Multivariate Association Analysis Research Articles

Narrative text analysis of Kentucky tractor fatality reports

Narrative information in fatality investigation reports contains data elements not routinely analyzed with coded occupational injury surveillance data. A narrative text analysis of 69 Kentucky Fatality Assessment and Control Evaluation (FACE) agricultural tractor fatality reports from 1994 to 2004 was performed. The FACE reports were developed using the National Institute for Occupational Safety and Health, Division of Safety Research-recommended FACE report format that incorporates Haddon's matrix. Haddon's matrix separates the fatal incident into three event phases and is used to develop points of intervention based on human, organizational, and environmental factors. A multivariate logistic regression analysis for association between identified exposure variables and the outcomes of interest was undertaken. The operation of a tractor with an attached bucket, muddy terrain, and being thrown from the tractor were independent risk factors for being declared “dead at the scene”. A tractor rollover and operation of a tractor on a slope were independent risk factors for being “crushed” by a tractor. Narrative text analysis of FACE fatality investigation reports is a valuable tool for the identification of additional factors contributing to tractor fatalities that can inform farm safety training, identify new areas for agricultural interventions, and support the development of new agricultural engineering strategies.

Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C‐related cirrhosis

Chronic hepatitis C can result in fatty changes in the liver. Previous studies have suggested that hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus (HCV) infection. The authors sought to determine whether hepatic steatosis is associated with hepatocellular carcinoma (HCC) in a cohort of patients with hepatitis C-related cirrhosis. The authors retrospectively identified 94 consecutive patients with hepatitis C cirrhosis who underwent liver transplantation from 1992 to 2005 and had pathology available for review. Of these, 32 had evidence of HCC, and 62 had no HCC on explant histology. All explant specimens were graded again for steatosis by a single, blinded pathologist. Steatosis, age, sex, body mass index, HCV RNA, HCV genotype, Model for End-Stage Liver Disease (MELD) score, chronic alcohol use, and diabetes were examined in univariate and multivariate analyses for association with HCC. In total, 69% of patients in the HCC group and 50% of patients in the control group had evidence of steatosis (1+) on histology. Odds ratios for the development of HCC for each grade of steatosis compared with grade 0 were as follows: grade 1 (1.61 [0.6-4.3]), grade 2 (3.68 [1.1-12.8]), and grade 3 or 4 (8.02 [0.6-108.3]) (P = .03 for the trend). In univariate analysis, there was a significant association between increasing steatosis grade (P = .03), older age (56 years vs 49 years; P < .02), higher aspartate aminotransferase (122.5 U/L vs 91.5 U/L; P = .005), higher alanine aminotransferase (95.8 U/L vs 57.2 U/L; P = .002), higher alpha-fetoprotein (113.5 ng/mL vs 17.8 ng/mL; P < .001), lower median HCV RNA (239,000 IU/mL vs 496,500 IU/mL; P = .02), higher biologic MELD score (21.8 vs 20.3; P = .03), and risk of HCC. In multivariate analysis, age (P = .02), AFP (P = .007), and steatosis (P = .045) were significantly associated with HCC. In patients with HCV-related cirrhosis, the presence of hepatic steatosis is independently associated with the development of hepatocellular carcinoma. These findings suggest that steatosis poses an additional risk for HCC and that increased vigilance should be practiced in surveillance of persons with both HCV and steatosis.

