GAD2 on chromosome 10p12 is a candidate gene for human obesity

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11&ndash;12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of &gamma;-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C>A and +83897 T>A (OR = 0.81, 95% CI [0.681&ndash;0.972], p = 0.0049) and an at-risk SNP (−243 A>G) for morbid obesity (OR = 1.3, 95% CI [1.053&ndash;1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C>A and +83897 T>A haplotype (χ2 = 7.637, p = 0.02). In the murine insulinoma cell line &beta;TC3, the G at-risk allele of SNP −243 A>G increased six times GAD2 promoter activity (p < 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The −243 A>G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic &beta; cells, we analyzed GAD65 antibody level as a marker of &beta;-cell activity and of insulin secretion. In the control group, −243 A>G, +61450 C>A, and +83897 T>A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T>A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of &beta;-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.<br />

The current pattern of hepatitis B virus infectiion in Australia

Summary. There is little recent data of the seroprevalence of hepatitis B in Australia. We have surveyed a large cohort of endoscopy patients attending a teaching hospital in central Sydney, and related the presence of hepatitis B virus (HBV) markers with putative risk factors for exposure using the SAS statistical package. Of the 2115 patients tested: 2.1% (45/2115) were HBV surface antigen positive, 0.75% (14/2115) viraemic, 9.5% (200/2115) anti-HBs and anti-HBc positive, 20.1% (430/2115) vaccinated (anti-HBs only) and the remaining 70% were susceptible. The adjusted OR of HBV infection was significantly increased in patients who had been diagnosed with human immunodeficiency virus (36.3-fold), born in Asia or Pacific islands (12.4-fold), born in North Africa, Middle East &amp; Mediterranean countries (6-fold) or born abroad elsewhere in the world (2.7-fold), had household contact with someone diagnosed with hepatitis between 1980 and 1990 (3.9-fold), injected drugs between 1980 and 1990 (4.4-fold), resided in a military establishment for 3 months (2.3-fold) or in a hospital for 3 months (2.2-fold), never been vaccinated for hepatitis B (2.8-fold), received blood transfusion due to an accident and/or a haemorrhage (1.92-fold) and finally been a male gender (1.59-fold). The prevalence of HBV in this hospital population was higher than predicted on the basis of notifications to the passive surveillance scheme. Most HBV patients had multiple risk factors for infection, but the hierarchy of odds ratios provides a rational basis for targeted programmes to identify asymptomatic HBV carriers who might benefit from treatment.

A new rodent model to assess blood stage immunity to the plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119&ndash;specific inhibitory antibodies, but not with titres of total MSP-119&ndash;specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines. <br />

What have sampling and data collection got to do with good qualitative research?

<b>Objective:b> To highlight the importance of sampling and data collection&nbsp; processes in qualitative interview studies, and to discuss the contribution of&nbsp; these processes to determining the strength of the evidence generated and&nbsp; thereby to decisions for public health practice and policy. <br /><b><br />Approach:b> This discussion is informed by a hierarchy-of-evidence-for-practice&nbsp; model. The paper provides succinct guidelines for key sampling and data&nbsp; collection considerations in qualitative research involving interview studies. The&nbsp; importance of allowing time for immersion in a given community to become&nbsp; familiar with the context and population is discussed, as well as the practical&nbsp; constraints that sometimes operate against this stage. The role of theory in&nbsp; guiding sample selection is discussed both in terms of identifying likely sources&nbsp; of rich data and in understanding the issues emerging from the data. It is noted&nbsp; that sampling further assists in confirming the developing evidence and also&nbsp; illuminates data that does not seem to fit. The importance of reporting sampling&nbsp; and data collection processes is highlighted clearly to enable others to assess&nbsp; both the strength of the evidence and the broader applications of the findings.<br /><b><br />Conclusion: b>Sampling and data collection processes are critical to determining&nbsp; the quality of a study and the generalisability of the findings. We argue that&nbsp; these processes should operate within the parameters of the research goal, be&nbsp; guided by emerging theoretical considerations, cover a range of relevant&nbsp;&nbsp; participant perspectives, and be clearly outlined in research reports with an&nbsp; explanation of any research limitations.<br />

