1,278 research outputs found

    A novel DRD2 single-nucleotide polymorphism associated with schizophrenia predicts age of onset: HapMap tag-sincle-nucleotide polymorphism analysis

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    Background: Dopamine D2 receptor (DRD2) is thought to be critical in regulating the dopaminergic pathway in the brain which is known to be important in the aetiology of schizophrenia. It is therefore not surprising that most antipsychotic medication acts on the Dopamine D2 receptor. DRD2 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and DRD2 polymorphisms have been associated with reduced brain expression. We have previously identified a genetic variant in DRD2, rs6277 to be strongly implicated in schizophrenia susceptibility. Methods: To identity new associations in the DRD2 gene with disease status and clinical severity, we genotyped seven single nucleotide polymorphisms (SNPs) in DRD2 using a multiplex mass spectrometry method. SNPs were chosen using a haplotype block-based gene-tagging approach so the entire DRD2 gene was represented. Results: One polymorphism rs2734839 was found to be significantly associated with schizophrenia as well as late onset age. Individuals carrying the genetic variation were more than twice as likely to have schizophrenia compared to controls. Conclusions: Our results suggest that DRD2 genetic variation is a good indicator for schizophrenia risk and may also be used as a predictor age of onset

    A Comparison of Maternal Attachment between American Adolescent and Adult Mothers of Preschoolers

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    American adolescent mothers have been viewed as less effective parents than adult mothers. The socioeconomic disadvantages of adolescent mothers should be taken into account. The objectives of this study were to compare maternal attachment between adolescent and adult mothers of preschoolers and to examine changes of adolescents’ maternal attachment over time. A secondary analysis of data from a larger study of maternal employment and low birth weight infant outcomes were used. Data were collected through home visits using structured questionnaires at two different time points. Forty-three pairs of adolescent and adult mothers who could be matched on family structure, maternal race, and child’s gestational status were compared on maternal attachment. The 7-item Attachment subscale of the Parenting Stress Index was used to measure maternal attachment. Results revealed that the adolescent mothers were not less attached to their preschoolers than the adults. This held true when important confounding factors were taken into account using multiple regression

    Characteristics of Aboriginal Injecting Drug Users in Sydney, Australia: Prison History, Hepatitis C Status and Drug Treatment Experiences

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    Australian Aboriginals are overrepresented in prisons and tend to be overrepresented in studies of injecting drug users (IDU). The aim of this study was to examine differences between Aboriginal and non-Aboriginal IDUs in terms of gender, prison history and hepatitis C status and testing. Secondary analyses were conducted on data from three cross-sectional studies of IDUs. These studies employed similar methodologies, with recruitment being through needle and syringe programs, methadone clinics, snowballing and street intercepts. All studies were coordinated through the National Drug and Alcohol Research Centre. Aboriginal people were overrepresented in all studies, were more likely to have been incarcerated and to report heroin as their drug of choice than non-Aboriginal IDUs. Females tended to be overrepresented among Aboriginal IDUs, were more likely to have been incarcerated and had a longer period of time since their last hepatitis C test than non-Aboriginal female IDUs. Aboriginal people are overrepresented among IDUs in Sydney. Given their greater risk of incarceration, particularly among females, Aboriginal IDUs were at greater risk of hepatitis C exposure than non-Aboriginal IDUs. The prison setting provides an opportunity to promote drug treatment and hepatitis C testing, though more needs to be done to reduce drug use and incarceration

    Initiation to heroin injecting among heroin users in Sydney, Australia: cross sectional survey

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    BACKGROUND: Heroin injection is associated with health and social problems including hepatitis C virus (HCV) transmission. Few studies have examined the circumstances surrounding initiation to heroin injecting, especially current users initiating others. The current study aimed to examine the age of first heroin use and injection; administration route of first heroin use; relationship to initiator; the initiation of others among a group of heroin users; and to examine these factors in relation to HCV status and risk. METHOD: Heroin users in Sydney were recruited through needle and syringe programs, a methadone clinic and snowballing. Participants were interviewed about their own initiation to heroin use, blood-borne virus risk and knowledge, and whether they had initiated others to heroin injecting. Information on HCV status was collected via self-report. Data was analysed using univariate and multivariate statistical techniques for Normally distributed continuous and categorical data. RESULTS: The study recruited 399 heroin users, with a mean age of 31 years, 63% were male, 77% reported heroin as their primary drug and 59% were HCV positive (self-report). Mean age at first heroin use and injection was 19 and 21 years, respectively. The majority of heroin users commenced heroin use via injecting (65%), younger users (<25 years, 25–30 years) were less likely than older users (>30 years) to commence heroin use parenterally. Participants were initiated to injection mainly by friends (63%). Thirty-seven percent reported initiating others to heroin injection, but few factors were related to this behaviour. Those with longer heroin using careers were more likely to report initiating others to heroin injection, but were no more likely to have done so in the preceding 12 months. Participants who had initiated others were more likely to have shared injecting equipment (12 vs 23%), but were no more likely to be HCV positive (self-report) than those who did not. CONCLUSION: Interventions to prevent heroin users initiating others to injecting are necessary. Peer groups may be well positioned to implement such interventions