Appraised leadership styles, psychosocial work factors, and musculoskeletal pain among public employees

The main aim of this study was to explore the associations between appraised leadership styles, psychosocial work factors and musculoskeletal pain among subordinates in four different public service sectors from an epidemiological perspective. A cross-sectional questionnaire study was conducted; data from 2,403 public sector employees in subordinate positions (86% women) were analysed. The appraised leadership styles were measured through items from a modified version of the CPE questionnaire (C change, P production/structure, E employee/relation). The structure validity of the CPE-model was examined by principal component analysis (PCA). Univariate and multivariate analyses of associations between levels of musculoskeletal pain and appraised leadership styles and with psychosocial work factors were conducted. Odds ratios (ORs) with confidence intervals (CIs) of 95% were used as a measure of associations. There were small variations in the appraisals of the immediate manager among the subordinates. However, the associations between musculoskeletal pain and leadership styles varied according to sector. Poor appraisals (low scores) on "change" and "employee relation" dimensions were associated with high levels of musculoskeletal pain in two sectors: home and health care services. In the domestic catering services, poor appraisals of managers in the "production/structure" dimension had the strongest association with high levels of pain. In general, poor appraisals of the "change" dimension was most strongly associated with high levels of musculoskeletal pain. "High work demands" had the strongest association with high levels of pain, particularly among the men. Poor appraisals of managers and their leadership styles were associated with high levels of musculoskeletal pain among both female and male subordinates in different public service sectors. There is therefore a great need of further studies of the mechanisms behind the relationships between the leadership styles and their impact on health among the genders.

Genetic Covariation between Event-Related Potential (ERP) and Behavioral Non-ERP Measures of Working-Memory, Processing Speed, and IQ

The aim of this study was to identify genetic covariants for fundamental measures of brain function (event-related potentials (ERPs): P300 latency and slow wave amplitude recorded in a working-memory task) and more complex cognitive measures (behavioral non-ERP measures: working-memory performance, information processing speed, IQ). Data were collected from 252 monozygotic and 297 dizygotic twin pairs aged 16. Multivariate modeling identified two independent genetic factors associated with processing speed that also influenced working-memory performance (one reflected the duration of neural activity required to evaluate target information, the other reflected more general cognitive and speed-related abilities). However, the allocation of neural resources, as assessed by ERP slow wave amplitude measures, was not associated with the other cognitive measures investigated. Thus, of the ERP measures examined, P300 latency, but not slow wave amplitude, may be an informative measure to include (i.e., with working-memory performance) in future multivariate linkage and association analyses of cognitive function.

Airborne particle deposition onto the ocular surface

Eye irritation is one of the most frequently reported symptoms in relation to working in office-like environments. So far, no consistent association has been found between concentration of airborne particles and prevalence of eye irritation. External physical factors not hitherto considered could have a large influence on particle deposition velocity onto the ocular surface. This may have obscured the role airborne particles play. Based on previously published semi-empirical models, the paper describes the influence of turbulence, gravitational settling, electrical fields, and thermophoresis on deposition velocity. A probabilistic approach was used to determine percentile ranges in deposition velocity when the magnitude of these parameters varied within typical ranges. The calculations suggest that differences in external factors other than particle size may cause differences in the deposition velocity of one order of magnitude or more. Studies trying to find associations between airborne particle concentration levels and eye irritation should take into consideration the influence of external physical factors on deposition velocity. External physical factors other than concentration are likely to have a large influence on the deposition rate of airborne particles onto the ocular surface. Thus, future studies on associations between airborne particle levels and eye symptoms should only be conducted if particle concentration measurements are suitably size resolved. Other relevant external physical factors should also be assessed and included in a multivariate analysis of exposure-response associations.

Early outcomes of endovascular versus open abdominal aortic aneurysm repair in the National Surgical Quality Improvement Program–Private Sector (NSQIP–PS)

