Evidence for a QTL on chromosome 19 influencing LDL cholesterol levels in the general population

The genetic basis of cardiovascular disease (CVD) with its complex etiology is still largely elusive. Plasma levels of lipids and apolipoproteins are among the major quantitative risk factors for CVD and are well-established intermediate traits that may be more accessible to genetic dissection than clinical CVD end points. Chromosome 19 harbors multiple genes that have been suggested to play a role in lipid metabolism and previous studies indicated the presence of a quantitative trait locus (QTL) for cholesterol levels in genetic isolates. To establish the relevance of genetic variation at chromosome 19 for plasma levels of lipids and apolipoproteins in the general, out-bred Caucasian population, we performed a linkage study in four independent samples, including adolescent Dutch twins and adult Dutch, Swedish and Australian twins totaling 493 dizygotic twin pairs. The average spacing of short-tandem-repeat markers was 6 - 8 cM. In the three adult twin samples, we found consistent evidence for linkage of chromosome 19 with LDL cholesterol levels ( maximum LOD scores of 4.5, 1.7 and 2.1 in the Dutch, Swedish and Australian sample, respectively); no indication for linkage was observed in the adolescent Dutch twin sample. The QTL effects in the three adult samples were not significantly different and a simultaneous analysis of the samples increased the maximum LOD score to 5.7 at 60 cM pter. Bivariate analyses indicated that the putative LDL-C QTL also contributed to the variance in ApoB levels, consistent with the high genetic correlation between these phenotypes. Our study provides strong evidence for the presence of a QTL on chromosome 19 with a major effect on LDL-C plasma levels in outbred Caucasian populations.

Using a non-invasive stable isotope tracer to measure the absorption of water in humans

The development of solutions that prevent dehydration or promote adequate re-hydration play a vital role in preventing fatigue during exercise, however, the methods commonly used to assess the hydration ability of such solutions are invasive and often assess the components of absorption separately. This paper describes using a non-invasive deuterium tracer technique that assesses gastric emptying and intestinal absorption simultaneously to evaluate the uptake of water during rest and exercise. The kinetics of absorption are further examined by mathematical modelling of the data generated. For the rest group, 0.05 g/kg of body weight of deuterium, contained in gelatine capsules, was ingested with ordinary tap water and saliva samples were collected every 5 min for one hour while the subject remained seated. The deuterium was administered as above for the exercise group but sample collection was during one hour of exercise on a treadmill at 55% of the subject's maximum heart rate. The enrichment data for each subject were mathematically modelled and the parameters obtained were compared across groups using an independent samples t-test. Compared with the rest condition, the exercise group showed delayed absorption of water as indicated by significant differences for the modelling parameters t(2), t(1/2), maximum absorption rate and solution absorption amount at t(1). Labelling with a deuterium tracer is a good measure of the relative rate ingested fluids are absorbed by the body. Mathematical modelling of the data generates rates of maximum absorption and allows calculation of the percentage of the solution that is absorbed at any given time during the testing period. Copyright (C) 2004 John Wiley Sons, Ltd.

The effect of pre-clinical fieldwork subject on the confidence and professional skills of undergraduate occupational therapy students

Objectives: This study investigated the effect of a pre-clinical fieldwork subject on the confidence and professional skills of undergraduate occupational therapy students during their first full-time clinical fieldwork placement. Methods: Participants were 31 third year students enrolled in the pre-clinical fieldwork subject (experimental group), and 25 students not enrolled in the subject (control group). Both quantitative and qualitative methodologies were employed to address the research question. Student anxiety levels were measured using the State-Trait Anxiety Inventory (STAI) and compared at three different intervals - prior to commencing the university semester, prior to commencing full-time practical placement, and following this full-time placement. Individual interviews were conducted with six students (three from the experimental group, three from the control group) to explore their perceptions regarding confidence levels and skill proficiencies during full-time placement. At each data analysis interval, responses for both groups were compared using independent samples t-tests. Responses were compared over time using analysis of variance (ANOVA). The qualitative data were subjected to thematic and content analysis. Results and Conclusions: In general, student anxiety levels did not differ between the experimental and control groups over time. However, qualitative results suggest that students who were enrolled in the pre-clinical subject have greater confidence and competence with occupational therapy skills, and have heightened awareness of the expectations on full-time placement.

