bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjusting for covariates on a slippery slope: linkage analysis of change over time
Authors: Rampersaud Evadnie , Allen Andrew , Li Yi-Ju , Shao Yujun , Bass Meredyth , Haynes Carol , Ashley-Koch Allison , Martin Eden R , Schmidt Silke , Hauser Elizabeth R 
Published: December 2003

Abstract
Background
We analyzed the Genetic Analysis Workshop 13 (GAW13) simulated data to contrast and compare different methods for the genetic linkage analysis of hypertension and change in blood pressure over time. We also examined methods for incorporating covariates into the linkage analysis. We used methods for quantitative trait loci (QTL) linkage analysis with and without covariates and affected sib-pair (ASP) analysis of hypertension followed by ordered subset analysis (OSA), using variables associated with change in blood pressure over time.

Results
Four of the five baseline genes and one of the three slope genes were not detected by any method using conventional criteria. OSA detected baseline gene b35 on chromosome 13 when using the slope in blood pressure to adjust for change over time. Slope gene s10 was detected by the ASP analysis and slope gene s11 was detected by QTL linkage analysis as well as by OSA analysis. Analysis of null chromosomes, i.e., chromosomes without genes, did not reveal significant increases in type I error. However, there were a number of genes indirectly related to blood pressure detected by a variety of methods.

Conclusions
We noted that there is no obvious first choice of analysis software for analyzing a complicated model, such as the one underlying the GAW13 simulated data. Inclusion of covariates and longitudinal data can improve localization of genes for complex traits but it is not always clear how best to do this. It remains a worthwhile task to apply several different approaches since one method is not always the best.
Genome-wide linkage scan on estimated breeding values for a quantitative trait
Authors: Zabaneh Delilah , Mackay Ian J 
Published: December 2003

Abstract
Background
A genome-wide linkage scan was performed on Replicate 1 of the simulated data for fasting triglyceride levels. The aim of this study was to implement mixed-model methodology to estimate breeding values for each individual for this trait and to assess the merit of these breeding values in linkage analysis. These breeding values utilize all the pedigree information, and the genetic and phenotypic correlations with other measured traits across the two cohorts. A genome-wide linkage scan was run on both the new breeding value traits and the original traits.

Results
Using breeding values, a maximum LOD of 7.78 was found on chromosome 5 at a position very close to a gene underlying the triglyceride levels. This effect was not detected using the original trait.

Conclusion
The results imply that estimating breeding values may be a suitable method of deriving traits for use in genome-wide scans.
Linkage analysis of the simulated data – evaluations and comparisons of methods
Authors: Biswas Swati , Papachristou Charalampos , Irwin Mark E , Lin Shili 
Published: December 2003

AbstractThe goal of this study is to evaluate, compare, and contrast several standard and new linkage analysis methods. First, we compare a recently proposed confidence set approach with MAPMAKER/SIBS. Then, we evaluate a new Bayesian approach that accounts for heterogeneity. Finally, the newly developed software SIMPLE is compared with GENEHUNTER. We apply these methods to several replicates of the Genetic Analysis Workshop 13 simulated data to assess their ability to detect the high blood pressure genes on chromosome 21, whose positions were known to us prior to the analyses. In contrast to the standard methods, most of the new approaches are able to identify at least one of the disease genes in all the replicates considered.
Segregation analysis comparing liability and quantitative trait models for hypertension using the Genetic Analysis Workshop 13 simulated data
Authors: Crockford GP , Bishop DT , Barrett JH 
Published: December 2003

