Gene transfer and expression of a non-viral polycation-based vector in CD4(+) cells

CD4-selective targeting of an antibody-polycation-DNA complex was investigated The complex was synthesized with the anti-CD4 monoclonal antibody B-F5, polylysine(268) (pLL) and either the pGL3 control vector containing the luciferase reporter gene or the pGeneGrip vector containing the green fluorescent protein (GFP) gene. B-F5-pLL-DNA complexes inhibited the binding of I-125-B-F5 to CD4(+) Jurkat cells, while complexes synthesised either without B-F5 or using a non-specific mouse IgG1 antibody had little or no effect Expression of the luciferase reporter gene was achieved in Jurkat cells using the B-F5-pLL-pGL3 complex and was enhanced in the presence of PMA. Negligible luciferase activity was defected with the non-specific antibody complex in Jurkat cells or with the B-F5-pLL-pGL3 complex in the CD4(-) K-562 cells. Using complexes synthesised with the pGeneGrip vector, the transfection efficiency in Jurkat and K-562 cells was examined using confocal microscopy. More than 95% of Jurkat cells expressed GFP and the level of this expression was markedly enhanced by PMA. Negligible GFP expression was seen in K-562 cells or when B-F5 was replaced by a nonspecific antibody. Using flow cytometry, fluorescein-labelled complex showed specific targeting to CD4(+) cells in a mixed cell population from human peripheral blood. These studies demonstrate the selective transfection of CD4(+) T-lymphoid cells using a polycation-based gene delivery system. The complex may provide a means of delivering anti-HIV gene therapies to CD4(+) cells in vivo.

Gene and genotypic diversity of Phytophthora cinnamomi in South Africa and Australia revealed by DNA polymorphisms

Phytophthora cinnamomi isolates from South Africa and Australia were compared to assess genetic differentiation between the two populations. These two populations were analysed for levels of phenotypic diversity using random amplified polymorphic DNAs (RAPDs) and gene and genotypic diversity using restriction fragment length polymorphisms (RFLPs). Sixteen RAPD markers from four decanucleotide Operon primers and 34 RFLP alleles from 15 putative loci were used. A few isolates from Papua New Guinea known to posses alleles different from Australian isolates were also included for comparative purposes. South African and Australian P. cinnamomi populations were almost identical with an extremely low level of genetic distance between them (D-m = 0.003). Common features for the two populations include shared alleles, low levels of phenotypic/genotypic diversity, high clonality, and low observed and expected levels of heterozygosity. Furthermore, relatively high levels of genetic differentiation between mating type populations (D-m South Africa = 0.020 and D-m Australia = 0.025 respectively), negative fixation indices, and significant deviations from Hardy-Weinberg equilibrium, all provided evidence for the lack of frequent sexual reproduction in both populations. The data strongly suggest that both the South African and Australian P. cinnamomi populations are introduced.

Who fails to complete tuberculosis treatment? Temporal trends and risk factors for treatment interruption in a community-based directly observed therapy programme in a rural district of South Africa

SETTING: Hlabisa Tuberculosis Programme, Hlabisa, South Africa. OBJECTIVE: To determine trends in and risk factors for interruption of tuberculosis treatment. METHODS: Data were extracted from the control programme database starting in 1991. Temporal trends in treatment interruption are described; independent risk factors for treatment interruption were determined with a multiple logistic regression model, and Kaplan-Meier survival curves for treatment interruption were constructed for patients treated in 1994-1995. RESULTS: Overall 629 of 3610 surviving patients (17%) failed to complete treatment; this proportion increased from 11% (n = 79) in 1991/1992 to 22% (n = 201) in 1996. Independent risk factors for treatment interruption were diagnosis between 1994-1996 compared with 1991-1393 (odds ratio [OR] 1.9, 95% confidence interval [CT] 1.6-2.4); human immunodeficiency virus (HIV) positivity compared with HIV negativity (OR 1.8, 95% CI 1.4-2.4); supervised by village clinic compared with community health worker (OR 1.9, 95% CI 1.4-2.6); and male versus female sex (OR 1.3, 95% CI 1.1-1.6). Few patients interrupted treatment during the first 2 weeks, and the treatment interruption rate thereafter was constant at 1% per 14 days. CONCLUSIONS: Frequency of treatment interruption from this programme has increased recently. The strongest risk factor was year of diagnosis, perhaps reflecting the impact of an increased caseload on programme performance. Ensuring adherence to therapy in communities with a high level of migration remains a challenge even within community-based directly observed therapy programmes.