Regional-scale models for relating land cover to basin surface-water quality using remotely sensed data in a GIS

Plant-based management systems implementing deep-rooted, perennial vegetation have been identified as important in mitigating the spread of secondary dryland salinity due to its capacity to influence water table depth. The Glenelg Hopkins catchment is a highly modified watershed in the southwest region of Victoria, where dryland salinity management has been identified as a priority. Empirical relationships between the proportion of native vegetation and in-stream salinity were examined in the Glenelg Hopkins catchment using a linear regression approach. Whilst investigations of these relationships are not unique, this is the first comprehensive attempt to establish a link between land use and in-stream salinity in the study area. The results indicate that higher percentage land cover with native vegetation was negatively correlated with elevated in-stream salinity. This inverse correlation was consistent across the 3 years examined (1980, 1995, and 2002). Recognising the potential for erroneously inferring causal relationships, the methodology outlined here was both a time and cost-effective tool to inform management strategies at a regional scale, particularly in areas where processes may be operating at scales not easily addressed with on-site studies.<br />

Finding edging genes from microarray data

<b>Motivationb>: A set of genes and their gene expression levels are used to classify disease and normal tissues. Due to the massive number of genes in microarray, there are a large number of edges to divide different classes of genes in microarray space. The edging genes (EGs) can be co-regulated genes, they can also be on the same pathway or deregulated by the same non-coding genes, such as siRNA or miRNA. Every gene in EGs is vital for identifying a tissue's class. The changing in one EG's gene expression may cause a tissue alteration from normal to disease and vice versa. Finding EGs is of biological importance. In this work, we propose an algorithm to effectively find these EGs.<br /><b><br />Resultb>: We tested our algorithm with five microarray datasets. The results are compared with the border-based algorithm which was used to find gene groups and subsequently divide different classes of tissues. Our algorithm finds a significantly larger amount of EGs than does the border-based algorithm. As our algorithm prunes irrelevant patterns at earlier stages, time and space complexities are much less prevalent than in the border-based algorithm.<br />

Intake of B vitamins in childhood and adult life in relation to psychological distress among women in a British birth cohort

<b>Background : b>Lower levels of B vitamins (particularly folate, vitamin B12 and vitamin B6) may be associated with psychological distress. Little is known about the impact of childhood nutrition on psychological distress in adult life.<br /><br /><b>Objective :b> We investigated whether prospectively measured childhood and adult dietary intakes of thiamin, riboflavin, niacin, folate, vitamin B6 and vitamin B12 were related to the psychological distress of women in mid-age, taking into account socio-economic, behavioural and lifestyle factors.<br /><b><br />Design :b> Prospective data were collected from a cohort of 636 British women followed up since their birth in 1946. Participants completed a 28-item, scaled version of the General Health Questionnaire (GHQ-28) to measure psychological distress at age 53 years. Dietary intakes in childhood (at age four) were determined by 24h recall and in adulthood (at age 36, 43 and 53 years) by a 5d food record.<br /><br /><b>Results :b> Low dietary vitamin B12 intake at age 53 was associated with higher psychological distress at that age. Women in the lowest third of vitamin B12 intake in adulthood had a higher GHQ-28 score compared with those in the highest third (percentage change, adjusted regression coefficient, 21 (95% CI 3, 39)). There were no other significant associations between dietary B vitamin intake in childhood or adulthood and psychological distress in the cohort.<br /><br /><b>Conclusions :b> Overall, there is evidence that intake of vitamin B12 at age 53 is related to adult psychological distress but there is no evidence for the effects of other adult B vitamin intakes or childhood intakes on psychological distress.<br />

Effectiveness of vertebroplasty using individual patient data from two randomised placebo controlled trials : meta-analysis