AbstractDiscrete (qualitative) data segregation analysis may be performed assuming the liability model, which involves an underlying normally distributed quantitative phenotype. The appropriateness of the liability model for complex traits is unclear. The Genetic Analysis Workshop 13 simulated data provides measures on systolic blood pressure, a highly complex trait, which may be dichotomized into a discrete trait (hypertension). We perform segregation analysis under the liability model of hypertensive status as a qualitative trait and compare this with results using systolic blood pressure as a quantitative trait (without prior knowledge at that stage of the true underlying simulation model) using 1050 pedigrees ascertained from four replicates on the basis of at least one affected member. Both analyses identify models with major genes and polygenic components to explain the family aggregation of systolic blood pressure. Neither of the methods estimates the true parameters well (as the true model is considerably more complicated than those considered for the analysis), but both identified the most complicated model evaluated as the preferred model. Segregation analysis of complex diseases using relatively simple models is unlikely to provide accurate parameter estimates but is able to indicate major gene and/or polygenic components in familial aggregation of complex diseases.
Age-of-onset of hypertension vs. a single measurement of systolic blood pressure in a combined linkage and segregation analysis
Authors: Daw E Warwick , Liu Xiaoming , Wu Chih-Chieh 
Published: December 2003

Abstract
Background
Often, multiple measures of a trait are available in a genetic linkage analysis. We compare Monte Carlo Markov chain analysis of two very different measures of hypertension in the simulated Genetic Analysis Workshop 13 data to examine how choice of measure affects the results. The measures selected were age-of-onset of hypertension and systolic blood pressure at first visit.

Results
In combined segregation and linkage analysis of the complete pedigrees using the first replicate of the simulated data with missing values, we found that the age-of-onset analysis was better at identifying "slope" genes, while the systolic blood pressure analysis was better at identifying "baseline" genes.

Conclusion
Analysis of different trait measures may identify different trait-related genes. When linkage analysis is conducted on multiple trait measures, a linkage signal found for only one measure can represent a true trait locus.
Bivariate variance-component analysis, with application to systolic blood pressure and total cholesterol levels in the Framingham Heart Study
Authors: Cui Jisheng S , Sheffield Leslie J 
Published: December 2003

Abstract
Background
The correlations between systolic blood pressure (SBP) and total cholesterol levels (CHOL) might result from genetic or environmental factors that determine variation in the phenotypes and are shared by family members. Based on 330 nuclear families in the Framingham Heart Study, we used a multivariate normal model, implemented in the software FISHER, to estimate genetic and shared environmental components of variation and genetic and shared environmental correlation between the phenotypes. The natural logarithm of the phenotypes measured at the last visit in both Cohort 1 and 2 was used in the analyses. The antihypertensive treatment effect was corrected before adjustment of the systolic blood pressure for age, sex, and cohort.

Results
The univariate correlation coefficient was statistically significant for sibling pairs and parent-offspring pairs, but not significant for spouse pairs. In the bivariate analysis, the cross-trait correlation coefficients were not statistically significant for all relative pairs. The shared environmental correlation was statistically significant, but the genetic correlation was not significant.

Conclusion
There is no significant evidence for a close genetic correlation between systolic blood pressure and total cholesterol levels. However, some shared environmental factors may determine the variation of both phenotypes.
Using an age-at-onset phenotype with interval censoring to compare methods of segregation and linkage analysis in a candidate region for elevated systolic blood pressure
Authors: Kopciuk Karen A , Briollais Laurent , Demenais Florence , Bull Shelley B 
Published: December 2003

Abstract
Background
Genetic studies of complex disorders such as hypertension often utilize families selected for this outcome, usually with information obtained at a single time point. Since age-at-onset for diagnosed hypertension can vary substantially between individuals, a phenotype based on long-term follow up in unselected families can yield valuable insights into this disorder for the general population.

Methods
Genetic analyses were conducted using 2884 individuals from the largest 330 families of the Framingham Heart Study. A longitudinal phenotype was constructed using the age at an examination when systolic blood pressure (SBP) first exceeds 139 mm Hg. An interval for age-at-onset was created, since the exact time of onset was unknown. Time-fixed (sex, study cohort) and time-varying (body mass index, daily cigarette and alcohol consumption) explanatory variables were included.

Results
Segregation analysis for a major gene effect demonstrated that the major gene effect parameter was sensitive to the choice for age-at-onset. Linkage analyses for age-at-onset were conducted using 1537 individuals in 52 families. Evidence for putative genes identified on chromosome 17 in a previous linkage study using a quantitative SBP phenotype for these data was not confirmed.

