901 resultados para drug brain level
Youth alcohol and drug good practice guide 1 : a framework for youth alcohol and other drug practice
Resumo:
This Guide outlines a framework for working with young people whose AOD use creates significant vulnerability to current or future harm. The target audience is practitioners who work with young people who have problematic AOD use and the managers of these practitioners. Areas of content include the elements of a framework for AOD practice, an appreciation of the developmental, social and institutional location of young people, key concepts and understandings regarding good youth centered context responsive practice, and key policy constructs and directions.
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The main aim of this paper is to outline a proposed program of research which will attempt to quantify the extent of the problem of alcohol and other drugs in the Australian construction industry, and furthermore, develop an appropriate industry-wide policy and cultural change management program and implementation plan to address the problem. This paper will also present preliminary results from the study. The study will use qualitative and quantitative methods (in the form of interviews and surveys, respectively) to evaluate the extent of the problem of alcohol and other drug use in this industry, to ascertain the feasibility of an industry-wide policy and cultural change management program, and to develop an appropriate implementation plan. The study will be undertaken in several construction organisations, at selected sites in South Australia, Victoria and Northern Territory. It is anticipated that approximately 500 employees from the participating organisations across Australia will take part in the study. The World Health Organisation’s Alcohol Use Disorders Identification Test (AUDIT) will be used to measure the extent of alcohol use in the industry. Illicit drug use, ‘‘readiness to change’’, impediments to reducing impairment, feasibility of proposed interventions, and employee attitudes and knowledge regarding workplace AOD impairment, will also be measured through a combination of interviews and surveys. Among the preliminary findings, for 51% (n=127) of respondents, score on the AUDIT indicated alcohol use at hazardous levels. Of the respondents who were using alcohol at hazardous levels, 76% reported (n97) that they do not have a problem with drinking and 54% (n=68) reported that it would be easy to ‘‘cut down’’ or stop drinking. Nearly half (49%) of all respondents (n=122) had used marijuana/cannabis at some time prior to being surveyed. The use of other illicit substances was much less frequently reported. Preliminary interview findings indicated a lack of adequate employee knowledge regarding the physical effects of alcohol and other drugs in the workplace. As for conclusions, the proposed study will address a major gap in the literature with regard to the extent of the problem of alcohol and other drug use in the construction industry in Australia. The study will also develop and implement a national, evidence-based workplace policy, with the aim of mitigating the deleterious effects of alcohol and other drugs in this industry.
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Through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of Int-6, a component of the human translation initiation factor eIF3. Disruption of the murine Int-6 gene by mouse mammary tumor virus (MMTV) has been implicated previously in tumorigenesis, although the underlying mechanism is not yet understood. Fission yeast Int6 was shown to interact with other presumptive components of eIF3 in vivo, and was present in size fractions consistent with its incorporation into a 43S translation preinitiation complex. Drug resistance induced by Int6 overexpression was dependent on the AP-1 transcription factor Pap1, and was associated with increased abundance of Pap1-responsive mRNAs, but not with Pap1 relocalization. Fission yeast cells lacking the int6 gene grew slowly. This growth retardation could be corrected by the expression of full length Int6 of fission yeast or human origin, or by a C-terminal fragment of the fission yeast protein that also conferred drug resistance, but not by truncated human Int-6 proteins corresponding to the predicted products of MMTV-disrupted murine alleles. Studies in fission yeast may therefore help to explain the ways in which Int-6 function can be perturbed during MMTV-induced mammary tumorigenesis.
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The marsupial order Diprotodontia includes 10 extant families, which occupy all terrestrial habitats across Australia and New Guinea and have evolved remarkable dietary and locomotory diversity. Despite considerable attention, the interrelations of these families have for the most part remained elusive. In this study, we separately model mitochondrial RNA and protein-coding sequences in addition to nuclear protein-coding sequences to provide near-complete resolution of diprotodontian family-level phylogeny. We show that alternative topologies inferred in some previous studies are likely to be artifactual, resulting from branch-length and compositional biases. Subordinal groupings resolved herein include Vombatiformes (wombats and koala) and Phalangerida, which in turn comprises Petauroidea (petaurid gliders and striped, feathertail, ringtail and honey possums) and a clade whose plesiomorphic members possess blade-like premolars (phalangerid possums, kangaroos and their allies and most likely, pygmy possums). The topology resolved reveals ecological niche structuring among diprotodontians that has likely been maintained for more than 40 million years.
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We examine methodologies and methods that apply to multi-level research in the learning sciences. In so doing we describe how multiple theoretical frameworks informs the use of different methods that apply to social levels involving space-time relationships that are not accessible consciously as social life is enacted. Most of the methods involve analyses of video and audio files. Within a framework of interpretive research we present a methodology of event-oriented social science, which employs video ethnography, narrative, conversation analysis, prosody analysis, and facial expression analysis. We illustrate multi-method research in an examination of the role of emotions in teaching and learning. Conversation and prosody analyses augment facial expression analysis and ethnography. We conclude with an exploration of ways in which multi-level studies can be complemented with neural level analyses.