RWMODEL II: Computer simulation of the Rescorla-Wagner model of Pavlovian conditioning

RWMODEL II simulates the Rescorla-Wagner model of Pavlovian conditioning. It is written in Delphi and runs under Windows 3.1 and Windows 95. The program was designed for novice and expert users and can be employed in teaching, as well as in research. It is user friendly and requires a minimal level of computer literacy but is sufficiently flexible to permit a wide range of simulations. It allows the display of empirical data, against which predictions from the model can be validated.

Molecular characterization of the toxic cyanobacterium Cylindrospermopsis raciborskii and design of a species-specific PCR

Cylindrospermopsis raciborskii is a toxic-bloom-forming cyanobacterium that is commonly found in tropical to subtropical climatic regions worldwide, but it is also recognized as a common component of cyanobacterial communities in temperate climates. Genetic profiles of C. raciborskii were examined in 19 cultured isolates originating from geographically diverse regions of Australia and represented by two distinct morphotypes. A 609-bp region of rpoC1, a DNA-dependent RNA polymerase gene, was amplified by PCR from these isolates with cyanobacterium-specific primers. Sequence analysis revealed that all isolates belonged to the same species, including morphotypes with straight or coiled trichomes. Additional rpoC1 gene sequences obtained for a range of cyanobacteria highlighted clustering of C. raciborskii with other heterocyst-producing cyanobacteria (orders Nostocales and Stigonematales). In contrast, randomly amplified polymorphic DNA and short tandemly repeated repetitive sequence profiles revealed a greater level of genetic heterogeneity among C. raciborskii isolates than did rpoC1 gene analysis, and unique band profiles were also found among each of the cyanobacterial genera examined. A PCR test targeting a region of the rpoC1 gene unique to C. raciborskii was developed for the specific identification of C. raciborskii from both purified genomic DNA and environmental samples. The PCR was evaluated with a number of cyanobacterial isolates, but a PCR-positive result was only achieved with C, raciborskii. This method provides an accurate alternative to traditional morphological identification of C. raciborskii.

The glass ceiling hypothesis - A comparative study of the United States, Sweden, and Australia

The general-care glass ceiling hypothesis states that not only is it more difficult for women than for men to be promoted up levels of authority hierarchies within workplaces but also that the obstacles women face relative to men become greater as they move rtp the hierarchy. Gender-based discrimination in promotions is not simply present across levels of hierarchy but is more intense at higher levels. Empirically, this implies that the relative rates of women being promoted to higher levels compared to men should decline with the level of the hierarchy. This article explores this hypothesis with data from three countries: the United States, Australia, and Sweden. The basic conclusion is that while there is strong evidence for a general gender gap in authority-the odds of women having authority are less than those of men-there is no evidence for systematic glass ceiling effects in the United States and only weak evidence for such effects in the other two countries.

Public health implications of new guidelines for lead in drinking water: a case study in an area with historically high water lead levels

Concern about the neurotoxicity of lead, particularly in infants and young children, has led to a revision of blood lead levels which are considered to involve an acceptable level of human exposure. Drinking water guidelines have also been reviewed in order to reduce this source of population exposure to lead. In the last 20 years, guidelines have been reduced from 100 to 50 to 10 mu g/litre. Lead in tap water used to be a major public health problem in Glasgow because of the high prevalence of houses with lead service pipes, the low pH of the public water supply and the resulting high levels of lead in water used for public consumption. Following two separate programmes of water treatment, involving the addition of lime and, a decade later, lime supplemented with orthophosphate, it is considered that maximal measures have been taken to reduce lead exposure by chemical treatment of the water supply. Any residual problem of public exposure would require large scale replacement of lead service pipes. In anticipation of the more stringent limits for lead in drinking water, we set out to measure current lead exposure From tap water in the population of Glasgow served by the Loch Katrine water supply. to compare the current situation with 12 years previously and to assess the public health implications of different limits. The study was based on mothers of young children since maternal blood lead concentrations and the domestic water that mothers use to prepare bottle feeds are the principal sources of foetal and infant lead exposure. An estimated 17% of mothers lived in households with tap water lead concentrations of 10 mu g/litre (the WHO guideline) or above in 1993 compared with 49% in 1981. Mean maternal blood lead concentrations fell by 69% in 12 years. For a given water lead concentration, maternal blood lead concentrations were 67% lower. The mean maternal blood lead concentration was 3.7 mu g/litre in the population at large, compared with 3.3 mu g/litre in households with negligible or absent tap water lead. Nevertheless, between 63% and 76% of cases of mothers with blood lead concentrations of 10 mu g/dl or above were attributable to tap water lead. The study found that maternal blood lead concentrations were well within limits currently considered safe for human health. About 15% of infants may be exposed via bottle feeds to tap water lead concentrations that exceed the WHO guideline of 10 mu g/litre. In the context of the health and social problems which affect the well-being and development of infants and children in Glasgow, however, current levels of lend exposure are considered to present a relatively minor health problem. (C) 2000 Elsevier Science Ltd. All rights reserved.