Conclusions
Interval censoring for age-at-onset should not be ignored. Further research is needed to explain the inconsistent segregation results between the different age-at-onset models (regressive threshold and proportional hazards) as well as the inconsistent linkage results between the longitudinal phenotypes (age-at-onset and quantitative).
A cautionary note on the appropriateness of using a linkage resource for an association study
Authors: Allen-Brady Kristina , Farnham James M , Weiler Jeff , Camp Nicola J 
Published: December 2003

Abstract
Background
Utilizing a linkage resource for association analysis requires consideration both of the marker data used and correlations among relatives in pedigrees. We previously developed a method for association testing in pedigrees. We applied our method to 50 replicates of microsatellite data surrounding five genes involved in high-density lipoprotein (HDL) in the Genetic Analysis Workshop 13 (GAW13) simulated data and examined association with HDL as well as linkage disequilibrium (LD) between markers.

Results
Although no association was intentionally simulated, we found significant evidence of weak LD between microsatellite markers (flanking/~5 cM from the genes), in some but not all replicates. This level of LD compared well to that observed in the real GAW13 Framingham data. Only one region had sufficient replicates to assess power, and this was low (12.5–20.8%). More power was attained using all individuals and accounting for relationships, compared with one independent individual/pedigree, although this was not significant due to small sample sizes. Not accounting for relatedness inflated statistical significance (p < 0.0001).

Conclusion
A correction for dependence is necessary in association studies to avoid an inflation of significance probabilities. Our results further illustrate that use of microsatellite marker data is not an effective approach for association testing.
HDL cholesterol in females in the Framingham Heart Study is linked to a region of chromosome 2q
Authors: North Kari E , Martin Lisa J , Dyer Tom , Comuzzie Anthony G , Williams Jeff T 
Published: December 2003

Abstract
Background
Despite strong evidence for a genetic component to variation in high-density lipoprotein cholesterol levels (HDL-C), specific polymorphisms associated with normal variation in HDL-C have not been identified. It is known, however, that HDL-C levels are influenced in complex ways by factors related to age and sex. In this paper, we examined the evidence for age- and sex-specific linkage of HDL-C in a longitudinal sample of participants from the Framingham Heart Study.
To determine if aging could influence our ability to detect linkage, we explored the evidence for linkage of HDL-C at three time points, t1, t2, and t3, spaced approximately 8 years apart and corresponding respectively to visits 11, 15, and 20 for the original cohort and 1, 2, and 4 for the offspring and spouses. Additionally, to examine the effects of sex on linkage at each time point, we estimated the heritability and genetic correlation of HDL-C, performed linkage analysis of HDL-C, tested for genotype-by-sex interaction at a QTL, and performed linkage analysis of HDL-C in males and females separately.

Results and Conclusion
In women, we found evidence for a QTL on chromosome 2q influencing HDL-C variation. Although the QTL could be detected in the combined sample of males and females at the first time point, the linkage was not significant at subsequent time points.
Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock
Authors: Goscinski Gunilla , Lipcsey Miklos , Eriksson Mats , Larsson Anders , Tano Eva , Sjölin Jan 
Published: December 2003

Abstract
Introduction
Antibiotics used for treatment of severe bacterial infections have been shown to exert effects on the inflammatory response in addition to their antibacterial effects. The aim of the present study was to investigate whether the biological effects of endotoxin in a porcine model could be neutralized by tobramycin, and whether tobramycin or ceftazidime was able to modulate the inflammatory response.

Method
Thirteen piglets were subjected to endotoxin infusion at an initial rate of 4 μg/kg per hour, which was reduced to 1 μg/kg per hour after 30 min. Before endotoxin infusion, the animals received saline (n = 4), ceftazidime (n = 5), or tobramycin (n = 4) at clinically relevant doses. Physiological parameters were measured and blood samples were taken hourly for 6 hours for analysis of tumour necrosis factor-α, IL-6 and endotoxin concentrations.