Experimental evidence for multivariate stabilizing sexual selection

Stabilizing selection is a fundamental concept in evolutionary biology. In the presence of a single intermediate optimum phenotype (fitness peak) on the fitness surface, stabilizing selection should cause the population to evolve toward such a peak. This prediction has seldom been tested, particularly for suites of correlated traits. The lack of tests for an evolutionary match between population means and adaptive peaks may be due, at least in part, to problems associated with empirically detecting multivariate stabilizing selection and with testing whether population means are at the peak of multivariate fitness surfaces. Here we show how canonical analysis of the fitness surface, combined with the estimation of confidence regions for stationary points on quadratic response surfaces, may be used to define multivariate stabilizing selection on a suite of traits and to establish whether natural populations reside on the multivariate peak. We manufactured artificial advertisement calls of the male cricket Teleogryllus commodus and played them back to females in laboratory phonotaxis trials to estimate the linear and nonlinear sexual selection that female phonotactic choice imposes on male call structure. Significant nonlinear selection on the major axes of the fitness surface was convex in nature and displayed an intermediate optimum, indicating multivariate stabilizing selection. The mean phenotypes of four independent samples of males, from the same population as the females used in phonotaxis trials, were within the 95% confidence region for the fitness peak. These experiments indicate that stabilizing sexual selection may play an important role in the evolution of male call properties in natural populations of T. commodus.

Development and evaluation of a youth mental health community awareness campaign - The Compass Strategy

Background: Early detection and treatment of mental disorders in adolescents and young adults can lead to better health outcomes. Mental health literacy is a key to early recognition and help seeking. Whilst a number of population health initiatives have attempted to improve mental health literacy, none to date have specifically targeted young people nor have they applied the rigorous standards of population health models now accepted as best practice in other health areas. This paper describes the outcomes from the application of a health promotion model to the development, implementation and evaluation of a community awareness campaign designed to improve mental health literacy and early help seeking amongst young people. Method: The Compass Strategy was implemented in the western metropolitan Melbourne and Barwon regions of Victoria, Australia. The Precede-Proceed Model guided the population assessment, campaign strategy development and evaluation. The campaign included the use of multimedia, a website, and an information telephone service. Multiple levels of evaluation were conducted. This included a cross-sectional telephone survey of mental health literacy undertaken before and after 14 months of the campaign using a quasi-experimental design. Randomly selected independent samples of 600 young people aged 12 - 25 years from the experimental region and another 600 from a comparison region were interviewed at each time point. A series of binary logistic regression analyses were used to measure the association between a range of campaign outcome variables and the predictor variables of region and time. Results: The program was judged to have an impact on the following variables, as indicated by significant region-by-time interaction effects ( p < 0.05): awareness of mental health campaigns, self-identified depression, help for depression sought in the previous year, correct estimate of prevalence of mental health problems, increased awareness of suicide risk, and a reduction in perceived barriers to help seeking. These effects may be underestimated because media distribution error resulted in a small amount of print material leaking into the comparison region. Conclusion: We believe this is the first study to apply the rigorous standards of a health promotion model including the use of a control region to a mental health population intervention. The program achieved many of its aims despite the relatively short duration and moderate intensity of the campaign.

Quantifying aphasic people's social lives in the context of non-aphasic peers

Background: Developing the knowledge base on the impact of aphasia on people's social lives has become increasingly important in recent times to further our understanding of the broad consequences of communication disability and thus provide appropriate services. Past research clearly indicates that relationships and social activities with family members and others undergo change with the onset of aphasia in an individual, however more evidence of a quantitative nature would be beneficial. Aims: The current research furthers our knowledge by quantifying chronically aphasic older people's regular social contacts and social activities, and places them in context by comparing them with healthy older people of similar age and education. Methods & Procedures: A total of 30 aphasic participants aged 57 to 88 years, and 71 non-aphasic controls aged 62 to 98 years were interviewed by a speech and language therapist using self-report measures of Social Network Analysis (Antonucci & Akiyama, 1987) and Social Activities Checklist (Cruice, 2001, in Worrall & Hickson, 2003). Demographic information was also collected. Descriptive statistics are presented and independent samples t tests were used to examine differences between the groups. Outcomes & Results: Participants with primarily mild to moderate aphasic impairment reported a considerable range of social contacts (5-51) and social activities (8-18). Many significant differences were evident between the two groups' social contacts and activities. On average, aphasic participants had nine fewer social contacts (mainly friend'' relationships) and three fewer social activities (mainly leisure'' activities) than their non-aphasic peers. The majority of controls were satisfied with their social activities, whereas the majority of aphasic participants were not and wanted to be doing more. There were some general similarities between the groups, in terms of range of social contacts, overall pattern of social relationships, and core social activities. Conclusions: Older people with chronic aphasia had significantly fewer social contacts and social activities than their peers. People with aphasia expressed a desire to increase the social activity of their lives. Given the importance of leisure activity and relationships with friends as well as family for positive well-being, speech and language therapists may direct their rehabilitation efforts towards two areas: (1) conversational partner programmes training friends to maintain these relationships; and (2) encouraging and supporting aphasic clients in leisure activities of their choice.