The burden of mental disorders: a comparison of methods between the Australian burden of disease studies and the Global Burden of Disease study

The national and Victorian burden of disease studies in Australia set out to examine critically the methods used in the Global Burden of Disease study to estimate the burden of mental disorders. The main differences include the use of a different set of disability weights allowing estimates in greater detail by level of severity, adjustments for comorbidity between mental disorders, a greater number of menta I disorders measured, and model ling of substance use disorders, anxiety disorders and bipolar disorder as chronic conditions. Uniform age-weighting in the Australian studies produces considerably lower estimates of the burden due to mental disorders in comparison with age-weighted disability-adjusted life years. A lack of follow-up data on people with mental disorders who are identified in cross-sectional surveys poses the greatest challenge in determining the burden of mental disorders more accurately.

Development and standardization of the Self-regulation Skills Interview (SRSI): A new clinical assessment tool for acquired brain injury

The Self-regulation Skills Interview (SRSI) is a clinical tool designed to measure a range of metacognitive skills essential for rehabilitation planning, monitoring an individual's progress, and evaluating the outcome of treatment interventions. The results of the present study indicated that the SRSI has sound interrater reliability and test-retest reliability. A principle components analysis revealed three SRSI factors: Awareness, Readiness to Change, and Strategy Behavior. A comparison between a group of 61 participants with acquired brain injury (ABI) and a group of 43 non-brain-injured participants indicated that the participants with ABI had significantly lower levels of Awareness and Strategy Behavior, but that level of Readiness to Change was not significantly different between the two groups. The significant relationship observed between the SRSI factors and measures of neuropsychological functioning confirmed the concurrent validity of the scale and supports the value of the SRSI for post-acute assessment.

Use of advance information in patients with schizophrenia

To document possible motor disturbance in schizophrenia, we examined the ability to use advance information (or cues) to plan movements in a sequential button pressing task in 12 Clozapine medicated patients. Programming of movements under various cues revealed that patients with schizophrenia, relative to controls, initiated movements slower to the right than left, providing possible evidence for right hemineglect (left hemisphere dysfunction). Additionally, patients with schizophrenia had difficulty in the initiation of movements in the absence of a cue, suggesting internal cue generation difficulty for movement related to some form of fronto-striatal disturbance. Motor abnormalities were predominantly observed at the level of movement initiation, but not execution, contrary to basal ganglia disorders such as Parkinson's and Huntington's disease.

Influence of Mg content on the microstructure and solid solution chemistry of Al-7%Si-Mg casting alloys during solution treatment

The solution treatment stage of the T6 heat-treatment of Al-7%Si-Mg foundry alloys influences microstructural features such as Mg2Si dissolution, and eutectic silicon spheroidisation and coarsening. Microstructural and microanalytical studies have been conducted across a range of Sr-modified Al-7%Si alloys, with an Fe content of 0.12% and Mg contents ranging from 0.3-0.7wt%. Qualitative and quantitative metallography have shown that, in addition to the above changes, solution treatment also results in changes to the relative proportions of iron-containing intermetallic particles and that these changes are composition-dependent. While solution treatment causes a substantial transformation of pi phase to beta phase in low Mg alloys (0.3-0.4%), this change is not readily apparent at higher Mg levels (0.6-0.7%). The pi to beta transformation is accompanied by a release of Mg into the aluminum matrix over and above that which arises from the rapid dissolution of Mg2Si. Since the level of matrix Mg retained after quenching controls an alloy's subsequent precipitation hardening response, a proper understanding of this phase transformation is crucial if tensile properties are to be maximised.