Results
All of the animals exhibited physiological signs of severe sepsis without major differences between the groups. Plasma endotoxin concentration was stable after 1 hour. There were no differences in endotoxin concentration or initial tumour necrosis factor-α and IL-6 concentrations between the groups. At 6 hours the IL-6 concentration was significantly lower in the ceftazidime group than in the saline group (P < 0.05), and in both the ceftazidime and the tobramycin groups there were significantly greater reductions from peak values (P < 0.05).

Conclusion
There was no neutralization of the biological effects of endotoxin in this porcine model. However, our data indicate a possible anti-inflammatory effect exerted by both ceftazidime and tobramycin, which manifested as a significantly greater reduction in IL-6 in comparison with the untreated group.
Globalisation and mental disorders
Authors: Bhugra Dinesh , Mastrogianni Anastasia 
Published: December 2003

BackgroundGlobalisation is the process by which traditional boundaries of cultures are changing. Industrialisation, urbanisation and influence of the media are influencing idioms of distress across cultures.AimsTo discuss the role of globalisation, using the epidemiology, diagnosis, clinical presentation and treatment of depression across various cultures as an example.MethodRecent studies focusing on transcultural aspects of depression were reviewed and summarised.ResultsCultural, social and religious mores account for variations in the presentation of depression across cultures. Somatic symptoms are common presenting features throughout the world and may serve as cultural idioms of distress, but psychological symptoms can usually be found when probed. Feelings of guilt and suicide rates vary across cultures and depression may be underdiagnosed.ConclusionsTraining packages could enhance clinicians' cultural competency in multicultural settings. However, globalisation is likely to influence idioms of distress and pathways to care in ways that are difficult to predict.
Birth weight and later risk of depression in a national birth cohort
Authors: Gale Catharine R. , Martyn Christopher N. 
Published: December 2003

BackgroundLow birth weight increases the risk of childhood behavioural problems, but it is not clear whether poor foetal growth has a long-term influence on susceptibility to depression.AimsTo examine the relation between birth weight and risk of psychological distress and depression.MethodAt age 16 years 5187 participants in the 1970 British Cohort Study completed the 12-item General Health Questionnaire to assess psychological distress. At age 26 years 8292 participants completed the Malaise Inventory to assess depression and provided information about a history of depression.ResultsWomen whose birth weight was 3 kg had an increased risk of depression at age 26 years (OR=1.3; 95% CI 1.0–1.5) compared with those who weighed > 3.5 kg. Birth weight was not associated with a reported history of depression or with risk of psychological distress at age 16 years. In men there were no associations between any measurement and the full range of birth weight but, compared with men of normal birth weight, those born weighing $2.5 kg were more likely to be psychologically distressed at age 16 years (OR=l.6, 95% CI 1.1–2.5) and to report a history of depression at age 26 years (OR=l.6, 95% CI 1.1–2.3).ConclusionsImpaired neurodevelopment during foetal life may increase susceptibility to depression.
Ethnoepidemiology of postnatal depression
Authors: Lee Dominic T. S. , Yip Alexander S. K. , Leung Tony Y. S. , Chung Tony K. H. 
Published: December 2003

BackgroundAlthough there have been many studies of the biological and psychosocial causations of postnatal depression, studies of sociocultural risk factors are rare.AimsTo investigate the sociocultural risk factors of postnatal depression using ethnographically informed epidemiological methods.MethodAtotal of 959 women were assessed at their first ante-partum visit (baseline), in the third trimester, immediately after delivery, and 3 months post-partum. Six domains of risk factors were examined. The dependent variable was postnatal depression (as defined by the Edinburgh Postnatal Depression Scale) at 3 months post-partum.ResultsConflict with mother-in-law, marital dissatisfaction, past depression and antenatal depression independently predicted the occurrence of postnatal depression. The cultural practice of peiyue – a Chinese post-partum custom of mandated family support – was associated with better social support and a slightly lower risk of postnatal depression.ConclusionsSociocultural aspects of the immediate puerperium shape maternal emotional well-being. In-law conflict is an important source of household distress in many Asian societies. The findings have implications for clinical practice and future studies.
Early cognitive–behavioural therapy for post-traumatic stress symptoms after physical injury
Authors: Bisson Jonathan I. , Shepherd Jonathan P. , Joy Deborah , Probert Rachel , Newcombe Robert G. 
Published: December 2003

