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Kinds of Hygiene Terms modified by Hygiene Selected AbstractsThe development of an ePortfolio for life-long reflective learning and auditable professional certificationEUROPEAN JOURNAL OF DENTAL EDUCATION, Issue 3 2009R. L. Kardos Abstract Recent legislative changes, that affect all healthcare practitioners in New Zealand, have resulted in mandatory audits of practitioners who are now required to provide evidence of competence and continued professional development in the form of a professional portfolio. These changes were the motivation for our development of an electronic portfolio (ePortfolio) suitable for both undergraduate and life-long learning. Bachelor of Oral Health (BOH) students, studying to qualify as Dental Hygienists and Dental Therapists, and BOH teaching staff (who held registrations in Dental Hygiene, Dental Therapy and Dentistry) trialled the use of a personal ePortfolio for advancing their academic and professional development. The ePortfolio enables BOH students to collect evidence of their achievements and personal reflections throughout their 3 years of undergraduate study, culminating in registration and the award of an Annual Practising Certificate (APC). The ePortfolio was designed to allow users to store information and then select appropriate material to be displayed or published, thus assisting health practitioners to present high-quality evidence of their participation and achievements, and to meet the professional requirements for their APC. [source] "The New Generation": Mental Hygiene and the Portrayals of Children by the National Film Board of Canada, 1946,1967HISTORY OF EDUCATION QUARTERLY, Issue 4 2003Brian J. Low That is the achievement of the psychologists. In our own society they are very kind, and do everything for our own good. The tales of what they do elsewhere are rather terrifying. ,Hilda Neatby So Little for the Mind (1953) [source] Oral squamous cell carcinoma and cultural oral risk habits in VietnamINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 3 2010SL Priebe To cite this article: Int J Dent Hygiene,8, 2010; 159,168 DOI: 10.1111/j.1601-5037.2010.00461.x Priebe SL, Aleksej,nien, J, Zed C, Dharamsi S, Thinh DHQ, Hong NT, Cuc TTK, Thao NTP. Oral squamous cell carcinoma and cultural oral risk habits in Vietnam. Abstract: Objectives:, In South-Central Asia, 80% of head and neck cancers are found in the oral cavity and oropharynx. In Vietnam, oral cancer is often not being detected until people experience debilitating circumstances to normal oral function. The aims of the study were to explore the patterns of oral squamous cell carcinoma (OSCC) and its risk indicators, the structure of oral health care in Vietnam and trends in prevalence of cultural risk habits in southern Vietnamese patients. Materials and Methods:, A retrospective clinical study was performed from 1 July 2005 to 1 April 2006 at Ho Chi Minh City Oncology hospital in Vietnam. Of the 161 cases, 147 subjects were diagnosed with OSCC, including 100 male and 47 female adults aged 24,85 years. Data were collected by a structured interview and clinical examination. Results:, Over 40% of the women with OSCC reported chewing betel quid and the most prevalent risk habit in males was smoking (91.0%). Daily alcohol use was reported by 79.0% of males and 2.1% of females. Two-thirds of the cases of OSCC were diagnosed at the 2nd and 3rd stage of cancer. The more advanced stages of cancer were observed in males than in females. The prevalence of tobacco and alcohol use in males with OSCC was higher in this study than in the previous Vietnamese studies. Conclusion:, High frequency of risk habits in both genders was reported in OSCC Vietnamese patients. A trend of increased tobacco and alcohol use was observed in male OSCC patients. A lower prevalence of later staging in Vietnam was observed in this study than in earlier studies. [source] Dental hygienists' work environment: motivating, facilitating, but also tryingINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 3 2010A Candell To cite this article: Int J Dent Hygiene,8, 2010; 204,212 DOI: 10.1111/j.1601-5037.2009.00420.x Candell A, Engström M. Dental hygienists' work environment: motivating, facilitating, but also trying Abstract:, The aim of the present study was to describe dental hygienists' experiences of their physical and psychosocial work environment. The study was descriptive in design and used a qualitative approach. Eleven dental hygienists participated in the study and data were collected during spring 2008 using semi-structured interviews. The material was analysed using qualitative content analysis. The results showed that the dental hygienists experienced their work environment as motivating and facilitating, but at the same time as trying. The three categories revealed a theme: Being controlled in a modern environment characterized by good relationships. Motivating factors were the good relationship with co-workers, managers and patients, seeing the results of your work, having your own responsibility and making your own decisions. The new, pleasant and modern clinics, good cooperation between co-workers and varying duties were described as facilitating factors. The trying factors, as described by the dental hygienists, were above all being controlled by time limits or by some elements of the work, such as teamwork. The dental hygienists also felt stress because appointments were too-short. To conclude, the participants described their work environment as trying in several ways, despite the modern clinics and good relationships. [source] Dental hygienists' views on communicative factors and interpersonal processes in prevention and treatment of periodontal diseaseINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 3 2010J Stenman To cite this article: Int J Dent Hygiene,8, 2010; 213,218 DOI: 10.1111/j.1601-5037.2010.00459.x Stenman J, Wennström JL, Abrahamsson KH. Dental hygienists' views on communicative factors and interpersonal processes in prevention and treatment of periodontal disease. Abstract:, Objective:, The aim of this study was to explore views of DHs on communicative issues and interpersonal processes of importance in the prevention and treatment of periodontal disease. Method:, The qualitative method of Grounded Theory (GT) was chosen for data sampling and analysis. Audio-taped and open-ended interviews were conducted with 17 dental hygienists. The interviews were transcribed verbatim and analysed in a hierarchical coding process, according to the principles of GT. Result:, In the analysis a core category was identified as ,to be successful in information and oral health education and managing desirable behavioural changes'. The core concept was related to four additional categories and dimensions; (i) ,to establish a trustful relationship with the patient', (ii) ,to present information about the oral health status and to give oral hygiene instructions', (iii) ,to be professional in the role as a dental hygienist' and (iv) ,to have a supportive working environment in order to feel satisfaction with the work and to reach desirable treatment results'. Conclusion:, The results describe a psychosocial process that elucidates the importance of building a trustful relationship with the patient, feeling secure in one's professional role as a DH and last but not least, the importance of having support from colleagues and the clinical manager to be successful in the prevention and treatment of periodontal diseases. [source] Dental hygiene regulation: a global perspectiveINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 3 2008PM Johnson Abstract:, Occupational regulation of health personnel is important to professional associations and their members, the public that relies on their services and the regulatory agencies responsible for their conduct. There is increasing interest in ensuring that dental hygiene regulation fosters the continuing evolution of the profession and its contribution to oral health. The keynote address for the 2007 Regulatory Forum on Dental Hygiene, this paper discusses the rationale for and issues pertaining to occupational regulation, outlines the evolvement of dental hygiene and identifies regulatory options for the profession. Professional regulation exists to ensure public safety, health and welfare. However, negative political-economic side effects coupled with environmental pressures have resulted in increased scrutiny for health professionals. One such profession is dental hygiene. Its evolution has been dramatic, in particular over the past few decades, as illustrated by its rapidly increasing numbers and broader distribution globally, gradual shift to the baccalaureate as the entry-level educational requirement and increase in postgraduate programs and expanding scope of practice and increased professional autonomy. Regulatory changes have been more gradual. Regulation is mandatory for the vast majority of dental hygienists. Of the options available, the practice act , the most rigorous type, is predominant. Globally, regulation tends to be administered directly by the government (n = 9 countries) more so than indirectly through a dental board (n = 4) or self-regulation (n = 3). Whether regulated directly or indirectly, dental hygienists increasingly are seeking a greater role in shaping their professional future. Self-regulation, its responsibilities, misperceptions and challenges, is examined as an option. [source] Towards international curriculum standardsINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 1 2003Phebe Blitz Abstract:, In 1998, the House of Delegates of the International Federation of Dental Hygiene requested that the education committee of the federation develop curriculum guidelines to serve as models for countries that were initiating dental hygiene educational programmes. This article reviews the process of guideline development, identifies challenges and directions for the future. A review of topics, goal and descriptions of 2, 3 and 4 years is presented. The process of development of the guidelines provided an opportunity for discussion of differences in dental hygiene paradigm from various countries. Participants began to understand the legal, cultural and educational differences that have an impact on curriculum for health care. It is a beginning in the process of developing international educational standards in