There remains no consensus on the appropriate application of endovascular abdominal aortic aneurysm repair (EVAR). Information from administrative databases, industry-sponsored trials, and single institutions has inherent deficiencies. This study was designed to compare early outcomes of open (OPEN) versus EVAR in a contemporary (2000 to 2003) large, multicenter prospective cohort. Fourteen academic medical centers contributed data to the National Surgical Quality Improvement Program-Private Sector (NSQIP-PS), which ensures uniform, comprehensive, prospective, and previously validated data entry by trained, independent nurse reviewers. A battery of clinical and demographic features was assessed with multivariate analysis for association with the principal study end points of 30-day operative mortality and morbidity. One thousand forty-two patients underwent elective infrarenal abdominal aortic aneurysm (AAA) repairs: 460 EVAR and 582 OPEN. EVAR patients were older (74 vs 71 years, P < .0001), included more men (84.6% vs 79.6%, P < .05), and had a higher incidence of chronic obstructive pulmonary disease (25.4% vs 17.9%, P < .01). EVAR resulted in significantly reduced overall morbidity (24% vs 35%, P < .0001) and hospital stay (4 vs 9 days, P < .0001). Cardiopulmonary and renal function-related comorbidities had the expected significant impact on mortality for both procedures at univariate analysis ( P < .05). While crude mortality rates between EVAR and OPEN did not differ significantly (2.8% vs 4.0%) ( P = 0.32). After multivariate analysis, correlates of operative mortality included OPEN (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.03 to 5.78; P < .05), advanced age (OR, 1.11; P < .001), history of angina (OR, 5.54; P < .01), poor functional status (OR, 5.78; P < .001), history of weight loss (OR, 7.42; P < .01), and preoperative dialysis (OR, 51.4; P < .0001). EVAR also compared favorably to OPEN (OR, 2.14; 95% CI, 1.58 to 2.89; P < .0001) for overall morbidity. Significant morbidity accompanies AAA repair, even at major academic medical centers. These data strongly endorse EVAR as the preferred approach in the presence of significant cardiopulmonary or renal comorbidities, or poor preoperative functional status.

Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity

Objective This study was undertaken to evaluate the effect of exposure to multiple antenatal steroid courses on short-term neonatal morbidity and 2-year infant neurodevelopmental outcome. Study design This was a prospective observational study of 201 preterm singleton infants who received 1 or more courses of corticosteroids to prevent complications of prematurity and were delivered between 24 and 34 weeks' gestation at a single institution. Neurodevelopmental outcome of the infants was evaluated at 2 years corrected age. Logistic regression analysis was used to perform multivariate analyses of associations and trends. Results One hundred thirty-eight subjects (68.7%) received at least 1 complete course of betamethasone, whereas 63 (31.3%) patients were treated with dexamethasone. The prevalence of multiple steroid doses exposure was 26.8% (37/138) in betamethasone and 52.4% (33/63) in dexamethasone group. The prevalence of infant leukomalacia, including both prolonged echogenicity and cystic leukomalacia, was 25.9% (34/131) after a complete corticosteroid course, 40% (6/15) after 1, 42.3% (12/28) after 2, and 44.4% (12/27) after more than 2 additional courses, respectively (adjusted P for trend = .011). In the same categories of steroid exposure, the corresponding prevalences of 2-year infant neurodevelopmental abnormalities were 18% (20/111), 21.4% (3/14), 29.2% (7/24), and 34.8% (8/23), respectively (adjusted P for trend = .038). Multivariate study of first grade interaction suggested that the risk of leukomalacia and 2-year infant neurodevelopmental abnormalities associated with multiple doses exposure was confined to dexamethasone. In fact, compared with betamethasone, exposure to multiple doses of dexamethasone was associated with an increased risk of leukomalacia (19/33 compared with 11/37; odds ratio [OR] = 3.21, 95% CI = 1.07-9.77) and overall 2-year infant neurodevelopmental abnormalities (12/28 compared with 6/35; OR = 3.63, 95% CI = 1.03-13.58). Conclusion In this study, multiple antenatal courses of dexamethasone but not betamethasone were associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities.