BackgroundEarly single-session psychological interventions, including psychological debriefing following trauma, have not been shown to reduce psychological distress. Longer early psychological interventions have shown some promise.AimsTo examine the efficacy of a four-session cognitive–behavioural intervention following physical injury.MethodA total of 152 patients attending an accident and emergency department displaying psychological distress following physical injury were randomised 1–3 weeks post-injury to a four-session cognitive–behavioural intervention that started 5–10 weeks after the injury or to no intervention and then followed up for 13 months.ResultsAt 13 months, the total Impact of Event Scale score was significantly more reduced in the intervention group (adjusted mean difference=8.4, 95% CI 2.4–14.36). Other differences were not statistically significant.ConclusionsAbrief cognitive–behavioural intervention reduces symptoms of post-traumatic stress disorder in individuals with physical injury who display initial distress.
Mental health survey of the adult population in Iran
Authors: Noorbala A. A. , Yazdi S. A. Bagheri , Yasamy M. T. , Mohammad K. 
Published: December 2003

BackgroundNo national data on the prevalence of mental disorders are available in Iran. Such information may be a prerequisite for efficient national mental health intervention.AimsTo determine the mental health status of a population sample aged 15 years and over.MethodThrough random cluster sampling, 35 014 individuals were selected and evaluated using the 28-item version of the General Health Questionnaire. A complementary semi-structured clinical interview was also undertaken to detect learning disability (‘mental retardation’), epilepsy and psychosis.ResultsAbout a fifth of the people in the study (25.9% of the women and 14.9% of the men) were detected as likely cases. The prevalence of mental disorders was 21.33% in rural areas and 20.9% in urban areas. Depression and anxiety symptoms were more prevalent than somatisation and social dysfunction. The interview of families by general practitioners revealed that the rates of learning disability epilepsy and psychosis were 1.4%, 1.2% and 0.6%, respectively Prevalence increased with age and was higher in the married, widowed, divorced, unemployed and retired people.ConclusionsPrevalence rates are comparable with international studies. There is a wide regional difference in the country, and women are at greater risk.
Evaluation of the Two-Way Communication Checklist as a clinical intervention
Authors: Van Os Jim , Altamura A. Carlo , Bobes Julio , Gerlach Jes , Hellewell Jonathan S. E. , Kasper Siegfried , Naber Dieter , Robert Philippe 
Published: December 2003

BackgroundPatients and doctors often have divergent views on care needs.AimsTo examine whether providing patients with an opportunity to identify and discuss their needs would improve communication and induce changes in care.MethodPatients with schizophrenia (n=134) were randomly allocated to either standard care or use of the Two-Way Communication Checklist (2-COM). Before seeing their clinician for a routine follow-up, participants in the active intervention group were given 2-COM, a list of 20 common needs, and told to indicate those areas they wanted to discuss with their doctor. Outcomes were assessed immediately and again after 6 weeks.ResultsUsing 2-COM induced a stable improvement of patient-reported quality of patient–doctor communication (B=0.33, P=0.031), and induced changes in management immediately after the intervention (OR=3.7, P=0.009; number needed to treat, 6). Treatment change was more likely in patients with more reported needs, and needs most likely to induce treatment change displayed stronger associations with non-medication than with medication changes.ConclusionsA simple intervention to aid people in discussion of their needs results in improved communication and changes in management.
A Novel and Highly Effective Halogenation of Alkanes with Halides on Oxidation with m-Chloroperbenzoic Acid: Looks Old, but New Reaction
Authors: Kojima Takahiko , Matsuo Hidenobu , Matsuda Yoshihisa 
Published: December 2003

Abstract
The combination of tetraalkylammonium halides (Cl−, Br−) and m-chloroperbenzoic acid in CH3CN effectively halogenated alkanes accompanied by the formation of alkyl m-chlorobenzoate; for which the alkyl halides were formed via a non-photoinduced radical mechanism and the esters were derived from a non-radical process and concomitant with the formation of corresponding trialkylamine.