dental hygiene education. [source] An update of EU legislation (Directives and Regulations) on food-related issues (Safety, Hygiene, Packaging, Technology, GMOs, Additives, Radiation, Labelling): presentation and commentsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 10 2005Ioannis S. Arvanitoyannis Summary This review aims at providing an update of the current European Union (EU) Regulations and Directives on food-related issues. Initially, a brief presentation of EU legislation in terms of structure (horizontal, vertical) was attempted. EU Regulations and Directives were classified into the following categories: food safety (Hazard Analysis Critical Control Points, pesticides, radioactive, hormones, contaminants, freezing , ionisation, food additives, flavourings, packaging), genetically modified organisms, food quality, labelling, food products of plant or animal origin, imports from third countries. Apart from a synoptical presentation of all laws related to the above-mentioned topics, proper tables were compiled where the main points of each law are cited in conjunction with its effect on previous laws (repeal, modification, amendments, replacement). In such a way the reader can rapidly acquire a first approach to the topic of his interest. [source] Evaluation of NOC Measures in Home Care Nursing PracticeINTERNATIONAL JOURNAL OF NURSING TERMINOLOGIES AND CLASSIFICATION, Issue 2003Gail M. Keenan PURPOSE To evaluate the reliability, validity, usefulness, and sensitivity of 89 NOC outcomes in two Visiting Nurse Associations in Michigan. METHODS Of a total 190 NOC outcomes 89 were assigned for testing. Interrater reliability and criterion validity were assessed a total of 50 times per outcome (on 50 different patients) across the study units. The total number of times the reliability and validity were assessed for each of the 89 measures studied ranged from 5,45. Three RN research assistants (RNRAs) oversaw and participated in data collection with the help of 15 clinicians. Convenience sampling was used to identify subjects. A roster of outcomes to be studied was maintained and matched with patient conditions whenever possible until the quota of outcomes assigned had been evaluated. Clinicians and RNRAs independently rated the outcomes and indicators applicable to the patient. NANDA diagnoses, NIC interventions, and medical diagnoses were recorded. FINDINGS A total of 258 patients (mean age 62) enrolled; 60% were women, 23% were from minority groups, and 78% had no college degree. Thirty-six of the 89 NOC measures were designated "clinically useful." The 10 outcomes with the highest interrater reliability were Caregiver Home Care Readiness; Caregiver Stressors; Caregiving Endurance Potential; Infection Status; Mobility Level; Safety Status: Physical Injury; Self-Care: Activities of Daily Living; Self-Care: Bathing; Self-Care: Hygiene; and Wound Healing: Secondary Intention. Criterion measurement and repeated ratings provided evidence to support the validity and sensitivity of the NOC outcomes. Evidence also suggested that NOC label level ratings could be a feasible, reliable, and valid method of evaluating nursing outcomes under actual use. For some measures, adjustments in the scales and anchors are needed to enhance reliability. For others, it may be unrealistic to reliably score in one encounter, thus scoring should be deferred until the clinician has adequate knowledge of the patient. CONCLUSIONS Continued study and refinement that are coordinated and integrated systematically strongly recommended. Comprehensive study in an automated system with a controlled format will increase the efficiency of future studies. [source] Efficacy of plaque removal and learning effect of a powered and a manual toothbrushJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003D. Lazarescu Abstract Background: Subjects with high plaque and gingivitis scores can profit most from the introduction of new manual or powered tooth brushes. To improve their hygiene, not only the technical characteristics of new brushes but also the learning effect in efficient handling are of importance. Aim: The present study compared the efficacy in plaque removal of an electric and a manual toothbrush in a general population and analysed the learning effect in efficient handling. Method: Eighty healthy subjects, unfamiliar with electric brushes, were divided into two groups: group 1 used the Philips/Jordan HP 735 powered brush and group 2 used a manual brush, Oral-B40+. Plaque index (PI) and gingival bleeding index (GBI) were assessed at baseline and at weeks 3, 6, 12 and 18. After each evaluation, patients abstained from oral hygiene for 24 h. The next day a 3-min supervised brushing was perfomed. Before and after this brushing, PI was assessed for the estimation of the individual learning effect. The study was single blinded. Results: Over the 18-week period, PI reduced gradually and statistically significantly (p<0.001) in group 1 from 2.9 (±0.38) to 1.5 (±0.24) and in group 2 from 2.9 (±0.34) to 2.2 (±0.23). From week 3 onwards, the difference between groups was statistically significant (p<0.001). The bleeding index decreased in group 1 from 28% (±17%) to 7% (±5%) (p<0.001) and in group 2 from 30% (±12%) to 12% (±6%) (p<0.001). The difference between groups was statistically significant (p<0.001) from week 6 onwards. The learning effect, expressed as the percentage of plaque reduction after 3 min of supervised brushing, was 33% for group 1 and 26% for group 2 at week 0. This percentage increased at week 18 to 64% in group 1 and 44% in group 2 (difference between groups statistically significant: p<0.001). Conclusion: The powered brush was significantly more efficient in removing plaque and improving gingival health than the manual brush in the group of subjects unfamiliar with electric brushes. There was also a significant learning effect that was more pronounced with the electric toothbrush. Zusammenfassung Hintergrund: Personen mit einem hohen Plaque- und Gingivitisindex können am meisten von der Einführung einer neuen Hand- oder elektrischen Zahnbürste profitieren. Um ihre Hygiene zu verbessern, sind nicht nur die technischen Charakteristika der neuen Bürste von Wichtigkeit, sondern auch der Lerneffekt für das effiziente Nutzen. Ziel: Die vorliegende Studie vergleicht die Effektivität bei der Plaqueentfernung bei einer elektrischen und einer Handzahnbürste in einer allgemeinen Bevölkerung und analysiert den Lerneffekt bei der effektiven Benutzung. Methoden: 80 gesunde Personen, die nicht an elektrische Zahnbürsten gewöhnt waren, wurden in zwei Gruppen eingeteilt: Gruppe 1 nutzte die Philips/Jordan HP 735 elektrische Bürste und die Gruppe 2 eine Handbürste, Oral-B40+. Der Plaqueindex (PI) und der gingivale Blutungsindex (GBI) wurden zur Basis und zu den Wochen 3, 6, 12 und 18 gemessen. Nach jeder Evaluation enthielten sich die Patienten für 24 Stunden der oralen Hygiene. Am nächsten Tag wurde ein beaufsichtigtes Bürsten durchgeführt. Vor und nach diesem Bürsten wurde der Plaqueindex für die Einschätzung des individuellen Lerneffektes aufgezeichnet. Die Studie war einfach blind. Ergebnisse: Über die 18wöchige Periode reduzierte sich der PI graduell und statistisch signifikant (p<0,001) in der Gruppe 1 von 2.9 (±0.38) auf 1.5 (±0.24) und in der Gruppe 2 von 2.9 (±0.34) auf 2.2 (± 0.23). Von der Woche 3 aufwärts wurde die Differenz zwischen den beiden Gruppen signifikant (p<0.001). Der Blutungsindex verringerte sich in der Gruppe 1 von 28% (± 17%) auf 7% (±5%) (p<0.001) und in der Gruppe 2 von 30% (±12%) auf 12% (±6%) (p<0.001). Die Differenz zwischen den beiden Gruppen war statistisch signifikant (p<0.001) von der 6. Woche an. Der Lerneffekt, ausgedrückt durch den Prozentsatz der Plaquereduktion nach 3 Minuten beaufsichtigtem Putzen, war 33% bei der Gruppe 1 und 26% bei der Gruppe 2 zur Woche 0. Dieser Prozentsatz vergrößerte sich zur Woche 18 auf 64% in der Gruppe 1 und auf 44% in der Gruppe 2 (Differenzen zwischen den Gruppen statistisch signifikant: p<0.001). Schlussfolgerung: Die elektrische Zahnbürste war signifikant mehr effektiv in der Plaqueentfernung und Verbesserung der gingivalen Gesundheit als die Handbürste in dieser Gruppe von Personen, die nicht an elektrische Bürsten gewöhnt waren. Es gab auch einen signifikanten Lerneffekt, welcher bei der Nutzung der elektrischen Zahnbürste größer war. Résumé Contexte: Des sujets présentant des scores de plaque et de gingivite élevés peuvent bénéficier de façon importante de l'apparition de nouvelles brosses manuelles et électriques. Pour améliorer leur hygiène, les caractéristiques techniques, mais aussi les instructions pour une manipulation efficace sont des éléments importants. But: Cette étude compare l'efficacité d'élimination de la plaque d'une brosse à dent manuelle et électrique dans une population générale et analyse l'effet de l'apprentissage pour une manipulation efficace. Méthode: 80 sujets sains, pas habitués aux brosses électrique, ont été divisés en deux groupes : Le groupe 1 utilisa la brosse Philips/Jordan HP 735 électrique et le groupe 2, une brosse manuelle Oral-B40+. L'indice de plaque (PI) et l'indice de saignement gingival (GBI) furent enregistrés initialement et à 3, 6, 12 et 18 semaines. Après chaque évaluation, les patients arrêtaient l'hygiène buccale pendant 24 heures. Le jour suivant, un brossage surveillé de 3 minutes était réalisé. Avant et après ce brossage, l'indice de plaque était relevé en vue de l'estimation de l'effet de l'apprentissage. L'étude était en aveugle simple. Résultats: Pendant la période de 18 semaines, le PI diminuait graduellement et de façon statistiquement significative (p<0.001) dans le groupe 1, de 2.9 (±0.38) à 1.5 (±0.24) et dans le groupe 2 de 2.9 (±0.34) à 2.2 (±0.23). A partir de la troisième semaine, la différence était déjà significative (p<0.001). L'indice de saignement diminuait dans le groupe 1 de 28% (±17%) à 7% (±5%) (p<0.001) et dans le groupe 2, de 30% (±12%) à 12% (±6%) (p<0.001). La différence entre les groupes était statistiquement significative à partir de la sixième semaine. L'effet de l'apprentissage, exprimé en pourcentage de la réduction de plaque après un brossage de 3 minutes surveillé fut de 33% pour le groupe 1 et de 26 % pour le groupe 2 initialement et augmentait lors de la semaine 18 jusqu'à 64% dans le groupe 1 et 44% dans le groupe 2 (différence entre les groupes significative: p<0.001). [source] Effects of academic