Bacterial community structure associated with white band disease in the elkhorn coral Acropora palmata determined using culture-independent 16S rRNA techniques

Culture-independent molecular (16S ribosomal RNA) techniques showed distinct differences in bacterial communities associated with white band disease (WBD) Type I and healthy elkhorn coral Acropora palmata. Differences were apparent at all levels, with a greater diversity present in tissues of diseased colonies. The bacterial community associated with remote, non-diseased coral was distinct from the apparently healthy tissues of infected corals several cm from the disease lesion. This demonstrates a whole-organism effect from what appears to be a localised disease lesion, an effect that has also been recently demonstrated in white plague-like disease in star coral Montastraea annularis. The pattern of bacterial community structure changes was similar to that recently demonstrated for white plague-like disease and black band disease. Some of the changes are likely to be explained by the colonisation of dead and degrading tissues by a micro-heterotroph community adapted to the decomposition of coral tissues. However, specific ribosomal types that are absent from healthy tissues appear consistently in all samples of each of the diseases. These ribotypes are closely related members of a group of alpha-proteobacteria that cause disease, notably juvenile oyster disease, in other marine organisms. It is clearly important that members of this group are isolated for challenge experiments to determine their role in the diseases.

Fluctuations in heroin purity and the incidence of fatal heroin overdose

In order to determine the role played by heroin purity in fatal heroin overdoses, time series analyses were conducted on the purity of street heroin seizures in south western Sydney and overdose fatalities in that region. A total of 322 heroin samples were analysed in fortnightly periods between February 1993 to January 1995. A total of 61 overdose deaths occurred in the region in the study period. Cross correlation plots revealed a significant correlation of 0.57 at time lag zero between mean purity of heroin samples per fortnight and number of overdose fatalities. Similarly, there was a significant correlation of 0.50 at time lag zero between the highest heroin purity per fortnight and number of overdose fatalities. The correlation between range of heroin purity and number of deaths per fortnight was 0.40. A simultaneous multiple regression on scores adjusted for first order correlation indicated both the mean level of heroin purity and the range of heroin purity were independent predictors of the number of deaths per fortnight. The results indicate that the occurrence of overdose fatalities was moderately associated with both the average heroin purity and the range of heroin purity over the study period. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

The N-15 natural abundance (delta N-15) of ecosystem samples reflects measures of water availability

We assembled a globally-derived data set for site-averaged foliar delta(15)N, the delta(15)N of whole surface mineral soil and corresponding site factors (mean annual rainfall and temperature, latitude, altitude and soil pH). The delta(15)N of whole soil was related to all of the site variables (including foliar delta(15)N) except altitude and, when regressed on latitude and rainfall, provided the best model of these data, accounting for 49% of the variation in whole soil delta(15)N. As single linear regressions, site-averaged foliar delta(15)N was more strongly related to rainfall than was whole soil delta(15)N. A smaller data set showed similar, negative correlations between whole soil delta(15)N, site-averaged foliar delta(15)N and soil moisture variations during a single growing season. The negative correlation between water availability (measured here by rainfall and temperature) and soil or plant delta(15)N fails at the landscape scale, where wet spots are delta(15)N-enriched relative to their drier surroundings. Here we present global and seasonal data, postulate a proximate mechanism for the overall relationship between water availability and ecosystem delta(15)N and, newly, a mechanism accounting for the highly delta(15)N-depleted values found in the foliage and soils of many wet/cold ecosystems. These hypotheses are complemented by documentation of the present gaps in knowledge, suggesting lines of research which will provide new insights into terrestrial N-cycling. Our conclusions are consistent with those of Austin and Vitousek (1998) that foliar (and soil) delta(15)N appear to be related to the residence time of whole ecosystem N.