Characteristics of treated hypertension in incident hemodialysis and peritoneal dialysis patients

Background: The treatment of hypertension in dialysis patients is prevalent and poorly characterized. β-Blockers and calcium channel blockers (CCBs) have been associated with reduced all-cause and cardiovascular mortality. This study describes the treatment of hypertension and assesses the association between mortality and class of antihypertensive medication among a cohort of dialysis patients. Methods: The US Renal Data System (USRDS) Dialysis Morbidity and Mortality Study Wave II cohort was analyzed. A total of 2,877 patients initiating hemodialysis or peritoneal dialysis in 1996 or 1997 and treated with antihypertensives were included in this analysis. Vital status was followed until November 2000. Results: Calcium channel blockers were prescribed to 70.3% of patients. Only 31.5% and 27.0% of patients with cardiovascular disease were prescribed angiotensin-converting enzyme inhibitors and β-blockers, respectively. Mono-, double-, triple-, and more than triple-therapy were reported in 48.0%, 36.1%, 13.2%, and 2.7% of the cohort, respectively. In multivariable, fully adjusted models, no individual class of antihypertensives was associated with changes in all-cause mortality. In all patients, nondihydropyridine CCBs (non-DHP CCBs) were associated with a reduced risk of cardiovascular death (hazard ratio, 0.78; 95% confidence interval, 0.62 to 0.97) and among end-stage renal disease patients with preexisting cardiovascular disease, dihydropyridine CCBs (DHP CCBs) and non-DHP CCBs were associated with reduced risk of all-cause and cardiovascular mortality. Conclusion: Calcium channel blocker use is widespread among hypertensive dialysis patients. Antihypertensive prescription patterns suggest a lack of consensus regarding treatment of hypertension. Multivariable analysis of associations between antihypertensive class and mortality reveals results of uncertain clinical significance. Hypertension treatment trials in dialysis patients should be performed to appropriately inform treatment decisions.

Effects of dopamine receptor D4 variation on alcohol and tobacco use and on novelty seeking: multivariate linkage and association analysis.

The dopamine D4 receptor gene contains a polymorphic sequence consisting of a variable number of 48-base-pair (bp) repeats, and there have been a number of reports that this polymorphism is associated with variation in novelty seeking or in substance abuse and addictive behaviors. In this study we have assessed the linkage and association of DRD4 genotype with novelty seeking, alcohol use, and smoking in a sample of 377 dizygotic twin pairs and 15 single twins recruited from the Australian Twin Registry (ATR). We found no evidence of linkage or association of the DRD4 locus with any of the phenotypes. We made use of repeated measures for some phenotypes to increase power by multivariate genetic analysis, but allelic effects were still non-significant. Specifically, it has been suggested that the DRD4 7-repeat allele is associated with increased novelty seeking in males but we found no evidence for this, despite considerable power to do so. We conclude that DRD4 variation does not have an effect on use of alcohol and the problems that arise from it, on smoking, or on novelty seeking behavior.

Univariate and multivariate family-based association analysis of the IL-13 ARG130GLN polymorphism in the Childhood Asthma Management Program.

Interleukin 13 (IL-13) has been demonstrated to have a crucial role in animal models of allergy and asthma. In human case-control genetic-association studies, the Arg130Gln polymorphism has been associated with elevated total serum IgE and an asthma diagnosis in atopic and nonatopic individuals (Graves et al. [2000] J. Allergy Clin. Immunol. 105:506-513; Heinzmann et al. [2000] Hum. Mol. Genet. 9:549-559). To apply family-based association methods, we obtained DNA samples from 685 asthmatic children from 640 sibships and their parents in the Childhood Asthma Management Program (CAMP). Six hundred and sixty-six asthmatic children had complete phenotypic information and were used for this analysis. We performed quantitative association analysis using the transmission disequilibrium test (TDT) on 22 individual phenotypes and 5 grouped phenotypes relating to allergy, airway responsiveness, pulmonary function, bronchodilator responsiveness, and asthma severity, using genotypes at the Arg130Gln polymorphism of the IL-13 gene. A positive association was obtained between Arg130Gln and a grouped phenotype of allergy (consisting of the individual phenotypes of eosinophils, IgE, and positive skin tests), using FBAT-GEE, a multivariate extension of the family-based association test (Lange et al. [2002] Biostatistics 1:1-15). The three phenotypes were then evaluated individually and revealed a significant association between total eosinophil count and the Arg130Gln locus; there was a trend for association between total IgE and the Arg130Gln polymorphism. The Arg130Gln polymorphism is associated with an elevated eosinophil count as well as with a grouped allergy phenotype, in children with mild to moderate asthma. No evidence for association was found between Arg130Gln and airway responsiveness, asthma diagnosis, or asthma severity.