stress on oral hygiene , a potential link between stress and plaque-associated disease?JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2001Renate Deinzer Abstract Background: While there seems to be a common belief that psychosocial stress affects oral hygiene behavior, this assumption has rarely been proved. The present study thus aims to analyse stress effects on oral hygiene. Material and Methods: 16 matched pairs of medical students each consisting of 1 student participating in a major academic exam and 1 control without current academic stress, were formed on the basis of baseline plaque levels. At baseline, a professional tooth cleaning was performed. On the last day of exams, students answered questionnaires about oral hygiene during the exams and were afterwards asked to attend for a 2nd dental examination, of which they had no prior knowledge. Results: On the last day of exams, approximately 6 weeks after professional tooth cleaning, 20.9±18.3% of control students' sites but only 10.5±9.3% of exam students' sites were found to be free of any plaque (p=0.022). Differences were most obvious at oral, as compared to vestibular, sites. Exam students reported a reduction in thoroughness (p=0.019) but not of frequency of oral hygiene behavior. Conclusion: The study strongly supports the assumption that psychosocial stress may induce neglect of oral hygiene and increase of plaque accumulation. Zusammenfassung Hintergrund: Obwohl es eine allgemeine Annahme zu sein scheint, daß psycho-sozialer Stress die Mundhygiene beeinflußt, ist diese Annahme bisher selten geprüft worden. Mit der gegenwärtigen Studie sollen deshalb Stresseffekte auf die Mundhygiene analysiert werden. Material und Methoden. 16 gematchte Paare von Medizinstudenten, von denen jedes aus einem Student, der an einem wichtigen akademischen Examen teilnahm, und einer Kontrolle ohne gegenwärtigen akademischen Stress bestand, wurden auf der Basis von Baseline Plaquewerten gebildet. Zur Baseline wurde eine professionelle Zahnreinigung durchgeführt. Zum letzten Tag der Examen beantworteten die Studenten Fragebögen über die Mundhygiene während des Examens und wurde danach zu einer zweiten zahnärztlichen Überprüfung aufgefordert, von der sie zuvor keine Kenntnis hatten. Ergebnisse: Am letzten Tag des Examens ungefähr 6 Wochen nach der professionellen Zahnreinigung waren 20.9%±18.3% der Flächen der Kontrollstudenten, aber nur 10.5%±9.3% der Flächen der Examensstudenten plaquefrei (p=0.022). Die Differenzen waren an den oralen Flächen am deutlichsten, verglichen mit den vestibulären Flächen. Die Examensstudenten berichteten über eine Reduktion in der Gründlichkeit (p=0.019), aber nicht in der Häufigkeit der oralen Hygiene. Schlußfolgerung: Die Studie unterstützt nachhaltig die Annahme, daß psycho-sozialer Stress eine Vernachlässigung der oralen Hygiene und eine Zunahme der Plaqueakkumulation induziert. Résumé Bien que l'idée qu'un psycho-asocial puisse affecter les habitudes d'hygiène buccale, celle-ci n'a que rarement été prouvée. L'étude présente a donc analysé les effets du stress sur l'hygiène buccale. 16 paires d'étudiants en médicine dont l'un des deux participait à un examen académique majeur ont été formés sur base du niveau de plaque dentaire lors de l'examen initial. Lors de cet examen, un nettoyage professionnel a été effectué. Le dernier jour des examens les étudaints répondaient à des questionnaires à propos de leur hygiène buccale durant les examens et ont ensuite été réexaminés, ce dont ils n'avaint pas été informés précédement. Le dernier jour des examens, environ 6 semaines après le nettoyage professionnel, 21±18% des sites contrôles mais aussi 11±9% des sites des étudiants en examen n'avaient pas de trace de plaque dentaire (p=0.022). Les différenes les plus visibles se situaient au niveau lingual comparé aux sites vestibulaires. Chaque étudiant avait une réduction dans la qualité (p=0.019) mais non dans la fréquence de l'habitude d'hygiène buccale. Cette étude soutient grandement l'idée que le stress psychosocial engendre une négligence de l'hygiène buccale et augmente ainsi l'accumulation de plaque dentaire. [source] Bilingual Humor, Verbal Hygiene, and the Gendered Contradictions of Cultural Citizenship in Early Mexican American ComedyJOURNAL OF LINGUISTIC ANTHROPOLOGY, Issue 2 2003Peter C. Haney This article examines the paradoxes of linguistic purism in a series of sound recordings of comic dialogues made by Mexican immigrant comedians in San Antonio, Texas, during the Depression. The dialogues present characters who mix English and Spanish as transgressors of gender roles and national identities, reserving their harshest criticism for women. However, bilingual wordplay in the dialogues suggests a dialectically opposed ideological move toward a celebration of linguistic and cultural hybridity. [source] Using School Staff to Establish a Preventive Network of Care to Improve Elementary School Students' Control of AsthmaJOURNAL OF SCHOOL HEALTH, Issue 6 2006Jean-Marie Bruzzese To address these problems, Columbia University and the New York City Department of Education and the New York City Department of Health and Mental Hygiene undertook a randomized controlled trial to test the efficacy of a comprehensive school-based asthma program. In this intervention, school nurses were trained to facilitate the establishment of a preventive network of care for children with asthma by coordinating communications and fostering relationships between families, PCPs, and school personnel. PCPs also received training regarding asthma management. There was limited support for this model. While case detection helped nurses identify additional students with asthma and nurses increased the amount of time spent on asthma-related tasks, PCPs did not change their medical management of asthma. Few improvements in health outcomes were achieved. Relative to controls, 12-months posttest intervention students had a reduction in activity limitations due to asthma (,35% vs ,9%, p < .05) and days with symptoms (26% vs 39%, p = .06). The intervention had no impact on the use of urgent health care services, school attendance, or caregiver's quality of life. There were also no improvements at 24-months postintervention. We faced many challenges related to case detection, training, and implementing preventive care activities, which may have hindered our success. We present these challenges, describe how we coped with them, and discuss the lessons we learned. (J Sch Health. 2006;76(6):307-312) [source] A Military Challenge to Managing Feminine and Personal HygieneJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 4 2001Diane Wind Wardell PhD PURPOSE To examine the personal remembrances of a group of military women concerning their experiences with hygiene issues during service in a hostile environment. DATA SOURCES Verbatim transcripts of focused interviews from 33 women who had been deployed to combat or the field were subjected to content analysis. Questions related to the womens' experiences in cleansing the body, collecting menses waste, and protecting against genitourinary infection in a hostile environment. CONCLUSIONS Management of personal hygiene needs was often difficult and consumed a great deal of time. Hygiene issues affected women's attitudes, practice, work, morale and coping. IMPLICATIONS FOR PRACTICE By understanding the hygiene needs and practices of military woman changes can be made that have the potential to affect health promotion and disease prevention strategies for all women. [source] Mental Hygiene and Socio-Environmental FactorsTHE MILBANK QUARTERLY, Issue 4 2005R.H. FELIX MD First page of article [source] European Mathematical Genetics Meeting, Heidelberg, Germany, 12th,13th April 2007ANNALS OF HUMAN GENETICS, Issue 4 2007Article first published online: 28 MAY 200 Saurabh Ghosh 11 Indian Statistical Institute, Kolkata, India High correlations between two quantitative traits may be either due to common genetic factors or common environmental factors or a combination of both. In this study, we develop statistical methods to extract the contribution of a common QTL to the total correlation between the components of a bivariate phenotype. Using data on bivariate phenotypes and marker genotypes for sib-pairs, we propose a test for linkage between a common QTL and a marker locus based on the conditional cross-sib trait correlations (trait 1 of sib 1 , trait 2 of sib 2 and conversely) given the identity-by-descent sharing at the marker locus. The null hypothesis cannot be rejected unless there exists a common QTL. We use Monte-Carlo simulations to evaluate the performance of the proposed test under different trait parameters and quantitative trait distributions. An application of the method is illustrated using data on two alcohol-related phenotypes from the Collaborative Study On The Genetics Of Alcoholism project. Rémi Kazma 1 , Catherine Bonaïti-Pellié 1 , Emmanuelle Génin 12 INSERM UMR-S535 and Université Paris Sud, Villejuif, 94817, France Keywords: Gene-environment interaction, sibling recurrence risk, exposure correlation Gene-environment interactions may play important roles in complex disease susceptibility but their detection is often difficult. Here we show how gene-environment interactions can be detected by investigating the degree of familial aggregation according to the exposure of the probands. In case of gene-environment interaction, the distribution of genotypes of affected individuals, and consequently the risk in relatives, depends on their exposure. We developed a test comparing the risks in sibs according to the proband exposure. To evaluate the properties of this new test, we derived the formulas for calculating the expected risks in sibs according to the exposure of probands for various values of exposure frequency, relative risk due to exposure alone, frequencies of latent susceptibility genotypes, genetic relative risks and interaction coefficients. We find that the ratio of risks when the proband is exposed and not exposed is a good indicator of the interaction effect. We evaluate the power of the test for various sample sizes of affected individuals. We conclude that this test is valuable for diseases with moderate familial aggregation, only when the role of the exposure has been clearly evidenced. Since a correlation for exposure among sibs might lead to a difference in risks among sibs in the different proband exposure