Self-awareness and psychosocial functioning following acquired brain injury: An evaluation of a group support programme

This study investigated a group support programme designed to improve self-awareness deficits and psychosocial functioning in a group of chronic patients (N = 21) with acquired brain injury (ABI). The participants were on average 8.6 years (range: 1-36 years) post-injury and were seen at the Brain Injury Association of Queensland, Australia. The assessment of participants involved two standardised measures of intellectual self-awareness with collateral reports from relatives. The present study introduced a new measure called the Self-Regulation Skills Interview (SRSI) which assessed higher levels of self awareness and self-regulation skills. Psychosocial functioning was assessed using a standardised self-report measure. At baseline the group had a relatively high level of intellectual self-awareness regarding their deficits, a low to moderate level of self-regulation skills, and significant psychosocial impairment. The participants were involved in a 16-week group programme which involved components of cognitive rehabilitation, cognitive-behavioural therapy, and social skills training. A post-intervention assessment indicated that participants had significantly improved levels of self-regulation skills and psychosocial functioning. A 6-month follow-up assessment indicated that overall, participants had maintained the gains made during the programme. The important role of self-regulation skills is emphasised as the principle factor contributing to the maintenance of the gains observed.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Impact of increasing the re-supply interval on the seasonality of subsidised prescription use in Australia

Objective: To evaluate the impact of increasing the minimum resupply period for prescriptions on the Pharmaceutical Benefits Scheme (PBS) in November 1994. The intervention was designed to reduce the stockpiling of medicines used for chronic medical conditions under the PBS safety net. Methods: Interrupted times series regression analyses were performed on 114 months of PBS drug utilisation data from January 1991 to June 2000. These analyses assessed whether there had been a significant interaction between the onset of the intervention in November 1994 and the extreme levels of drug utilisation in the months of December (peak utilisation) and January (lowest utilisation) respectively. Both serial and 12-month lag autocorrelations were controlled for. Results: The onset of the intervention was associated with a significant reduction in the December peak in drug utilisation; after the introduction of the policy there were 1,150,196 fewer proscriptions on average or that month (95% Cl 708,333-1,592,059). There was, however, no significant change in the low level of utilisation in January. The effect of the policy appears to be decreasing across successive postintervention years. though the odds of a prescription being dispensed in December remained significantly lower in 1999 compared to each of the pre-intervention years (11% vs. 14%) Conclusion: Analysis of the impact of increasing the re-supply period for PBS prescriptions showed that the magnitude of peak utilisation in December had been markedly reduced by the policy, though this effect appears to be decreasing over time. Continued monitoring and policy review is warranted in order to ensure that the initial effect of the intervention be maintained.

The burden of mental disorders in Victoria, 1996

Background: Between 1998 and 1999, a burden of disease assessment was carried out in Victoria, Australia applying and improving on the methods of the Global Burden of Disease Study. This paper describes the methods and results of the calculations of the burden due to 22 mental disorders, adding 14 conditions not included in previous burden of disease estimates, Methods: The National Survey of Mental Health and Wellbeing provided recent data on the occurrence of the major adult mental disorders in Australia. Data from international studies and expert advice further contributed to the construction of disease models, describing each condition in terms of incidence, average duration and level of severity, with adjustments for comorbidity with other mental disorders. Disability weights for the time spent in different states of mental ill health were borrowed mainly from a study in the Netherlands, supplemented by weights derived in a local extrapolation exercise. Results: Mental disorders were the third largest group of conditions contributing to the burden of disease in Victoria, ranking behind cancers and cardiovascular diseases. Depression was the greatest cause of disability in both men and women. Eight other mental disorders in men and seven in women ranked among the top twenty causes of disability. Conclusions: Insufficient information on the natural history of many of the mental disorders, the limited information on the validity of mental disorder diagnoses in community surveys and considerable differences between ICD-10 and DSM-IV defined diagnoses were the main concerns about the accuracy of the estimates. Similar and often greater concerns have been raised in relation to the estimation of the burden from common non-fatal physical conditions such as asthma, diabetes and osteoarthritis. In comparison, psychiatric epidemiology can boast greater scientific rigour in setting standards for population surveys.