Gender differences in the effects from working conditions on mental health: a 4-year follow-up.

The overall aim was to examine how working conditions in 1993 influenced the occurrence of poor mental health in 1997 among women and men from the general population. Also, the relative importance of other living conditions in relation to poor mental health in 1997 was examined. A sample from the general Swedish population (originally examined in 1969) was followed up in 1993 and 1997. Data from these follow-ups were analysed, and both bivariate and multivariate analyses of associations between occupational and non-occupational conditions in 1993 and poor mental health in 1997 -- defined as sub-clinical depression, reduced psychological well-being and high alcohol consumption -- were performed. Several occupational risk indicators were identified for poor mental health among women, especially sub-clinical depression and high alcohol consumption. Occupational factors such as shift work, job strain, no education at the employer's expense, low occupational pride, low stimulation at work and poor social support were related to poor mental health among women. For poor mental health among men, mainly sub-clinical depression, shift work and low occupational pride were identified as risk indicators. Non-occupational factors related to poor mental health among women were poor quality of social contacts, demanding life events, physical inactivity, high perceived physical load outside work and inadequate coping strategies. Among men, smoking and inadequate coping strategies were related to poor mental health. The difference between women and men, regarding the numbers of identified occupational and non-occupational risk indicators, may partly be explained by the gender-segregated labour market, and partly by other explanations. In our study, we have not succeeded in collecting the relevant information about occupational conditions that is important for men's mental health.

Increasing representation of localized dung beetles across a chronosequence of regenerating vegetation and natural dune forest in South Africa

AbstractAim Species assemblages with high proportions of localized taxa occur in regional islands with a history of strong eco‐climatic separation from adjacent systems. Current disturbance in such islands of relictualism or endemism disrupts the distinctive local character in favour of regionally distributed taxa with a wider range of tolerances. However, rehabilitation of the system should restore the localized biota. Thus, we used biogeographical composition to assess progress towards restoration of the dung beetle fauna associated with such an island of endemism following dredge‐mining.Location The study was conducted in natural coastal dune forest and a 23‐year chronosequence of regenerating dune vegetation in the Maputaland centre of endemism, KwaZulu‐Natal, South Africa.Methods Dung beetles were trapped in eight stands of regenerating vegetation of different ages (&lt; 1 year to ~21 years) and in four stands of natural dune forest with differing ecological characteristics defined by measurements of vegetative physiognomy and microclimate. Species groups defined from multivariate analysis of biogeographical distribution patterns and vegetation associations were used to demonstrate quantitative compositional changes in the dung beetle assemblages across the chronosequence to natural forest.Results Three biogeographical groups were defined. One group comprised species widespread in southern Africa or both southern and east Africa. The other two groups were endemic, one to the east coast and the other to Maputaland. There was a general trend from dominance by regionally distributed dung beetle taxa to dominance by locally distributed taxa across the chronosequence of regenerating vegetation from grassland, to open Acacia karroo thicket, to dense A. karroo‐dominated woodland. However, this trend was linked closely to the relative physiognomic and microclimatic similarity between the regenerating vegetation and natural forest. Thus, proportions of locally distributed taxa were lower in older chronosequence woodland (~18–~21 years) with its low canopy cover and open understorey than in dense early chronosequence woodland (~9–~12 years), which is physiognomically and microclimatically closer to species‐diverse natural forest with its dense canopy and understorey. Overall, the present dung beetle community comprises five species groups. Single widespread (21 spp.) and endemic groups (14 spp.) showed similar patterns of association with early chronosequence grassland and open thicket stands. A single widespread (3 spp.) and two endemic shade‐associated groups (3 and 11 spp.) showed differing patterns of association centred, respectively, in late chronosequence woodland, natural forest, or all shaded stands.Main conclusions At 23 years, vegetative regeneration is still at an early stage, but abundant activity of most, although not all species recorded in natural forest, is recovered with the closure of the woodland canopy at ~9 years. Compositional differences with respect to natural forest vary closely with vegetative physiognomy and its effect on the microclimate. Therefore, full compositional recovery is dependent on the re‐establishment of natural forest physiognomy and microclimate.