strata, we also add an exposure correlation coefficient in the model. Interestingly, we find that when this correlation is correctly accounted for, the power of the test is not decreased and might even be significantly increased. Andrea Callegaro 1 , Hans J.C. Van Houwelingen 1 , Jeanine Houwing-Duistermaat 13 Dept. of Medical Statistics and Bioinformatics, Leiden University Medical Center, The Netherlands Keywords: Survival analysis, age at onset, score test, linkage analysis Non parametric linkage (NPL) analysis compares the identical by descent (IBD) sharing in sibling pairs to the expected IBD sharing under the hypothesis of no linkage. Often information is available on the marginal cumulative hazards (for example breast cancer incidence curves). Our aim is to extend the NPL methods by taking into account the age at onset of selected sibling pairs using these known marginal hazards. Li and Zhong (2002) proposed a (retrospective) likelihood ratio test based on an additive frailty model for genetic linkage analysis. From their model we derive a score statistic for selected samples which turns out to be a weighed NPL method. The weights depend on the marginal cumulative hazards and on the frailty parameter. A second approach is based on a simple gamma shared frailty model. Here, we simply test whether the score function of the frailty parameter depends on the excess IBD. We compare the performance of these methods using simulated data. Céline Bellenguez 1 , Carole Ober 2 , Catherine Bourgain 14 INSERM U535 and University Paris Sud, Villejuif, France 5 Department of Human Genetics, The University of Chicago, USA Keywords: Linkage analysis, linkage disequilibrium, high density SNP data Compared with microsatellite markers, high density SNP maps should be more informative for linkage analyses. However, because they are much closer, SNPs present important linkage disequilibrium (LD), which biases classical nonparametric multipoint analyses. This problem is even stronger in population isolates where LD extends over larger regions with a more stochastic pattern. We investigate the issue of linkage analysis with a 500K SNP map in a large and inbred 1840-member Hutterite pedigree, phenotyped for asthma. Using an efficient pedigree breaking strategy, we first identified linked regions with a 5cM microsatellite map, on which we focused to evaluate the SNP map. The only method that models LD in the NPL analysis is limited in both the pedigree size and the number of markers (Abecasis and Wigginton, 2005) and therefore could not be used. Instead, we studied methods that identify sets of SNPs with maximum linkage information content in our pedigree and no LD-driven bias. Both algorithms that directly remove pairs of SNPs in high LD and clustering methods were evaluated. Null simulations were performed to control that Zlr calculated with the SNP sets were not falsely inflated. Preliminary results suggest that although LD is strong in such populations, linkage information content slightly better than that of microsatellite maps can be extracted from dense SNP maps, provided that a careful marker selection is conducted. In particular, we show that the specific LD pattern requires considering LD between a wide range of marker pairs rather than only in predefined blocks. Peter Van Loo 1,2,3 , Stein Aerts 1,2 , Diether Lambrechts 4,5 , Bernard Thienpont 2 , Sunit Maity 4,5 , Bert Coessens 3 , Frederik De Smet 4,5 , Leon-Charles Tranchevent 3 , Bart De Moor 2 , Koen Devriendt 3 , Peter Marynen 1,2 , Bassem Hassan 1,2 , Peter Carmeliet 4,5 , Yves Moreau 36 Department of Molecular and Developmental Genetics, VIB, Belgium 7 Department of Human Genetics, University of Leuven, Belgium 8 Bioinformatics group, Department of Electrical Engineering, University of Leuven, Belgium 9 Department of Transgene Technology and Gene Therapy, VIB, Belgium 10 Center for Transgene Technology and Gene Therapy, University of Leuven, Belgium Keywords: Bioinformatics, gene prioritization, data fusion The identification of genes involved in health and disease remains a formidable challenge. Here, we describe a novel bioinformatics method to prioritize candidate genes underlying pathways or diseases, based on their similarity to genes known to be involved in these processes. It is freely accessible as an interactive software tool, ENDEAVOUR, at http://www.esat.kuleuven.be/endeavour. Unlike previous methods, ENDEAVOUR generates distinct prioritizations from multiple heterogeneous data sources, which are then integrated, or fused, into one global ranking using order statistics. ENDEAVOUR prioritizes candidate genes in a three-step process. First, information about a disease or pathway is gathered from a set of known "training" genes by consulting multiple data sources. Next, the candidate genes are ranked based on similarity with the training properties obtained in the first step, resulting in one prioritized list for each data source. Finally, ENDEAVOUR fuses each of these rankings into a single global ranking, providing an overall prioritization of the candidate genes. Validation of ENDEAVOUR revealed it was able to efficiently prioritize 627 genes in disease data sets and 76 genes in biological pathway sets, identify candidates of 16 mono- or polygenic diseases, and discover regulatory genes of myeloid differentiation. Furthermore, the approach identified YPEL1 as a novel gene involved in craniofacial development from a 2-Mb chromosomal region, deleted in some patients with DiGeorge-like birth defects. Finally, we are currently evaluating a pipeline combining array-CGH, ENDEAVOUR and in vivo validation in zebrafish to identify novel genes involved in congenital heart defects. Mark Broom 1 , Graeme Ruxton 2 , Rebecca Kilner 311 Mathematics Dept., University of Sussex, UK 12 Division of Environmental and Evolutionary Biology, University of Glasgow, UK 13 Department of Zoology, University of Cambridge, UK Keywords: Evolutionarily stable strategy, parasitism, asymmetric game Brood parasites chicks vary in the harm that they do to their companions in the nest. In this presentation we use game-theoretic methods to model this variation. Our model considers hosts which potentially abandon single nestlings and instead choose to re-allocate their reproductive effort to future breeding, irrespective of whether the abandoned chick is the host's young or a brood parasite's. The parasite chick must decide whether or not to kill host young by balancing the benefits from reduced competition in the nest against the risk of desertion by host parents. The model predicts that three different types of evolutionarily stable strategies can exist. (1) Hosts routinely rear depleted broods, the brood parasite always kills host young and the host never then abandons the nest. (2) When adult survival after deserting single offspring is very high, hosts always abandon broods of a single nestling and the parasite never kills host offspring, effectively holding them as hostages to prevent nest desertion. (3) Intermediate strategies, in which parasites sometimes kill their nest-mates and host parents sometimes desert nests that contain only a single chick, can also be evolutionarily stable. We provide quantitative descriptions of how the values given to ecological and behavioral parameters of the host-parasite system influence the likelihood of each strategy and compare our results with real host-brood parasite associations in nature. Martin Harrison 114 Mathematics Dept, University of Sussex, UK Keywords: Brood parasitism, games, host, parasite The interaction between hosts and parasites in bird populations has been studied extensively. Game theoretical methods have been used to model this interaction previously, but this has not been studied extensively taking into account the sequential nature of this game. We consider a model allowing the host and parasite to make a number of decisions, which depend on a number of natural factors. The host lays an egg, a parasite bird will arrive at the nest with a certain probability and then chooses to destroy a number of the host eggs and lay one of it's own. With some destruction occurring, either natural or through the actions of the parasite, the host chooses to continue, eject an egg (hoping to eject the parasite) or abandon the nest. Once the eggs have hatched the game then falls to the parasite chick versus the host. The chick chooses to destroy or eject a number of eggs. The final decision is made by the host, choosing whether to raise or abandon the chicks that are in the nest. We consider various natural parameters and probabilities which influence these decisions. We then use this model to look at real-world situations of the interactions of the Reed Warbler and two different parasites, the Common Cuckoo and the Brown-Headed Cowbird. These two parasites have different methods in the way that they parasitize the nests of their hosts. The hosts in turn have a different reaction to these parasites. Arne Jochens 1 , Amke Caliebe 2 , Uwe Roesler 1 , Michael Krawczak 215 Mathematical Seminar, University of Kiel, Germany 16 Institute of Medical Informatics and Statistics, University of Kiel, Germany Keywords: Stepwise mutation model, microsatellite, recursion equation, temporal behaviour We consider the stepwise mutation model which occurs, e.g., in microsatellite loci. Let X(t,i) denote the allelic state of individual i at time t. We compute expectation, variance and covariance of X(t,i), i=1,,,N, and provide a recursion equation for P(X(t,i)=z). Because the variance of X(t,i) goes to infinity as t grows, for the description of the temporal behaviour, we regard the scaled process X(t,i)-X(t,1). The results furnish a better understanding of the behaviour of the stepwise mutation model and may in future be used to derive tests for neutrality under this model. Paul O'Reilly 1 , Ewan Birney 2 , David Balding 117 Statistical Genetics, Department of Epidemiology and Public Health, Imperial, College London, UK 18 European Bioinformatics Institute, EMBL, Cambridge, UK Keywords: Positive selection, Recombination rate, LD, Genome-wide, Natural Selection In recent years efforts to develop population genetics methods that estimate rates of recombination and levels of natural selection in the human genome have intensified. However, since the two processes have an intimately related impact on genetic variation their inference is vulnerable to confounding. Genomic regions