<b>Objectiveb> To determine whether vertebroplasty is more effective than placebo for patients with pain of recent onset (≤6 weeks) or severe pain (score ≥8 on 0-10 numerical rating scale).<br /><br /><b>Designb> Meta-analysis of combined individual patient level data.<br /><br /><b>Settingb> Two multicentred randomised controlled trials of vertebroplasty; one based in Australia, the other in the United States.<br /><br /><b>Participants b>209 participants (Australian trial n=78, US trial n=131) with at least one radiographically confirmed vertebral compression fracture. 57 (27%) participants had pain of recent onset (vertebroplasty n=25, placebo n=32) and 99 (47%) had severe pain at baseline (vertebroplasty n=50, placebo n=49).<br /><br /><b>Intervention b>Percutaneous vertebroplasty versus a placebo procedure.<br /><br /><b>Main outcome measureb> Scores for pain (0-10 scale) and function (modified, 23 item Roland-Morris disability questionnaire) at one month.<br /><br /><b>Results b>For participants with pain of recent onset, between group differences in mean change scores at one month for pain and disability were 0.1 (95% confidence interval −1.4 to 1.6) and 0.2 (−3.0 to 3.4), respectively. For participants with severe pain at baseline, between group differences for pain and disability scores at one month were 0.3 (−0.8 to 1.5) and 1.4 (−1.2 to 3.9), respectively. At one month those in the vertebroplasty group were more likely to be using opioids.<br /><br /><b>Conclusions b>Individual patient data meta-analysis from two blinded trials of vertebroplasty, powered for subgroup analyses, failed to show an advantage of vertebroplasty over placebo for participants with recent onset fracture or severe pain. These results do not support the hypothesis that selected subgroups would benefit from vertebroplasty.<br />

Prevalence of obesity and the relationship between the body mass index and body fat : cross-sectional, population-based data

<b>Backgroundb>: Anthropometric measures such as the body mass index (BMI) and waist circumference are widely used as convenient indices of adiposity, yet there are limitations in their estimates of body fat. We aimed to determine the prevalence of obesity using criteria based on the BMI and waist circumference, and to examine the relationship between the BMI and body fat.<br /><br /><b>Methodology/Principal Findingsb>: This population-based, cross-sectional study was conducted as part of the Geelong Osteoporosis Study. A random sample of 1,467 men and 1,076 women aged 20&ndash;96 years was assessed 2001&ndash;2008. Overweight and obesity were identified according to BMI (overweight 25.0&ndash;29.9 kg/m2; obesity $30.0 kg/m2) and waist circumference (overweight men 94.0&ndash;101.9 cm; women 80.0&ndash;87.9 cm; obesity men $102.0 cm, women $88.0 cm); body fat mass was assessed using dual energy X-ray absorptiometry; height and weight were measured and lifestyle factors documented by self-report. According to the BMI, 45.1% (95%CI 42.4&ndash;47.9) of men and 30.2% (95%CI 27.4&ndash;33.0) of women were overweight and a further 20.2% (95%CI 18.0&ndash;22.4) of men and 28.6% (95%CI 25.8&ndash;31.3) of women were obese. Using waist circumference, 27.5% (95%CI 25.1&ndash;30.0) of men and 23.3% (95%CI 20.8&ndash;25.9) of women were overweight, and 29.3% (95%CI 26.9&ndash;31.7) of men and 44.1% (95%CI 41.2&ndash;47.1) of women, obese. Both criteria indicate that approximately 60% of the population exceeded recommended thresholds for healthy body habitus. There was no consistent pattern apparent between BMI and energy intake. Compared with women, BMI overestimated adiposity in men, whose excess weight was largely attributable to muscular body builds and greater bone mass. BMI also underestimated adiposity in the elderly. Regression models including gender, age and BMI explained 0.825 of the variance in percent body fat.<br /><br /><b>Conclusions/Significanceb>: As the BMI does not account for differences in body composition, we suggest that gender- and age-specific thresholds should be considered when the BMI is used to indicate adiposity.<br />

Patterns and correlates of self-reported racial discrimination among Australian Aboriginal and Torres Strait Islander adults, 2008–09: analysis of national survey data