Physical-chemical influences on vernal zooplankton community structure in small lakes and wetlands of Wisconsin, U.S.A.

We sampled zooplankton communities from 54 small water bodies distributed throughout Wisconsin to evaluate whether a ‘snap-shot’ of zooplankton community structure during early spring could be used for the purpose of differentiating lakes from wetlands. We collected a single set of zooplankton and water chemistry data during a one-month time window (synchronized from south to north across the state) from an open water site in each basin as a means to minimize and standardize sampling effort and to minimize cascading effects arising from predator–prey interactions with resident and immigrant aquatic insect communities. We identified 53 taxa of zooplankton from 54 sites sampled across Wisconsin. There was an average of 6.83 taxa per site. The zooplankton species were distributed with a great deal of independence. We did not detect significant correlations between number of taxa and geographic region or waterbody size. There was a significant inverse correlation between number of taxa and the concentration of calcium ion, alkalinity and conductivity. One pair of taxa, Lynceus brachyurus and Chaoborus americanus, showed a significant difference in average duration of sites of their respective occurrence. All other pairs of taxa had no significant difference in average latitude, waterbody surface area, total phosphorus, total Kjeldahl nitrogen, alkalinity, conductivity, calcium ion, sulfate, nitrate, silicate or chloride. Taxa were distributed at random among the sites – there were no statistically significant pairs of taxa occurring together or avoiding each other. Multivariate analysis of zooplankton associations showed no evidence of distinct associations that could be used to distinguish lakes from wetlands. Zooplankton community structure appears to be a poor tool for distinguishing between lakes and wetlands, especially at the relatively large scale of Wisconsin (dimension of about 500 km). The data suggest that a small body of water in Wisconsin could be classified as a wetland if it persists in the spring and summer for only about 4 months, and if it is inhabited by Lynceus brachyurus, Eubranchipus bundyi, and if Chaoborus americanus and Chydorus brevilabris are absent.

A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory.

Cloninger (Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987: 236: 410-416) proposed three basic personality dimensions for temperament: novelty seeking, harm avoidance, and reward dependence. He suggested that novelty seeking primarily utilized dopamine pathways, harm avoidance utilized serotonin pathways, and reward dependence utilized norepinephrine pathways. Subsequently, one additional temperament dimension (persistence) and three character dimensions (cooperativeness, self-directedness, and self-transcendence) were added to form the temperament and character inventory (TCI). We have utilized a previously described multivariate analysis technique (Comings DE, Gade-Andavolu R, Gonzalez N et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196; Comings DD, Gade-Andavolu R, Gonzalez N et al. Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder. Clin Genet 2000: in press) to examine the relative role of 59 candidate genes in the seven TCI traits and test the hypothesis that specific personality traits were associated with specific genes. While there was some tendency for this to be true, a more important trend was the involvement of different ratios of functionally related groups of genes, and of different genotypes of the same genes, for different traits.

Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder.

