however, have been unable to detect all 91 alleles of the human TCRBV genes. This is primarily due to either deficiencies in the amplification of all of the variable beta families, subfamilies, and alleles, or the prior lack of a systematic classification of the TCR variable family gene segment sequences. We describe here a real-time reverse transcription polymerase chain reaction-based method, which allows efficient automation and integration of amplification, detection, and analysis with sequence-specific detection of all T cell receptor beta variable gene families, subfamilies, and alleles. This method, which in itself contributes significant improvements over existing technologies through its comprehensiveness and efficiency, also functions independently of variables such as sample source and sample processing and has the ability to run on multiple real-time PCR platforms, affording one the implementation of personal preferences.
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- 2005
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18. Bladder cancer outcome and subtype classification by gene expression.
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Blaveri E, Simko JP, Korkola JE, Brewer JL, Baehner F, Mehta K, Devries S, Koppie T, Pejavar S, Carroll P, and Waldman FM
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- Aged, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Carcinoma, Transitional Cell genetics, Carcinoma, Transitional Cell metabolism, Carcinoma, Transitional Cell pathology, Cell Line, Tumor, Cluster Analysis, Cyclin A analysis, Cyclin A2, Female, Gene Expression Regulation, Neoplastic genetics, HL-60 Cells, Humans, Immunohistochemistry, Male, Neoplasm Staging, Oligonucleotide Array Sequence Analysis methods, Parathyroid Hormone-Related Protein analysis, Prognosis, Urinary Bladder Neoplasms classification, Urinary Bladder Neoplasms metabolism, Gene Expression Profiling, Urinary Bladder Neoplasms genetics
- Abstract
Models of bladder tumor progression have suggested that genetic alterations may determine both phenotype and clinical course. We have applied expression microarray analysis to a divergent set of bladder tumors to further elucidate the course of disease progression and to classify tumors into more homogeneous and clinically relevant subgroups. cDNA microarrays containing 10,368 human gene elements were used to characterize the global gene expression patterns in 80 bladder tumors, 9 bladder cancer cell lines, and 3 normal bladder samples. Robust statistical approaches accounting for the multiple testing problem were used to identify differentially expressed genes. Unsupervised hierarchical clustering successfully separated the samples into two subgroups containing superficial (pT(a) and pT(1)) versus muscle-invasive (pT(2)-pT(4)) tumors. Supervised classification had a 90.5% success rate separating superficial from muscle-invasive tumors based on a limited subset of genes. Tumors could also be classified into transitional versus squamous subtypes (89% success rate) and good versus bad prognosis (78% success rate). The performance of our stage classifiers was confirmed in silico using data from an independent tumor set. Validation of differential expression was done using immunohistochemistry on tissue microarrays for cathepsin E, cyclin A2, and parathyroid hormone-related protein. Genes driving the separation between tumor subsets may prove to be important biomarkers for bladder cancer development and progression and eventually candidates for therapeutic targeting.
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- 2005
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19. Toxoplasma gondii asexual development: identification of developmentally regulated genes and distinct patterns of gene expression.
- Author
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Cleary MD, Singh U, Blader IJ, Brewer JL, and Boothroyd JC
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- Animals, Enzymes genetics, Expressed Sequence Tags, Gene Expression Profiling, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Protozoan Proteins genetics, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Protozoan genetics, RNA, Protozoan metabolism, Toxoplasma metabolism, Genes, Protozoan, Toxoplasma genetics, Toxoplasma growth & development
- Abstract
Asexual development in Toxoplasma gondii is a vital aspect of the parasite's life cycle, allowing transmission and avoidance of the host immune response. Differentiation of rapidly dividing tachyzoites into slowly growing, encysted bradyzoites involves significant changes in both physiology and morphology. We generated microarrays of approximately 4,400 Toxoplasma cDNAs, representing a minimum of approximately 600 genes (based on partial sequencing), and used these microarrays to study changes in transcript levels during tachyzoite-to-bradyzoite differentiation. This approach has allowed us to (i) determine expression profiles of previously described developmentally regulated genes, (ii) identify novel developmentally regulated genes, and (iii) identify distinct classes of genes based on the timing and magnitude of changes in transcript levels. Whereas microarray analysis typically involves comparisons of mRNA levels at different time points, we have developed a method to measure relative transcript abundance between genes at a given time point. This method was used to determine transcript levels in parasites prior to differentiation and to further classify bradyzoite-induced genes, thus allowing a more comprehensive view of changes in gene expression than is provided by standard expression profiles. Newly identified developmentally regulated genes include putative surface proteins (a SAG1-related protein, SRS9, and a mucin-domain containing protein), regulatory and metabolic enzymes (methionine aminopeptidase, oligopeptidase, aminotransferase, and glucose-6-phosphate dehydrogenase homologues), and a subset of genes encoding secretory organelle proteins (MIC1, ROP1, ROP2, ROP4, GRA1, GRA5, and GRA8). This analysis permits the first in-depth look at changes in gene expression during development of this complex protozoan parasite.
