Evidence for linkage by transmission disequilibrium test analysis of a chromosome 22 microsatellite marker D22S278 and bipolar disorder in a Palestinian Arab population

A number of linkage studies suggest a schizophrenia susceptibility locus on chromosome 22, particularly with microsatellite marker D22S278 (22q12). In addition to some evidence for linkage to schizophrenia in this region, linkage to bipolar disorder using this marker has also been reported. We tested a group of 60 Bipolar I triads and an expanded group of 79 Bipolar I and Bipolar II triads recruited from a Palestinian Arab population for linkage with the D22S278 marker. Significant linkage was observed using the extended transmission disequilibrium test for multiallelic markers (ETDT) for both Bipolar I (P = 0.031) and the expanded group of Bipolar I and Bipolar II (P = 0.041). These weakly positive results are at least consistent with the hypothesis that this region of chromosome 22 might harbor a susceptibility locus for both major psychoses and should be considered for more intensive study. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:836-838, 2000.     

Dysfunctional regulation of alphaCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat

Syntaxin 1B and alphaCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. alphaCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP-induced expression in the aged rats. Dendritic alphaCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and alphaCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.     

Understanding illness: using drawings as a research method

Visual methodologies are becoming more evident in social research. These methodologies encompass media such as film, video, still photography, electronic visual media, and material artifacts. In this article, the author examines the use of drawings as a research tool used as an adjunct to other social research methods. Using examples from two studies, she illustrates how drawings can be used to explore the ways in which people understand illness conditions. She argues that the act of drawing necessitates knowledge production, with a visual product as its outcome. Although the examples presented in this article are limited to illness conditions, she argues that drawings offer a rich and insightful research method to explore how people make sense of their world.     

No evidence for linkage between COMT and schizophrenia in a French population

Catechol-O-methyltransferase is a candidate in the predisposition to schizophrenia both because of its function and the position of its gene. A multipoint non-parametric linkage analysis and a transmission disequilibrium test were performed on 42 multiplex families genotyped for Pml I and Bcl I polymorphisms using two definitions of the affected phenotype. Neither linkage nor preferential transmission of any allele or haplotype was detected, failing to replicate previous positive findings.     

Rapport and respect: negotiating ethical relations between researcher and participant

Qualitative research is largely dependent on building good interpersonal relations between researcher and participant. This is necessary for generating rich data, while at the same time ensuring respect is maintained between researcher and participant. We argue for a better understanding of researcher–participant relations in research practice. Codes of ethics, although important, do not address these kinds of ethical challenges. Negotiating the ethical relations between researcher and participant is paramount in maintaining ethical rigour in qualitative research. In this paper we propose concepts that can assist in understanding how the ethics of research relations are negotiated in practice; the ‘zone of the untouchable’ from the Danish philosopher, Løgstrup, is combined with the notion of ‘ethical mindfulness’. We argue how and why these concepts in tandem can heighten awareness and offer ways to address the ethically important moments in research.     

Analysis of nasopharyngeal carcinoma risk factors with Bayesian networks

Objectives

We propose a new graphical framework for extracting the relevant dietary, social and environmental risk factors that are associated with an increased risk of nasopharyngeal carcinoma (NPC) on a case-control epidemiologic study that consists of 1289 subjects and 150 risk factors.

Methods

This framework builds on the use of Bayesian networks (BNs) for representing statistical dependencies between the random variables. We discuss a novel constraint-based procedure, called Hybrid Parents and Children (HPC), that builds recursively a local graph that includes all the relevant features statistically associated to the NPC, without having to find the whole BN first. The local graph is afterwards directed by the domain expert according to his knowledge. It provides a statistical profile of the recruited population, and meanwhile helps identify the risk factors associated to NPC.

Results

Extensive experiments on synthetic data sampled from known BNs show that the HPC outperforms state-of-the-art algorithms that appeared in the recent literature. From a biological perspective, the present study confirms that chemical products, pesticides and domestic fume intake from incomplete combustion of coal and wood are significantly associated with NPC risk. These results suggest that industrial workers are often exposed to noxious chemicals and poisonous substances that are used in the course of manufacturing. This study also supports previous findings that the consumption of a number of preserved food items, like house made proteins and sheep fat, are a major risk factor for NPC.