Percolative fragmentation of char particles during gasification

Percolative fragmentation was confirmed to occur during gasification of three microporous coal chars. Indirect evidence obtained by the variation of electrical resistivity (ER) with conversion was supported by direct observation of numerous fragments during gasification. The resistivity increases slowly at low conversions and then sharply after a certain conversion value, which is a typical percolation phenomenon suggesting the occurrence of internal fragmentation at high conversion. Two percolation models are applied to interpret the experimental data and determine the percolation threshold. A percolation threshold of 0.02-0.07 was found, corresponding to a critical conversion of 92-96% for fragmentation. The electrical resistivity variation at high conversions is found to be very sensitive to diffusional effects during gasification. Partially burnt samples with a narrow initial particle size range were also observed microscopically, and found to yield a large number of small fragments even when the particles showed no disintegration and chemical control prevailed. It is proposed that this is due to the separation of isolated clusters from the particle surface. The particle size distribution of the fragments was essentially independent of the reaction conditions and the char type, and supported the prediction by percolation theory that the number fraction distribution varies linearly with mass in a log-log plot. The results imply that perimeter fragmentation would occur in practical combustion systems in which the reactions are strongly diffusion affected.

Redating the onset of burning at Lynch's Crater (North Queensland): implications for human settlement in Australia

Lynch's Crater preserves a continuous, high-resolution record of environmental changes in north Queensland. This record suggests a marked increase in burning that appears to be independent of any known major climatic boundaries. This increase is accompanied, or closely followed, by the virtually complete replacement of rainforest by sclerophyll vegetation. The absence of any major climatic shift associated with this increase in fire frequency therefore has been interpreted as a result of early human impact in the area. The age for this increase in burning, on the basis of conventional radiocarbon dating, was previously thought to be approximately 38000 C-14 yr BP, supporting the traditional model for human arrival in Australia at 40 000 C-14 yr BP Here we have applied a more rigorous pre-treatment and graphitisation procedure for radiocarbon dating samples from the Lynch's Crater sequence. These new dates suggest that the increase in fire frequency occurred at 45 000 C-14 yr BP, supporting the alternative view that human occupation of Australia occurred by at least 45 000-55 000 cal. yr BP. Copyright (C) 2001 John Wiley & Sons, Ltd.

Large mitochondrial repeats multiplied during the polymerase chain reaction

The number of repeats in repetitive DNA like micro- and minisatellites is often determined by polymerase chain reaction (PCR). When we counted repeats in an array of mitochondrial repeats in the cattle tick (Boophilus microplus) we found that the number of repeats increased during PCR. Multiplication of the repeats was independent of the primers used to amplify the region, the PCR annealing temperature and the length of the PCR product. The use of PCR to determine the number of repeats in arrays needs to be reassessed. For long repeats, a subset of samples should always be analysed by Southern blot hybridization to confirm the PCR results.

Myb-binding Protein 1a is a Nucleocytoplasmic Shuttling Protein that Utilizes CRM1-dependent and Independent Nuclear Export Pathways

Myb-binding protein 1a (Mybbp1a) is a novel nuclear protein localized predominantly, but not exclusively, in nucleoli. Although initially isolated as a c-Myb interacting protein, Mybbp1a is expressed ubiquitously, associates with a number of different transcription factors, and may play a role in both RNA polymerase I- and II-mediated transcriptional regulation. However, its precise function remains unclear. In this study we show that Mybbp1a is a nucleocytoplasmic shuttling protein and investigate the mechanisms responsible for both nuclear import and export. The carboxyl terminus of Mybbp1a, which contains seven short basic amino acid repeat sequences, is responsible for both nuclear and nucleolar localization, and this activity can be transferred to a heterologous protein. Deletion mapping demonstrated that these repeat sequences appear to act incrementally, with successive deletions resulting in a corresponding increase in the proportion of protein localized in the cytoplasm. Glutathione S-transferase pulldown experiments showed that the nuclear receptor importin-alpha/beta mediates Mybbp1a nuclear import. Interspecies heterokaryons were used to demonstrate that Mybbp1a was capable of shuttling between the nucleus and the cytoplasm. Deletion analysis and in vivo export studies using a heterologous assay system identified several nuclear export sequences which facilitate Mybbp1a nuclear export of Mybbp1a by CRM1-dependent and -independent pathways. (C) 2003 Elsevier Science (USA). All rights reserved.