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The human Ureaplasma species are the most frequently isolated bacteria from the upper genital tract of pregnant women and can cause clinically asymptomatic, intra-uterine infections, which are difficult to treat with antimicrobials. Ureaplasma infection of the upper genital tract during pregnancy has been associated with numerous adverse outcomes including preterm birth, chorioamnionitis and neonatal respiratory diseases. The mechanisms by which ureaplasmas are able to chronically colonise the amniotic fluid and avoid eradication by (i) the host immune response and (ii) maternally-administered antimicrobials, remain virtually unexplored. To address this gap within the literature, this study investigated potential mechanisms by which ureaplasmas are able to cause chronic, intra-amniotic infections in an established ovine model. In this PhD program of research the effectiveness of standard, maternal erythromycin for the treatment of chronic, intra-amniotic ureaplasma infections was evaluated. At 55 days of gestation pregnant ewes received an intra-amniotic injection of either: a clinical Ureaplasma parvum serovar 3 isolate that was sensitive to macrolide antibiotics (n = 16); or 10B medium (n = 16). At 100 days of gestation, ewes were then randomised to receive either maternal erythromycin treatment (30 mg/kg/day for four days) or no treatment. Ureaplasmas were isolated from amniotic fluid, chorioamnion, umbilical cord and fetal lung specimens, which were collected at the time of preterm delivery of the fetus (125 days of gestation). Surprisingly, the numbers of ureaplasmas colonising the amniotic fluid and fetal tissues were not different between experimentally-infected animals that received erythromycin treatment or infected animals that did not receive treatment (p > 0.05), nor were there any differences in fetal inflammation and histological chorioamnionitis between these groups (p > 0.05). These data demonstrate the inability of maternal erythromycin to eradicate intra-uterine ureaplasma infections. Erythromycin was detected in the amniotic fluid of animals that received antimicrobial treatment (but not in those that did not receive treatment) by liquid chromatography-mass spectrometry; however, the concentrations were below therapeutic levels (<10 – 76 ng/mL). These findings indicate that the ineffectiveness of standard, maternal erythromycin treatment of intra-amniotic ureaplasma infections may be due to the poor placental transfer of this drug. Subsequently, the phenotypic and genotypic characteristics of ureaplasmas isolated from the amniotic fluid and chorioamnion of pregnant sheep after chronic, intra-amniotic infection and low-level exposure to erythromycin were investigated. At 55 days of gestation twelve pregnant ewes received an intra-amniotic injection of a clinical U. parvum serovar 3 isolate, which was sensitive to macrolide antibiotics. At 100 days of gestation, ewes received standard maternal erythromycin treatment (30 mg/kg/day for four days, n = 6) or saline (n = 6). Preterm fetuses were surgically delivered at 125 days of gestation and ureaplasmas were cultured from the amniotic fluid and the chorioamnion. The minimum inhibitory concentrations (MICs) of erythromycin, azithromycin and roxithromycin were determined for cultured ureaplasma isolates, and antimicrobial susceptibilities were different between ureaplasmas isolated from the amniotic fluid (MIC range = 0.08 – 1.0 mg/L) and chorioamnion (MIC range = 0.06 – 5.33 mg/L). However, the increased resistance to macrolide antibiotics observed in chorioamnion ureaplasma isolates occurred independently of exposure to erythromycin in vivo. Remarkably, domain V of the 23S ribosomal RNA gene (which is the target site of macrolide antimicrobials) of chorioamnion ureaplasmas demonstrated significant variability (125 polymorphisms out of 422 sequenced nucleotides, 29.6%) when compared to the amniotic fluid ureaplasma isolates and the inoculum strain. This sequence variability did not occur as a consequence of exposure to erythromycin, as the nucleotide substitutions were identical between chorioamnion ureaplasmas isolated from different animals, including those that did not receive erythromycin treatment. We propose that these mosaic-like 23S ribosomal RNA gene sequences may represent gene fragments transferred via horizontal gene transfer. The significant differences observed in (i) susceptibility to macrolide antimicrobials and (ii) 23S ribosomal RNA sequences of ureaplasmas isolated from the amniotic fluid and chorioamnion suggests that the anatomical site from which they were isolated may exert selective pressures that alter the socio-microbiological structure of the bacterial population, by selecting for genetic changes and altered antimicrobial susceptibility profiles. The final experiment for this PhD examined antigenic size variation of the multiple banded antigen (MBA, a surface-exposed lipoprotein and predicted ureaplasmal virulence factor) in chronic, intra-amniotic ureaplasma infections. Previously defined ‘virulent-derived’ and ‘avirulent-derived’ clonal U. parvum serovar 6 isolates (each expressing a single MBA protein) were injected into the amniotic fluid of pregnant ewes (n = 20) at 55 days of gestation, and amniotic fluid was collected by amniocentesis every two weeks until the time of near-term delivery of the fetus (at 140 days of gestation). Both the avirulent and virulent clonal ureaplasma strains generated MBA size variants (ranging in size from 32 – 170 kDa) within the amniotic fluid of pregnant ewes. The mean number of MBA size variants produced within the amniotic fluid was not different between the virulent (mean = 4.2 MBA variants) and avirulent (mean = 4.6 MBA variants) ureaplasma strains (p = 0.87). Intra-amniotic infection with the virulent strain was significantly associated with the presence of meconium-stained amniotic fluid (p = 0.01), which is an indicator of fetal distress in utero. However, the severity of histological chorioamnionitis was not different between the avirulent and virulent groups. We demonstrated that ureaplasmas were able to persist within