Conclusion

BNs are valuable data mining tools for the analysis of epidemiologic data. They can explicitly combine both expert knowledge from the field and information inferred from the data. These techniques therefore merit consideration as valuable alternatives to traditional multivariate regression techniques in epidemiologic studies.     

Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa

Background:

The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known.

Methods:

From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors.

Results:

Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk.

Conclusion:

Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa.     

Specific haplotypes of the RET proto-oncogene are over-represented in patients with sporadic papillary thyroid carcinoma

Background: Papillary thyroid carcinoma (PTC), which may be sporadic (95%) or familial (5%), has a prevalence adjusted for age in the general population of 1:100 000. Somatic rearrangements of the RET proto-oncogene are present in up to 66% of sporadic tumours, while they are rarely found in familial cases.

Purpose: In order to determine if some variants of this gene, or a combination of them, might predispose to PTC, we looked for an association of RET haplotype(s) in PTC cases and in controls from four countries matched for sex, age, and population.

Methods: Four single nucleotide polymorphisms (SNPs) across the RET coding sequence were typed and haplotype frequencies were estimated. Genotype and haplotype distributions were compared among these cases and controls.

Results: Ten haplotypes were observed, the seven most frequent of which have been previously described in sporadic Hirschsprung patients and controls. The single locus analyses suggested association of exon 2 and exon 13 SNPs with sporadic PTC. The haplotype analysis showed over-representation of one haplotype in French and Italian sporadic PTC, whereas a different haplotype was significantly under-represented in French familial PTC.

Conclusions: Our data suggest that some variants of RET and some specific haplotypes may act as low penetrance alleles in the predisposition to PTC.

     

XRCC1 and hOGG1 genes and risk of nasopharyngeal carcinoma in North African countries

Although genetic susceptibility to nasopharyngeal carcinoma (NPC) has been recognized for a long time, little is known about the responsible genes. X-Ray repair cross-complementing protein 1 (XRCC1) and human 8-oxo-guanine glycosylase 1 (hOGG1) genes are involved in deoxyribonucleic acid (DNA) repair and were found associated with NPC risk in three Asian case-control studies. The objective of the present study was to test these genes in a sample from North Africa, one of the major NPC endemic regions in the world. Three single nucleotide polymorphisms (SNPs) in the XRCC1 gene and one SNP in the hOGG1 gene were genotyped in 598 NPC cases from Morocco, Algeria, and Tunisia and 545 controls frequency matched by recruitment center, age, sex, and urban/rural household. The genotype and allelic distributions for the hOGG1 (326)Ser/Cys SNP and for the XRCC1 (399)Arg/Trp, (280)Arg/His, and (194)Arg/Trp SNPs did not differ significantly among NPC cases and controls. The XRCC1 (194)Trp allele frequency was significantly lower in the North African population than in Asian population (f = 0.04 vs. 0.31 in Cantonese Chinese and 0.21 Han Chinese). The hOGG1 (326)Ser allele frequency was significantly higher in the North African population (f = 0.73) than in Asian populations (f = 0.39 in Taiwanese). The results of the present study obtained from a large sample indicate that the XRCC1 and hOGG1 genes are unlikely to play a role in the susceptibility to NPC in North Africans. Our results do not corroborate those found in Asian population on smaller samples.     

The cost of routine Aedes aegypti control and of insecticide-treated curtain implementation

Insecticide-treated curtains (ITCs) are promoted for controlling the Dengue vector Aedes aegypti. We assessed the cost of the routine Aedes control program (RACP) and the cost of ITC implementation through the RACP and health committees in Venezuela and through health volunteers in Thailand. The yearly cost of the RACP per household amounted to US$2.14 and $1.89, respectively. The ITC implementation cost over three times more, depending on the channel used. In Venezuela the RACP was the most efficient implementation-channel. It spent US$1.90 (95% confidence interval [CI]: 1.83; 1.97) per curtain distributed, of which 76.9% for the curtain itself. Implementation by health committees cost significantly (P = 0.02) more: US$2.32 (95% CI: 1.93; 2.61) of which 63% for the curtain. For ITC implementation to be at least as cost-effective as the RACP, at equal effectiveness and actual ITC prices, the attained curtain coverage and the adulticiding effect should last for 3 years.