    Pneumococcal and influenza immunization in asplenic persons: a retrospective population-based cohort study 1990-2002

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    <p>Abstract</p> <p>Background</p> <p>Splenectomy is associated with increased risk for bacteremia, due to impaired clearance of bloodborne agents and to altered phagocytosis and humoral immunity. We conducted a retrospective cohort study of patients at risk for splenectomy for a 13-year period to determine immunization coverage, and outcomes of those with and without splenectomy, and with or without receipt of influenza or pneumococcal vaccine.</p> <p>Methods</p> <p>Data were extracted from the provincial Medical Services Insurance database for insured services rendered by a physician for 1990-2002, and from the Vital Statistics Death database. The eligible cohort was selected based on diagnostic codes for hematologic conditions for which splenectomy might be considered, such as immune thrombocytopenia. Each patient was followed longitudinally from the date of first diagnosis until 31Dec2002, or death, or relocation out-of province. In addition, persons with splenectomy and no hematologic condition were identified and followed for 6 months post-surgery. Infectious illness rates per 100 person-years of observation and death rates were calculated with and without splenectomy. Death rates were determined using splenectomy status as a time-dependent covariate. The relationship between splenectomy and death according to immunization status was examined using Cox proportional hazard ratios.</p> <p>Results</p> <p>Of 38,812 persons in the cohort 427 subjects with a hematologic diagnosis had splenectomy and another 452 subjects without a hematologic diagnosis had this surgery. 72% were > 18 years of age. Pneumococcal immunization was recorded in 16.5% of asplenic patients overall, and was not associated with reduced risk of death in these persons (adjusted Hazard Ratio [HR] = 1.07, 95% CI 0.70 - 1.65). Influenza immunization was recorded in 53.1% of asplenic patients overall, and was associated with reduced risk of death (adjusted HR = 0.46, 0.33-0.62). No pneumococcal or influenza immunization was recorded in patients with a hematologic diagnosis without splenectomy. Infectious illness visits were higher among all patients who had a splenectomy than among those without a splenectomy (151 visits/100 person-years of observation in the post-splenectomy period vs. 120 visits/100 person-years; p < 0.0001).</p> <p>Conclusions</p> <p>In asplenic patients, influenza immunization is associated with a 54% reduced risk of death compared to unimmunized asplenic persons; no reduction in risk was demonstrated with (polysaccharide) pneumococcal vaccine. Vaccine coverage in the entire cohort was less than routinely recommended. Improved delivery of infection prevention programs to this population is warranted. Conjugate pneumococcal vaccines should be urgently studied in this immunocompromised population.</p

    Major Depression among methamphetamine users entering drug treatment programs

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    Objective: To determine the prevalence of major depression among people entering treatment for methamphetamine use. Design, setting and participants: The study was a cross-sectional survey involving 41 specialised drug and alcohol treatment agencies in Brisbane and Sydney. Services provided by these agencies included residential rehabilitation, detoxification and counselling. Participants were 400 people entering treatment for methamphetamine use who were recruited from participating treatment agencies between January 2006 and November 2007. Participants underwent a structured, face-to-face, 1.5-hour interview. Assessment instruments included the Composite International Diagnostic Interview and the Short Form 12. Main outcome measure: Diagnosis of a major depressive episode in the year prior to the study. Results: The prevalence of major depression in the year prior to the study was 40% (95% CI, 35%-44%). A noteworthy post-hoc observation was that a further 44% of participants met the symptom criteria for major depression but were excluded from a diagnosis because their symptoms were better accounted for by psychoactive substance use. Both major depression and these latter cases of "substance-induced depression" were associated with severe symptoms of depression, high levels of disability and suicidal ideation. Conclusion: Most people entering treatment programs for methamphetamine use have levels of depression that require clinical management. Making a diagnosis of major depression in the context of heavy methamphetamine use is problematic because of substance-induced symptoms of depression

    Cell culture manufacturing of accelerated projects - Lessons from life in the fast lane

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    The possibility of promising molecules receiving Breakthrough Therapy Designation (BTD) early in their clinical lifecycle encourages accelerated development strategies to decrease approval timelines. The speed that these projects move through the pipeline has required Genentech’s manufacturing organization to push the limits of their manufacturing flexibility in order to support a streamlined approach to scale-up. Recent accelerated development product manufacturing presented several new operational, logistical and technical challenges which required creative solutions to overcome, in order to achieve tight in-process control while maintaining agility. This poster will discuss the lessons learned by the manufacturing site while executing that Cell Culture manufacturing campaign, including The benefits and challenges associated with: Process qualification with limited small scale data Operating within a narrow design space Leveraging a clinical facility for process qualification activities Supporting new strategies in an existing facilit
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