subject to recent selection are likely to have a relatively recent common ancestor and consequently less opportunity for historical recombinations that are detectable in contemporary populations. Here we show that selection can reduce the population-based recombination rate estimate substantially. In genome-wide studies for detecting selection we observe a tendency to highlight loci that are subject to low levels of recombination. We find that the outlier approach commonly adopted in such studies may have low power unless variable recombination is accounted for. We introduce a new genome-wide method for detecting selection that exploits the sensitivity to recent selection of methods for estimating recombination rates, while accounting for variable recombination using pedigree data. Through simulations we demonstrate the high power of the Ped/Pop approach to discriminate between neutral and adaptive evolution, particularly in the context of choosing outliers from a genome-wide distribution. Although methods have been developed showing good power to detect selection ,in action', the corresponding window of opportunity is small. In contrast, the power of the Ped/Pop method is maintained for many generations after the fixation of an advantageous variant Sarah Griffiths 1 , Frank Dudbridge 120 MRC Biostatistics Unit, Cambridge, UK Keywords: Genetic association, multimarker tag, haplotype, likelihood analysis In association studies it is generally too expensive to genotype all variants in all subjects. We can exploit linkage disequilibrium between SNPs to select a subset that captures the variation in a training data set obtained either through direct resequencing or a public resource such as the HapMap. These ,tag SNPs' are then genotyped in the whole sample. Multimarker tagging is a more aggressive adaptation of pairwise tagging that allows for combinations of two or more tag SNPs to predict an untyped SNP. Here we describe a new method for directly testing the association of an untyped SNP using a multimarker tag. Previously, other investigators have suggested testing a specific tag haplotype, or performing a weighted analysis using weights derived from the training data. However these approaches do not properly account for the imperfect correlation between the tag haplotype and the untyped SNP. Here we describe a straightforward approach to testing untyped SNPs using a missing-data likelihood analysis, including the tag markers as nuisance parameters. The training data is stacked on top of the main body of genotype data so there is information on how the tag markers predict the genotype of the untyped SNP. The uncertainty in this prediction is automatically taken into account in the likelihood analysis. This approach yields more power and also a more accurate prediction of the odds ratio of the untyped SNP. Anke Schulz 1 , Christine Fischer 2 , Jenny Chang-Claude 1 , Lars Beckmann 121 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany 22 Institute of Human Genetics, University of Heidelberg, Germany Keywords: Haplotype, haplotype sharing, entropy, Mantel statistics, marker selection We previously introduced a new method to map genes involved in complex diseases, using haplotype sharing-based Mantel statistics to correlate genetic and phenotypic similarity. Although the Mantel statistic is powerful in narrowing down candidate regions, the precise localization of a gene is hampered in genomic regions where linkage disequilibrium is so high that neighboring markers are found to be significant at similar magnitude and we are not able to discriminate between them. Here, we present a new approach to localize susceptibility genes by combining haplotype sharing-based Mantel statistics with an iterative entropy-based marker selection algorithm. For each marker at which the Mantel statistic is evaluated, the algorithm selects a subset of surrounding markers. The subset is chosen to maximize multilocus linkage disequilibrium, which is measured by the normalized entropy difference introduced by Nothnagel et al. (2002). We evaluated the algorithm with respect to type I error and power. Its ability to localize the disease variant was compared to the localization (i) without marker selection and (ii) considering haplotype block structure. Case-control samples were simulated from a set of 18 haplotypes, consisting of 15 SNPs in two haplotype blocks. The new algorithm gave correct type I error and yielded similar power to detect the disease locus compared to the alternative approaches. The neighboring markers were clearly less often significant than the causal locus, and also less often significant compared to the alternative approaches. Thus the new algorithm improved the precision of the localization of susceptibility genes. Mark M. Iles 123 Section of Epidemiology and Biostatistics, LIMM, University of Leeds, UK Keywords: tSNP, tagging, association, HapMap Tagging SNPs (tSNPs) are commonly used to capture genetic diversity cost-effectively. However, it is important that the efficacy of tSNPs is correctly estimated, otherwise coverage may be insufficient. If the pilot sample from which tSNPs are chosen is too small or the initial marker map too sparse, tSNP efficacy may be overestimated. An existing estimation method based on bootstrapping goes some way to correct for insufficient sample size and overfitting, but does not completely solve the problem. We describe a novel method, based on exclusion of haplotypes, that improves on the bootstrap approach. Using simulated data, the extent of the sample size problem is investigated and the performance of the bootstrap and the novel method are compared. We incorporate an existing method adjusting for marker density by ,SNP-dropping'. We find that insufficient sample size can cause large overestimates in tSNP efficacy, even with as many as 100 individuals, and the problem worsens as the region studied increases in size. Both the bootstrap and novel method correct much of this overestimate, with our novel method consistently outperforming the bootstrap method. We conclude that a combination of insufficient sample size and overfitting may lead to overestimation of tSNP efficacy and underpowering of studies based on tSNPs. Our novel approach corrects for much of this bias and is superior to the previous method. Sample sizes larger than previously suggested may still be required for accurate estimation of tSNP efficacy. This has obvious ramifications for the selection of tSNPs from HapMap data. Claudio Verzilli 1 , Juliet Chapman 1 , Aroon Hingorani 2 , Juan Pablo-Casas 1 , Tina Shah 2 , Liam Smeeth 1 , John Whittaker 124 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, UK 25 Division of Medicine, University College London, UK Keywords: Meta-analysis, Genetic association studies We present a Bayesian hierarchical model for the meta-analysis of candidate gene studies with a continuous outcome. Such studies often report results from association tests for different, possibly study-specific and non-overlapping markers (typically SNPs) in the same genetic region. Meta analyses of the results at each marker in isolation are seldom appropriate as they ignore the correlation that may exist between markers due to linkage disequlibrium (LD) and cannot assess the relative importance of variants at each marker. Also such marker-wise meta analyses are restricted to only those studies that have typed the marker in question, with a potential loss of power. A better strategy is one which incorporates information about the LD between markers so that any combined estimate of the effect of each variant is corrected for the effect of other variants, as in multiple regression. Here we develop a Bayesian hierarchical linear regression that models the observed genotype group means and uses pairwise LD measurements between markers as prior information to make posterior inference on adjusted effects. The approach is applied to the meta analysis of 24 studies assessing the effect of 7 variants in the C-reactive protein (CRP) gene region on plasma CRP levels, an inflammatory biomarker shown in observational studies to be positively associated with cardiovascular disease. Cathryn M. Lewis 1 , Christopher G. Mathew 1 , Theresa M. Marteau 226 Dept. of Medical and Molecular Genetics, King's College London, UK 27 Department of Psychology, King's College London, UK Keywords: Risk, genetics, CARD15, smoking, model Recently progress has been made in identifying mutations that confer susceptibility to complex diseases, with the potential to use these mutations in determining disease risk. We developed methods to estimate disease risk based on genotype relative risks (for a gene G), exposure to an environmental factor (E), and family history (with recurrence risk ,R for a relative of type R). ,R must be partitioned into the risk due to G (which is modelled independently) and the residual risk. The risk model was then applied to Crohn's disease (CD), a severe gastrointestinal disease for which smoking increases disease risk approximately 2-fold, and mutations in CARD15 confer increased risks of 2.25 (for carriers of a single mutation) and 9.3 (for carriers of two mutations). CARD15 accounts for only a small proportion of the genetic component of CD, with a gene-specific ,S, CARD15 of 1.16, from a total sibling relative risk of ,S= 27. CD risks were estimated for high-risk individuals who are siblings of a CD case, and who also smoke. The CD risk to such individuals who carry two CARD15 mutations is approximately 0.34, and for those carrying a single CARD15 mutation the risk is 0.08, compared to a population prevalence of approximately 0.001. These results imply that complex disease genes may be valuable in estimating with greater precision than has hitherto been possible disease risks in specific, easily identified subgroups of the population with a view to prevention. Yurii Aulchenko 128 Department of Epidemiology & Biostatistics, Erasmus Medical Centre Rotterdam, The Netherlands Keywords: Compression, information, bzip2, genome-wide SNP data, statistical genetics With advances in molecular technology, studies accessing millions of genetic polymorphisms in thousands of study subjects will soon become common. Such studies generate large amounts of data, whose effective storage and management is a challenge to the modern statistical genetics. Standard file compression utilities, such as Zip, Gzip and Bzip2, may be helpful to minimise the storage requirements. Less obvious is the fact that the data compression techniques may be also used in the analysis of genetic data. It is known that the efficiency of a particular compression algorithm depends on the probability structure of the data. In this work, we compared different standard and customised tools using the data from human HapMap project. Secondly, we investigate the potential uses of data compression techniques for the analysis of linkage, association and linkage disequilibrium Suzanne Leal 1 , Bingshan Li 129 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, USA Keywords: Consanguineous pedigrees, missing genotype data Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al (2005) that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. The false-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. Which family members will aid in the reduction of false-positive evidence of linkage is highly dependent on which other family members are genotyped. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. When parental genotypes are not available, false-positive evidence for linkage can be reduced by including in the analysis genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents. Najaf Amin 1 , Yurii Aulchenko 130 Department of Epidemiology & Biostatistics, Erasmus Medical Centre Rotterdam, The Netherlands Keywords: Genomic Control, pedigree structure, quantitative traits The Genomic Control (GC) method was originally developed to control for population stratification and cryptic relatedness in association studies. This method assumes that the effect of population substructure on the test statistics is essentially constant across the genome, and therefore unassociated markers can be used to estimate the effect of confounding onto the test statistic. The properties of GC method were extensively investigated for different stratification scenarios, and compared to alternative methods, such as the transmission-disequilibrium test. The potential of this method to correct not for occasional cryptic relations, but for regular pedigree structure, however, was not investigated before. In this work we investigate the potential of the GC method for pedigree-based association analysis of quantitative traits. The power and type one error of the method was compared to standard methods, such as the measured genotype (MG) approach and quantitative trait transmission-disequilibrium test. In human pedigrees, with trait heritability varying from 30 to 80%, the power of MG and GC approach was always higher than that of TDT. GC had correct type 1 error and its power was close to that of MG under moderate heritability (30%), but decreased with higher heritability. William Astle 1 , Chris Holmes 2 , David Balding 131 Department of Epidemiology and Public Health, Imperial College London, UK 32 Department of Statistics, University of Oxford, UK Keywords: Population structure, association studies, genetic epidemiology, statistical genetics In the analysis of population association studies, Genomic Control (Devlin & Roeder, 1999) (GC) adjusts the Armitage test statistic to correct the type I error for the effects of population substructure, but its power is often sub-optimal. Turbo Genomic Control (TGC) generalises GC to incorporate co-variation of relatedness and phenotype, retaining control over type I error while improving power. TGC is similar to the method of Yu et al. (2006), but we extend it to binary (case-control) in addition to quantitative phenotypes, we implement improved estimation of relatedness coefficients, and we derive an explicit statistic that generalizes the Armitage test statistic and is fast to compute. TGC also has similarities to EIGENSTRAT (Price et al., 2006) which is a new method based on principle components analysis. The problems of population structure(Clayton et al., 2005) and cryptic relatedness (Voight & Pritchard, 2005) are essentially the same: if patterns of shared ancestry differ between cases and controls, whether distant (coancestry) or recent (cryptic relatedness), false positives can arise and power can be diminished. With large numbers of widely-spaced genetic markers, coancestry can now be measured accurately for each pair of individuals via patterns of allele-sharing. Instead of modelling subpopulations, we work instead with a coancestry coefficient for each pair of individuals in the study. We explain the relationships between TGC, GC and EIGENSTRAT. We present simulation studies and real data analyses to illustrate the power advantage of TGC in a range of scenarios incorporating both substructure and cryptic relatedness. References Clayton, D. G.et al. (2005) Population structure, differential bias and genomic control in a large-scale case-control association study. Nature Genetics37(11) November 2005. Devlin, B. & Roeder, K. (1999) Genomic control for association studies. Biometics55(4) December 1999. Price, A. L.et al. (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics38(8) (August 2006). Voight, B. J. & Pritchard, J. K. (2005) Confounding from cryptic relatedness in case-control association studies. Public Library of Science Genetics1(3) September 2005. Yu, J.et al. (2006) A unified mixed-model method for association mapping that accounts for multiple levels of relatedness. Nature Genetics38(2) February 2006. Hervé Perdry 1 , Marie-Claude Babron 1 , Françoise Clerget-Darpoux 133 INSERM U535 and Univ. Paris Sud, UMR-S 535, Villejuif, France Keywords: Modifier genes, case-parents trios, ordered transmission disequilibrium test A modifying locus is a polymorphic locus, distinct from the disease locus, which leads to differences in the disease phenotype, either by modifying the penetrance of the disease allele, or by modifying the expression of the disease. The effect of such a locus is a clinical heterogeneity that can be reflected by the values of an appropriate covariate, such as the age of onset, or the severity of the disease. We designed the Ordered Transmission Disequilibrium Test (OTDT) to test for a relation between the clinical heterogeneity, expressed by the covariate, and marker genotypes of a candidate gene. The method applies to trio families with one affected child and his parents. Each family member is genotyped at a bi-allelic marker M of a candidate gene. To each of the families is associated a covariate value; the families are ordered on the values of this covariate. As the TDT (Spielman et al. 1993), the OTDT is based on the observation of the transmission rate T of a given allele at M. The OTDT aims to find a critical value of the covariate which separates the sample of families in two subsamples in which the transmission rates are significantly different. We investigate the power of the method by simulations under various genetic models and covariate distributions. Acknowledgments H Perdry is funded by ARSEP. Pascal Croiseau 1 , Heather Cordell 2 , Emmanuelle Génin 134 INSERM U535 and University Paris Sud, UMR-S535, Villejuif, France 35 Institute of Human Genetics, Newcastle University, UK Keywords: Association, missing data, conditionnal logistic regression Missing data is an important problem in association studies. Several methods used to test for association need that individuals be genotyped at the full set of markers. Individuals with missing data need to be excluded from the analysis. This could involve an important decrease in sample size and a loss of information. If the disease susceptibility locus (DSL) is poorly typed, it is also possible that a marker in linkage disequilibrium gives a stronger association signal than the DSL. One may then falsely conclude that the marker is more likely to be the DSL. We recently developed a Multiple Imputation method to infer missing data on case-parent trios Starting from the observed data, a few number of complete data sets are generated by Markov-Chain Monte Carlo approach. These complete datasets are analysed using standard statistical package and the results are combined as described in Little & Rubin (2002). Here we report the results of simulations performed to examine, for different patterns of missing data, how often the true DSL gives the highest association score among different loci in LD. We found that multiple imputation usually correctly detect the DSL site even if the percentage of missing data is high. This is not the case for the naïve approach that consists in discarding trios with missing data. In conclusion, Multiple imputation presents the advantage of being easy to use and flexible and is therefore a promising tool in the search for DSL involved in complex diseases. Salma Kotti 1 , Heike Bickeböller 2 , Françoise Clerget-Darpoux 136 University Paris Sud, UMR-S535, Villejuif, France 37 Department of Genetic Epidemiology, Medical School, University of Göttingen, Germany Keywords: Genotype relative risk, internal controls, Family based analyses Family based analyses using internal controls are very popular both for detecting the effect of a genetic factor and for estimating the relative disease risk on the corresponding genotypes. Two different procedures are often applied to reconstitute internal controls. The first one considers one pseudocontrol genotype formed by the parental non-transmitted alleles called also 1:1 matching of alleles, while the second corresponds to three pseudocontrols corresponding to all genotypes formed by the parental alleles except the one of the case (1:3 matching). Many studies have compared between the two procedures in terms of the power and have concluded that the difference depends on the underlying genetic model and the allele frequencies. However, the estimation of the Genotype Relative Risk (GRR) under the two procedures has not been studied. Based on the fact that on the 1:1 matching, the control group is composed of the alleles untransmitted to the affected child and on the 1:3 matching, the control group is composed amongst alleles already transmitted to the affected child, we expect a difference on the GRR estimation. In fact, we suspect that the second procedure leads to biased estimation of the GRRs. We will analytically derive the GRR estimators for the 1:1 and 1:3 matching and will present the results at the meeting. Family based analyses using internal controls are very popular both for detecting the effect of a genetic factor and for estimating the relative disease risk on the corresponding genotypes. Two different