<b>Backgroundb><br />There is now considerable evidence that racism is a pernicious and enduring social problem with a wide range of detrimental outcomes for individuals, communities and societies. Although indigenous people worldwide are subjected to high levels of racism, there is a paucity of population-based, quantitative data about the factors associated with their reporting of racial discrimination, about the settings in which such discrimination takes place, and about the frequency with which it is experienced. Such information is essential in efforts to reduce both exposure to racism among indigenous people and the harms associated with such exposure.<br /><br /><b>Methodsb><br />Weighted data on self-reported racial discrimination from over 7,000 Indigenous Australian adults participating in the 2008&ndash;09 National Aboriginal and Torres Strait Islander Survey, a nationally representative survey conducted by the Australian Bureau of Statistics, were analysed by socioeconomic, demographic and cultural factors.<br /><br /><b>Resultsb><br />More than one in four respondents (27%) reported experiencing racial discrimination in the past year. Racial discrimination was most commonly reported in public (41% of those reporting any racial discrimination), legal (40%) and work (30%) settings. Among those reporting any racial discrimination, about 40% experienced this discrimination most or all of the time (as opposed to a little or some of the time) in at least one setting. Reporting of racial discrimination peaked in the 35&ndash;44 year age group and then declined. Higher reporting of racial discrimination was associated with removal from family, low trust, unemployment, having a university degree, and indicators of cultural identity and participation. Lower reporting of racial discrimination was associated with home ownership, remote residence and having relatively few Indigenous friends.<br /><br /><b>Conclusionsb><br />These data indicate that racial discrimination is commonly experienced across a wide variety of settings, with public, legal and work settings identified as particularly salient. The observed relationships, while not necessarily causal, help to build a detailed picture of self-reported racial discrimination experienced by Indigenous people in contemporary Australia, providing important evidence to inform anti-racism policy.

In-vivo cell mediated immunity in elite swimmers in response to training

This study investigated in-vivo cell-mediated immune (CMI) responses in elite swimmers over a 5-month training season, to assess the impact of intense training on changes in T-lymphocyte function. The CMI Multitest was performed early in the season after a period of rest, during peak high-intensity training, and late in the season during the precompetition taper period. The CMI tests were performed at rest prior to a morning training session. There were no significant differences between the swimmers and a control group for any of the seven CMI antigen responses at any of the test points during the season. In the swimmers, there were no significant differences in the number of positive responses to the CMI antigens between the three test points (Friedman's test = 9.6364, p = 0.47) and no significant differences for the CMI cumulative scores (Friedman's test = 11.98, p = 0.29) at each test point. There was no consistent pattern for changes in CMI cumulative scores for individual swimmers over the training season. The findings of this study indicate that, despite reported transient T-lymphocyte immunosuppression immediately after intense exercise, probably associated with acute redistribution and temporary pooling of blood T cell subsets in extremities, the T-lymphocyte function involved in CMI responses is not compromised by extended periods of training at an elite level.

Communicating the ethos of codes of ethics in corporate Australia, 1995-2001: whose rights, whose responsibilities?

This paper considers the commitment to business ethics of the top 500 companies operating in the Australian private sector and communicates the results of a longitudinal study conducted from 1995 to 2001. Primary data was obtained (in 1995 and again in 2001) via a self-administered mail&nbsp; questionnaire distributed to a census of these top 500 Australian&nbsp; companies. This commitment of each company to their code of ethics was indicated and measured via a range of methods used by organizations to communicate the ethos of their codes to employees. Just as they were in&nbsp; 1995, it would appear that companies in 2001 still are good at ensuring that their rights are protected, but at the same time they do not seem to take on the responsibility to ensure that employees'' rights are just as well protected. This double standard leads to cynicism towards the current business ethics processes inherent in Australian companies.<br />

Effects of timed voiding for the management of uninary incontinence in adults: systematic review