the amniotic fluid of pregnant sheep for 85 days, despite the host mounting an innate and adaptive immune response. Pro-inflammatory cytokines (interleukin (IL)-1â, IL-6 and IL-8) were elevated within the chorioamnion tissue of pregnant sheep from both the avirulent and virulent treatment groups, and this was significantly associated with the production of anti-ureaplasma IgG antibodies within maternal sera (p < 0.05). These findings suggested that the inability of the host immune response to eradicate ureaplasmas from the amniotic cavity may be due to continual size variation of MBA surface-exposed epitopes. Taken together, these data confirm that ureaplasmas are able to cause long-term in utero infections in a sheep model, despite standard antimicrobial treatment and the development of a host immune response. The overall findings of this PhD project suggest that ureaplasmas are able to cause chronic, intra-amniotic infections due to (i) the limited placental transfer of erythromycin, which prevents the accumulation of therapeutic concentrations within the amniotic fluid; (ii) the ability of ureaplasmas to undergo rapid selection and genetic variation in vivo, resulting in ureaplasma isolates with variable MICs to macrolide antimicrobials colonising the amniotic fluid and chorioamnion; and (iii) antigenic size variation of the MBA, which may prevent eradication of ureaplasmas by the host immune response and account for differences in neonatal outcomes. The outcomes of this program of study have improved our understanding of the biology and pathogenesis of this highly adapted microorganism.
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The objective of this chapter is to provide rail practitioners with a practical approach for determining safety requirements of low-cost level crossing warning devices (LCLCWDs) on an Australian railway by way of a case study. LCLCWDs, in theory, allow railway operators to improve the safety of passively controlled crossing by upgrading a larger number of level crossings with the same budget that would otherwise be used to upgrade these using the conventional active level crossing control technologies, e.g. track circuit initiated flashing light systems. The chapter discusses the experience and obstacles of adopting LCLCWDs in Australia, and demonstrates how the risk-based approach may be used to make the case for LCLCWDs.
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This Guide is designed to assist workers better understand the and negotiate the complex interplay of ethical, legal and organisational considerations in their practice. The goal is to provide frontline workers and managers with information, questions and principles which promote good youth AOD practice. Legal information provided relates to Queensland, Australia.
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Programmed cell death (PCD) and progenitor cell generation (of glial and in some brain areas also neuronal fate) in the CNS is an active process throughout life and is generally not associated with gliosis which means that PCD can be pathologically silent. The striking discovery that progenitor cell generation (of glial and in some brain areas neuronal fate) is widespread in the adult CNS (especially the hippocampus) suggest a much more dynamic scenario than previously thought and transcends the dichotomy between neurodevelopmental and neurodegenerative models of schizophrenia and related disorders. We suggest that the regulatory processes that control the regulation of PCD and the generation of progenitor cells may be disturbed in the early phase of psychotic disorders underpinning a disconnectivity syndrom at the onset of clinically overt disorders. An ongoing 1H-MRS study of the anterior hippocampus at 3 Tesla in mostly drug-naive first-episode psychosis patients suggests no change in NAA, but significant increases in myo-inositol and lactate. The data suggests that neuronal integrity in the anterior hippocampus is still intact at the early stage of illness or mainly only functionally impaired. However the increase in lactate and myo-inositol may reflect a potential disturbance of generation and PCD of progenitor cells (of glial and in selected brain areas also neuronal fate) at the onset of psychosis. If true the use of neuroprotective agents such as lithium or eicosapentaenoic acid (which inhibit PCD and support cell generation)in the early phase of psychotic disorders may be a potent treatment avenue to explore.
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Decline of alertness constitutes a normal physiological phenomenon but could be aggravated when drivers operate in monotonous environments, even in rested individuals. Driving performance is impaired and this increases crash risk due to inattention. This paper aims to show that road characteristics - namely road design (road geometry) and road side variability (signage and buildings) – influence subjective assessment of alertness by drivers. This study used a driving simulator to investigate the drivers’ ability to subjectively detect periods of time when their alertness is importantly reduced by varying road geometry and road environment. Driver’s EEG activity is recorded as a reference to evaluate objectively driver's alertness and is compared to self-reported alertness by participants. Twenty-five participants drove on four different scenarios (varying road design and road environment monotony) for forty minutes. It was observed that participants were significantly more accurate in their assessment before the driving task as compared to after (90% versus 60%). Errors in assessment were largely underestimations of their real alertness rather than over-estimations. The ability to detect low alertness as assessed with an EEG was highly dependent on the road monotony. Scenarios with low roadside variability resulted in high overestimation of the real alertness, which was not observed on monotonous road design. The findings have consequences for road safety and suggest that countermeasures to lapses of alertness cannot rely solely on self-assessment from drivers and road design should reduce environments with low variability.