procedures are often applied to reconstitute internal controls. The first one considers one pseudocontrol genotype formed by the parental non-transmitted alleles called also 1:1 matching of alleles, while the second corresponds to three pseudocontrols corresponding to all genotypes formed by the parental alleles except the one of the case (1:3 matching). Many studies have compared between the two procedures in terms of the power and have concluded that the difference depends on the underlying genetic model and the allele frequencies. However, the estimation of the Genotype Relative Risk (GRR) under the two procedures has not been studied. Based on the fact that on the 1:1 matching, the control group is composed of the alleles untransmitted to the affected child and on the 1:3 matching, the control group is composed amongst alleles already transmitted to the affected child, we expect a difference on the GRR estimation. In fact, we suspect that the second procedure leads to biased estimation of the GRR. We will analytically derive the GRR estimator for the 1:1 and 1:3 matching and will present the results at the meeting. Luigi Palla 1 , David Siegmund 239 Department of Mathematics,Free University Amsterdam, The Netherlands 40 Department of Statistics, Stanford University, California, USA Keywords: TDT, assortative mating, inbreeding, statistical power A substantial amount of Assortative Mating (AM) is often recorded on physical and psychological, dichotomous as well as quantitative traits that are supposed to have a multifactorial genetic component. In particular AM has the effect of increasing the genetic variance, even more than inbreeding because it acts across loci beside within loci, when the trait has a multifactorial origin. Under the assumption of a polygenic model for AM dating back to Wright (1921) and refined by Crow and Felsenstein (1968,1982), the effect of assortative mating on the power to detect genetic association in the Transmission Disequilibrium Test (TDT) is explored as parameters, such as the effective number of genes and the allelic frequency vary. The power is reflected by the non centrality parameter of the TDT and is expressed as a function of the number of trios, the relative risk of the heterozygous genotype and the allele frequency (Siegmund and Yakir, 2007). The noncentrality parameter of the relevant score statistic is updated considering the effect of AM which is expressed in terms of an ,effective' inbreeding coefficient. In particular, for dichotomous traits it is apparent that the higher the number of genes involved in the trait, the lower the loss in power due to AM. Finally an attempt is made to extend this relation to the Q-TDT (Rabinowitz, 1997), which involves considering the effect of AM also on the phenotypic variance of the trait of interest, under the assumption that AM affects only its additive genetic component. References Crow, & Felsenstein, (1968). The effect of assortative mating on the genetic composition of a population. Eugen.Quart.15, 87,97. Rabinowitz,, 1997. A Transmission Disequilibrium Test for Quantitative Trait Loci. Human Heredity47, 342,350. Siegmund, & Yakir, (2007) Statistics of gene mapping, Springer. Wright, (1921). System of mating.III. Assortative mating based on somatic resemblance. Genetics6, 144,161. Jérémie Nsengimana 1 , Ben D Brown 2 , Alistair S Hall 2 , Jenny H Barrett 141 Leeds Institute of Molecular Medicine, University of Leeds, UK 42 Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, UK Keywords: Inflammatory genes, haplotype, coronary artery disease Genetic Risk of Acute Coronary Events (GRACE) is an initiative to collect cases of coronary artery disease (CAD) and their unaffected siblings in the UK and to use them to map genetic variants increasing disease risk. The aim of the present study was to test the association between CAD and 51 single nucleotide polymorphisms (SNPs) and their haplotypes from 35 inflammatory genes. Genotype data were available for 1154 persons affected before age 66 (including 48% before age 50) and their 1545 unaffected siblings (891 discordant families). Each SNP was tested for association to CAD, and haplotypes within genes or gene clusters were tested using FBAT (Rabinowitz & Laird, 2000). For the most significant results, genetic effect size was estimated using conditional logistic regression (CLR) within STATA adjusting for other risk factors. Haplotypes were assigned using HAPLORE (Zhang et al., 2005), which considers all parental mating types consistent with offspring genotypes and assigns them a probability of occurence. This probability was used in CLR to weight the haplotypes. In the single SNP analysis, several SNPs showed some evidence for association, including one SNP in the interleukin-1A gene. Analysing haplotypes in the interleukin-1 gene cluster, a common 3-SNP haplotype was found to increase the risk of CAD (P = 0.009). In an additive genetic model adjusting for covariates the odds ratio (OR) for this haplotype is 1.56 (95% CI: 1.16-2.10, p = 0.004) for early-onset CAD (before age 50). This study illustrates the utility of haplotype analysis in family-based association studies to investigate candidate genes. References Rabinowitz, D. & Laird, N. M. (2000) Hum Hered50, 211,223. Zhang, K., Sun, F. & Zhao, H. (2005) Bioinformatics21, 90,103. Andrea Foulkes 1 , Recai Yucel 1 , Xiaohong Li 143 Division of Biostatistics, University of Massachusetts, USA Keywords: Haploytpe, high-dimensional, mixed modeling The explosion of molecular level information coupled with large epidemiological studies presents an exciting opportunity to uncover the genetic underpinnings of complex diseases; however, several analytical challenges remain to be addressed. Characterizing the components to complex diseases inevitably requires consideration of synergies across multiple genetic loci and environmental and demographic factors. In addition, it is critical to capture information on allelic phase, that is whether alleles within a gene are in cis (on the same chromosome) or in trans (on different chromosomes.) In associations studies of unrelated individuals, this alignment of alleles within a chromosomal copy is generally not observed. We address the potential ambiguity in allelic phase in this high dimensional data setting using mixed effects models. Both a semi-parametric and fully likelihood-based approach to estimation are considered to account for missingness in cluster identifiers. In the first case, we apply a multiple imputation procedure coupled with a first stage expectation maximization algorithm for parameter estimation. A bootstrap approach is employed to assess sensitivity to variability induced by parameter estimation. Secondly, a fully likelihood-based approach using an expectation conditional maximization algorithm is described. Notably, these models allow for characterizing high-order gene-gene interactions while providing a flexible statistical framework to account for the confounding or mediating role of person specific covariates. The proposed method is applied to data arising from a cohort of human immunodeficiency virus type-1 (HIV-1) infected individuals at risk for therapy associated dyslipidemia. Simulation studies demonstrate reasonable power and control of family-wise type 1 error rates. Vivien Marquard 1 , Lars Beckmann 1 , Jenny Chang-Claude 144 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany Keywords: Genotyping errors, type I error, haplotype-based association methods It has been shown in several simulation studies that genotyping errors may have a great impact on the type I error of statistical methods used in genetic association analysis of complex diseases. Our aim was to investigate type I error rates in a case-control study, when differential and non-differential genotyping errors were introduced in realistic scenarios. We simulated case-control data sets, where individual genotypes were drawn from a haplotype distribution of 18 haplotypes with 15 markers in the APM1 gene. Genotyping errors were introduced following the unrestricted and symmetric with 0 edges error models described by Heid et al. (2006). In six scenarios, errors resulted from changes of one allele to another with predefined probabilities of 1%, 2.5% or 10%, respectively. A multiple number of errors per haplotype was possible and could vary between 0 and 15, the number of markers investigated. We examined three association methods: Mantel statistics using haplotype-sharing; a haplotype-specific score test; and Armitage trend test for single markers. The type I error rates were not influenced for any of all the three methods for a genotyping error rate of less than 1%. For higher error rates and differential errors, the type I error of the Mantel statistic was only slightly and of the Armitage trend test moderately increased. The type I error rates of the score test were highly increased. The type I error rates were correct for all three methods for non-differential errors. Further investigations will be carried out with different frequencies of differential error rates and focus on power. Arne Neumann 1 , Dörthe Malzahn 1 , Martina Müller 2 , Heike Bickeböller 145 Department of Genetic Epidemiology, Medical School, University of Göttingen, Germany 46 GSF-National Research Center for Environment and Health, Neuherberg & IBE-Institute of Epidemiology, Ludwig-Maximilians University München, Germany Keywords: Interaction, longitudinal, nonparametric Longitudinal data show the time dependent course of phenotypic traits. In this contribution, we consider longitudinal cohort studies and investigate the association between two candidate genes and a dependent quantitative longitudinal phenotype. The set-up defines a factorial design which allows us to test simultaneously for the overall gene effect of the loci as well as for possible gene-gene and gene time interaction. The latter would induce genetically based time-profile differences in the longitudinal phenotype. We adopt a non-parametric statistical test to genetic epidemiological cohort studies and investigate its performance by simulation studies. The statistical test was originally developed for longitudinal clinical studies (Brunner, Munzel, Puri, 1999 J Multivariate Anal 70:286-317). It is non-parametric in the sense that no assumptions are made about the underlying distribution of the quantitative phenotype. Longitudinal observations belonging to the same individual