<b>Aimb>: The aim of this paper is to present a systematic review assessing the effectiveness of timed voiding for the management of urinary incontinence in adults. Background: Despite the widespread use of systematic voiding programmes, their effectiveness is unclear, and the evidence for timed voiding has not been subject to rigorous and systematic evaluation. The impact on psychosocial factors and cost is also untested. The physiological basis for timed voiding is also poorly established. <b>Methodsb>: The systematic review incorporated the methodology of the Cochrane Collaboration. All randomized or quasi-randomized controlled trials that addressed timed voiding for the management of urinary incontinence in adults were searched, appraised, analysed and summarized. The date of the latest search was 2002. Data were extracted independently and appraised according to the level of concealment of random allocation prior to formal entry; few and identifiable withdrawals and dropouts and an analysis based on an intention to treat. The relative risk for dichotomous data was calculated with 95% confidence intervals. Where data were insufficient to support quantitative analysis, a narrative overview was undertaken. <b>Resultsb>: Two trials of timed voiding met the inclusion criteria. In both, timed voiding was combined with other strategies. Participants were predominantly cognitively and physically impaired older women who resided in nursing home settings. Within-group improvements for the intervention groups were reported for both trials. One trial additionally reported a statistically significant reduction in night-time incontinence for the intervention group. The quality of the trials was modest and interpretation was limited by the potential for bias associated with inadequate concealment, missing data and no analysis by intention to treat. <b>Conclusionb>: Terms used to describe voiding programmes that involve a fixed interval of voiding are variable. No conclusions can be drawn at this point about the effectiveness of timed voiding for the management of urinary incontinence in adults.<br />

Development, implementation, and evaluation of a continence education package in acute and subacute care settings

<b>OBJECTIVE: b>The objective of the study was to trial and evaluate the effect that a discharge Continence Education Package (CEP) had on patients' continence awareness and management preferences.<br /><b>DESIGN:b> An exploratory descriptive design was used.<br /><b>SETTINGS AND SUBJECTS: b>A total of 631 participants were included in the study: 352 females (55.8%) and 279 males (44.2%) from 4 rural and regional settings in Victoria, Australia.<br /><b>INSTRUMENTS AND METHODS:b> A specifically designed questionnaire was used to assess participants' knowledge of incontinence and its management and also to investigate their treatment preferences and intentions if they experienced this type of problem. Data were collected at 2 time periods. Specifically, patients were interviewed before discharge from acute and subacute settings identified as Time 1 (T1). Then the participants were given the CEP and asked to complete a similar questionnaire.<br /><b>RESULTS: b>The findings revealed that fewer than 25% of participants had received information on continence before the study being conducted, yet the majority had indicated that they had experienced continence symptoms. The majority of participants found the CEP easy to understand (98.2%) and helpful (95.3%). Most participants said it provided them with information about types of actions to take and/or treatment options for incontinence problems. It also raised their awareness of the signs and symptoms associated with incontinence and provided them with a useful self-administered gauge with which to assess their continence status.<br /><b>CONCLUSIONS:b> These findings suggest that the CEP may be a useful educational tool for use in the general population.<br />

Survey of canteens and food services in Victorian schools

<b>Objectiveb>: To examine the characteristics of food services in Victorian government primary and secondary schools. <br /><br /><b>Design and methodsb>: A cross-sectional postal survey of all high schools and a random sample of one quarter of primary school respondents in Victoria. A `School Food Services and Canteen' questionnaire was administered by mail to the principal of each school. <b><br /><br />Subjectsb>: Respondents included principals, canteen managers and home economics teachers from 150 primary and 208 secondary schools representing response rates of 48% and 67%, respectively. <b><br /><br />Main outcome measuresb>: Responses to closed questions about school canteen operating procedures, staff satisfaction, food policies and desired additional services. <b><br /><br />Data analysesb>: Frequency and cross-tabulation analyses and associated χ²-tests. <b><br /><br />Resultsb>: Most schools provided food services at lunchtime and morning recess but one-third provided food before school. Over 40% outsourced their food services, one-third utilised volunteer parents, few involved students in canteen operations. Half of the secondary schools had vending machines; one in five had three or more. Secondary school respondents were more dissatisfied with the nutritional quality of the food service, and expressed more interest in additional services than primary respondents. Schools with food policies wanted more service assistance and used volunteer parents, student and paid canteen managers more than schools without policies. <br /><br /><b>Conclusionb>: Most schools want to improve the nutritional quality of their food services, especially via school food policies. There is a major opportunity for professional organisations to advocate for the supply of healthier school foods.<br />