In a previous study (Comings DE et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196) we examined the role of 20 dopamine, serotonin and norepinephrine genes in attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), using a multivariate analysis of associations (MAA) technique. We have now brought the total number of genes examined to 42 by adding an additional 22 candidate genes. These results indicate that even with the inclusion of these additional genes the noradrenergic genes still played a greater role in ADHD than any other group. Six other neurotransmitter genes were included in the regression equation - cholinergic, nicotinic, alpha 4 receptor (CHNRA4), adenosine A2A receptor (ADOA2A), nitric oxide synthase (NOS3), NMDAR1, GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P-450), ESR1, and INS (p = 0.005). This is consistent with our prior studies indicating a role of the androgen receptor (AR) gene in a range of externalizing behavors. We propose that the MAA technique, by focusing on the additive effect of multiple genes and on the cummulative effect of functionally related groups of genes, provides a powerful approach to the dissection of the genetic basis of polygenic disorders.

Reward deficiency syndrome: genetic aspects of behavioral disorders

The dopaminergic and opioidergic reward pathways of the brain are critical for survival since they provide the pleasure drives for eating, love and reproduction; these are called 'natural rewards' and involve the release of dopamine in the nucleus accumbens and frontal lobes. However, the same release of dopamine and production of sensations of pleasure can be produced by 'unnatural rewards' such as alcohol, cocaine, methamphetamine, heroin, nicotine, marijuana, and other drugs, and by compulsive activities such as gambling, eating, and sex, and by risk taking behaviors. Since only a minority of individuals become addicted to these compounds or behaviors, it is reasonable to ask what factors distinguish those who do become addicted from those who do not. It has usually been assumed that these behaviors are entirely voluntary and that environmental factors play the major role; however, since all of these behaviors have a significant genetic component, the presence of one or more variant genes presumably act as risk factors for these behaviors. Since the primary neurotransmitter of the reward pathway is dopamine, genes for dopamine synthesis, degradation, receptors, and transporters are reasonable candidates. However, serotonin, norepinephrine, GABA, opioid, and cannabinoid neurons all modify dopamine metabolism and dopamine neurons. We have proposed that defects in various combinations of the genes for these neurotransmitters result in a Reward Deficiency Syndrome (RDS) and that such individuals are at risk for abuse of the unnatural rewards. Because of its importance, the gene for the [figure: see text] dopamine D2 receptor was a major candidate gene. Studies in the past decade have shown that in various subject groups the Taq I A1 allele of the DRD2 gene is associated with alcoholism, drug abuse, smoking, obesity, compulsive gambling, and several personality traits. A range of other dopamine, opioid, cannabinoid, norepinephrine, and related genes have since been added to the list. Like other behavioral disorders, these are polygenically inherited and each gene accounts for only a small per cent of the variance. Techniques such as the Multivariate Analysis of Associations, which simultaneously examine the contribution of multiple genes, hold promise for understanding the genetic make up of polygenic disorders.

A longitudinal study of chronic disease and depressive symptoms in a community sample of older people

Previous research on the association between illness and depression in older people has relied on self-reported diagnoses with their inherent limitations in scope and reliability. This longitudinal study examined the association between depressive symptoms and medically-diagnosed chronic physical and neurodegenerative diseases and disability in community-living older people. In 1992, a random sample of 299 people aged 75 years and older underwent a clinical interview and medical examination by a physician experienced in geriatric medicine. This was repeated in 1995. The examination included diagnoses of chronic active physical illness, a standardized neurological examination, an assessment of functional disability and an abbreviated neuropsychological assessment. Depressive symptoms were assessed by the Centre for Epidemiological Studies - Depression scale. Multivariate analyses of concurrent associations, longitudinal associations and the impact of incident disease showed very few independent connections between individual diseases or the total burden of disease and depressive symptoms. However, in every circumstance, disability had a marked independent impact on depressive symptoms. Insofar as the diseases examined in this study are concerned, the association between physical disease and depressive symptoms in older people appears to be mediated through disability; disease may or may not result in disability but disability is likely to lead to increased depressive symptoms.

Association of syncytium-inducing phenotype of HIV-1 with CD4 cell count, viral load and sociodemographic characteristics.