- Published
- 2002
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20. Genetic analysis of tachyzoite to bradyzoite differentiation mutants in Toxoplasma gondii reveals a hierarchy of gene induction.
- Author
-
Singh U, Brewer JL, and Boothroyd JC
- Subjects
- Animals, Antiprotozoal Agents pharmacology, Atovaquone, Cell Differentiation genetics, Gene Expression Profiling, Genes, Protozoan, Genes, Reporter, Green Fluorescent Proteins, Luminescent Proteins biosynthesis, Luminescent Proteins genetics, Mice, Mutagenesis, Naphthoquinones pharmacology, Oligonucleotide Array Sequence Analysis, Phenotype, Protozoan Proteins biosynthesis, Protozoan Proteins genetics, Recombinant Fusion Proteins biosynthesis, Recombinant Fusion Proteins genetics, Selection, Genetic, Toxoplasma drug effects, Toxoplasma growth & development, Toxoplasmosis, Animal parasitology, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Developmental, Toxoplasma genetics
- Abstract
Developmental switching in Toxoplasma gondii, from the virulent tachyzoite to the relatively quiescent bradyzoite stage, is responsible for disease propagation and reactivation. We have generated tachyzoite to bradyzoite differentiation (Tbd-) mutants in T. gondii and used these in combination with a cDNA microarray to identify developmental pathways in bradyzoite formation. Four independently generated Tbd- mutants were analysed and had defects in bradyzoite development in response to multiple bradyzoite-inducing conditions, a stable phenotype after in vivo passages and a markedly reduced brain cyst burden in a murine model of chronic infection. Transcriptional profiles of mutant and wild-type parasites, growing under bradyzoite conditions, revealed a hierarchy of developmentally regulated genes, including many bradyzoite-induced genes whose transcripts were reduced in all mutants. A set of non-developmentally regulated genes whose transcripts were less abundant in Tbd- mutants were also identified. These may represent genes that mediate downstream effects and/or whose expression is dependent on the same transcription factors as the bradyzoite-induced set. Using these data, we have generated a model of transcription regulation during bradyzoite development in T. gondii. Our approach shows the utility of this system as a model to study developmental biology in single-celled eukaryotes including protozoa and fungi.
- Published
- 2002
- Full Text
- View/download PDF
21. Prenatal care and HIV screening.
- Author
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Kaunitz AM, Brewer JL, Paryani SG, deSausure L, Sanchez-Ramos L, and Harrington P
- Subjects
- Female, Humans, Mass Screening, Pregnancy, HIV Seropositivity diagnosis, Pregnancy Complications, Infectious diagnosis, Pregnant Women, Prenatal Care methods
- Published
- 1987
22. Nephroblastoma with pulmonary metastases in a guanaco.
- Author
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Dietrich JG and Brewer JL
- Subjects
- Animals, Humans, Kidney Neoplasms pathology, Lung Neoplasms pathology, Lung Neoplasms secondary, Male, Wilms Tumor pathology, Wilms Tumor secondary, Artiodactyla, Camelids, New World, Kidney Neoplasms veterinary, Lung Neoplasms veterinary, Wilms Tumor veterinary
- Published
- 1988
- Full Text
- View/download PDF
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