To study whether syncytium-inducing (SI)/non-SI (NSI) phenotype of HIV-1 is associated with CD4+ lymphocyte count, plasma HIV RNA level, clinical stage and sociodemographic characteristics in antiretroviral-naive HIV-1-infected patients. Cross-sectional analysis of single centre cohort study data. SI/NSI phenotype was determined using a cocultivation assay using patients' peripheral blood mononuclear cells and MT2 cells. Standard procedures were used for CD4+ cell counts and viral load measurements in plasma. Univariate and multivariate analyses of association of CD4+ cell counts, viral load, clinical stage, age, sex and mode of HIV transmission were performed. In univariate analysis, SI phenotype was significantly associated with lower CD4+ cell counts, higher HIV RNA plasma levels, symptomatic HIV disease, male sex and age 32-36 years (middle tercile). In multivariate analysis, only lower CD4+ cell counts were associated with SI phenotype (odds ratio per increase of 100 x 10(6)/l, 0.54; 95% confidence interval, 0.38-0.78). HIV-1 SI phenotype was associated with lower CD4+ cell counts but not with higher plasma viral load, clinical stage or sociodemographic variables.

Trillion virion delay: time from testing positive for HIV to presentation for primary care.

Human immunodeficiency virus (HIV)-infected individuals' initial presentation to medical care frequently occurs at a point of advanced immunosuppression. To investigate the time between HIV testing and presentation to primary care. Also to examine factors associated with delayed presentation. One hundred eighty-nine consecutive outpatients without prior primary care for HIV infection were assessed at 2 urban hospitals: Boston City Hospital, Boston, Mass, and Rhode Island Hospital, Providence. Sociodemographics, alcohol and drug use, social support, sexual beliefs and practices, and HIV testing issues were examined in bivariate and multivariate analyses for association with delay in presentation to primary care after positive test results for HIV. Of 189 patients, 74 (39%) delayed seeking primary care for more than 1 year, 61 (32%) delayed for more than 2 years, and 35 (18%) for more than 5 years after an initial positive HIV serologic evaluation. The median CD4+ cell count of subjects was 0.28 x 10(9)/L (range, 0.001-1.71 x 10(9)/L). In multiple linear regression analysis the following characteristics were found to be associated with delayed presentation to primary care after HIV testing: history of injection drug use (P<.001); not having a living mother (P=.01); not having a spouse or partner (P=.08); not being aware of HIV risk before testing (P<.001); and being notified of HIV status by mail or telephone (P=.002). An interaction effect between sex and screening for alcohol abuse was significant (P=.03) and suggested longer delays for men with positive screening test results (CAGE [an alcoholism screening questionnaire containing 4 structured questions], 2+) compared with men without positive screening test results or women. Patients with positive HIV test results often delay for more than a year before establishing primary medical care. Information readily available at the time of HIV testing concerning substance abuse, social support, and awareness of personal HIV risk status is useful in identifying patients who are at high risk of not linking with primary care. Patients who were notified of their HIV status by mail or telephone delayed considerably longer than those notified in person. Efforts to ensure primary care linkage at the time of notification of positive HIV serostatus are necessary to maximize benefits for both individual and public health and should be an explicit task of posttest counseling.

Appraising Science Career Interests in Adolescent Girls and Boys

Science career choice is partly determined by precursors such as enrollment in science and mathematics courses, which are, in turn, determined by factors such as attitudes toward science, participation in science activities, and science career preference. Participants were 1,501 students, Grades 4 through 10, from a large, national intervention study. Independent variables were gender and grade. Dependent variables measured attitude, activities, and career preference. Multivariate, univariate, and discriminant analysis and chi-square tests of association were used. Girls were less likely than boys to see science as a male activity or to believe they had not received serious attention from their science teachers. In contrast, girls were less likely than boys to see science as a fun puzzle to be solved. On three out of four measures of interest in Realistic and Investigative careers (Holland, 1997), girls showed less interest than boys. There were no gender differences for science activities and no gender-by-grade interaction effects. Results confirm the complex nature of attraction to a career in science and shed some light on differences between boys and girls in the understructure of science career interest.