can be arbitrarily dependent on one another for the different time points whereas trait observations of different individuals are independent. The two loci are assumed to be statistically independent. Our simulations show that the nonparametric test is comparable with ANOVA in terms of power of detecting gene-gene and gene-time interaction in an ANOVA favourable setting. Rebecca Hein 1 , Lars Beckmann 1 , Jenny Chang-Claude 147 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Germany Keywords: Indirect association studies, interaction effects, linkage disequilibrium, marker allele frequency Association studies accounting for gene-environment interactions (GxE) may be useful for detecting genetic effects and identifying important environmental effect modifiers. Current technology facilitates very dense marker spacing in genetic association studies; however, the true disease variant(s) may not be genotyped. In this situation, an association between a gene and a phenotype may still be detectable, using genetic markers associated with the true disease variant(s) (indirect association). Zondervan and Cardon [2004] showed that the odds ratios (OR) of markers which are associated with the disease variant depend highly on the linkage disequilibrium (LD) between the variant and the markers, and whether the allele frequencies match and thereby influence the sample size needed to detect genetic association. We examined the influence of LD and allele frequencies on the sample size needed to detect GxE in indirect association studies, and provide tables for sample size estimation. For discordant allele frequencies and incomplete LD, sample sizes can be unfeasibly large. The influence of both factors is stronger for disease loci with small rather than moderate to high disease allele frequencies. A decline in D' of e.g. 5% has less impact on sample size than increasing the difference in allele frequencies by the same percentage. Assuming 80% power, large interaction effects can be detected using smaller sample sizes than those needed for the detection of main effects. The detection of interaction effects involving rare alleles may not be possible. Focussing only on marker density can be a limited strategy in indirect association studies for GxE. Cyril Dalmasso 1 , Emmanuelle Génin 2 , Catherine Bourgain 2 , Philippe Broët 148 JE 2492 , Univ. Paris-Sud, France 49 INSERM UMR-S 535 and University Paris Sud, Villejuif, France Keywords: Linkage analysis, Multiple testing, False Discovery Rate, Mixture model In the context of genome-wide linkage analyses, where a large number of statistical tests are simultaneously performed, the False Discovery Rate (FDR) that is defined as the expected proportion of false discoveries among all discoveries is nowadays widely used for taking into account the multiple testing problem. Other related criteria have been considered such as the local False Discovery Rate (lFDR) that is a variant of the FDR giving to each test its own measure of significance. The lFDR is defined as the posterior probability that a null hypothesis is true. Most of the proposed methods for estimating the lFDR or the FDR rely on distributional assumption under the null hypothesis. However, in observational studies, the empirical null distribution may be very different from the theoretical one. In this work, we propose a mixture model based approach that provides estimates of the lFDR and the FDR in the context of large-scale variance component linkage analyses. In particular, this approach allows estimating the empirical null distribution, this latter being a key quantity for any simultaneous inference procedure. The proposed method is applied on a real dataset. Arief Gusnanto 1 , Frank Dudbridge 150 MRC Biostatistics Unit, Cambridge UK Keywords: Significance, genome-wide, association, permutation, multiplicity Genome-wide association scans have introduced statistical challenges, mainly in the multiplicity of thousands of tests. The question of what constitutes a significant finding remains somewhat unresolved. Permutation testing is very time-consuming, whereas Bayesian arguments struggle to distinguish direct from indirect association. It seems attractive to summarise the multiplicity in a simple form that allows users to avoid time-consuming permutations. A standard significance level would facilitate reporting of results and reduce the need for permutation tests. This is potentially important because current scans do not have full coverage of the whole genome, and yet, the implicit multiplicity is genome-wide. We discuss some proposed summaries, with reference to the empirical null distribution of the multiple tests, approximated through a large number of random permutations. Using genome-wide data from the Wellcome Trust Case-Control Consortium, we use a sub-sampling approach with increasing density to estimate the nominal p-value to obtain family-wise significance of 5%. The results indicate that the significance level is converging to about 1e-7 as the marker spacing becomes infinitely dense. We considered the concept of an effective number of independent tests, and showed that when used in a Bonferroni correction, the number varies with the overall significance level, but is roughly constant in the region of interest. We compared several estimators of the effective number of tests, and showed that in the region of significance of interest, Patterson's eigenvalue based estimator gives approximately the right family-wise error rate. Michael Nothnagel 1 , Amke Caliebe 1 , Michael Krawczak 151 Institute of Medical Informatics and Statistics, University Clinic Schleswig-Holstein, University of Kiel, Germany Keywords: Association scans, Bayesian framework, posterior odds, genetic risk, multiplicative model Whole-genome association scans have been suggested to be a cost-efficient way to survey genetic variation and to map genetic disease factors. We used a Bayesian framework to investigate the posterior odds of a genuine association under multiplicative disease models. We demonstrate that the p value alone is not a sufficient means to evaluate the findings in association studies. We suggest that likelihood ratios should accompany p values in association reports. We argue, that, given the reported results of whole-genome scans, more associations should have been successfully replicated if the consistently made assumptions about considerable genetic risks were correct. We conclude that it is very likely that the vast majority of relative genetic risks are only of the order of 1.2 or lower. Clive Hoggart 1 , Maria De Iorio 1 , John Whittakker 2 , David Balding 152 Department of Epidemiology and Public Health, Imperial College London, UK 53 Department of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, UK Keywords: Genome-wide association analyses, shrinkage priors, Lasso Testing one SNP at a time does not fully realise the potential of genome-wide association studies to identify multiple causal variants of small effect, which is a plausible scenario for many complex diseases. Moreover, many simulation studies assume a single causal variant and so more complex realities are ignored. Analysing large numbers of variants simultaneously is now becoming feasible, thanks to developments in Bayesian stochastic search methods. We pose the problem of SNP selection as variable selection in a regression model. In contrast to single SNP tests this approach simultaneously models the effect of all SNPs. SNPs are selected by a Bayesian interpretation of the lasso (Tibshirani, 1996); the maximum a posterior (MAP) estimate of the regression coefficients, which have been given independent, double exponential prior distributions. The double exponential distribution is an example of a shrinkage prior, MAP estimates with shrinkage priors can be zero, thus all SNPs with non zero regression coefficients are selected. In addition to the commonly-used double exponential (Laplace) prior, we also implement the normal exponential gamma prior distribution. We show that use of the Laplace prior improves SNP selection in comparison with single -SNP tests, and that the normal exponential gamma prior leads to a further improvement. Our method is fast and can handle very large numbers of SNPs: we demonstrate its performance using both simulated and real genome-wide data sets with 500 K SNPs, which can be analysed in 2 hours on a desktop workstation. Mickael Guedj 1,2 , Jerome Wojcik 2 , Gregory Nuel 154 Laboratoire Statistique et Génome, Université d'Evry, Evry France 55 Serono Pharmaceutical Research Institute, Plan-les-Ouates, Switzerland Keywords: Local Replication, Local Score, Association In gene-mapping, replication of initial findings has been put forwards as the approach of choice for filtering false-positives from true signals for underlying loci. In practice, such replications are however too poorly observed. Besides the statistical and technical-related factors (lack of power, multiple-testing, stratification, quality control,) inconsistent conclusions obtained from independent populations might result from real biological differences. In particular, the high degree of variation in the strength of LD among populations of different origins is a major challenge to the discovery of genes. Seeking for Local Replications (defined as the presence of a signal of association in a same genomic region among populations) instead of strict replications (same locus, same risk allele) may lead to more reliable results. Recently, a multi-markers approach based on the Local Score statistic has been proposed as a simple and efficient way to select candidate genomic regions at the first stage of genome-wide association studies. Here we propose an extension of this approach adapted to replicated association studies. Based on simulations, this method appears promising. In particular it outperforms classical simple-marker strategies to detect modest-effect genes. Additionally it constitutes, to our knowledge, a first framework dedicated to the detection of such Local Replications. Juliet Chapman 1 , Claudio Verzilli 1 , John Whittaker 156 Department of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, UK Keywords: FDR, Association studies, Bayesian model selection As genomewide association studies become commonplace there is debate as to how such studies might be analysed and what we might hope to gain from the data. It is clear that standard single locus approaches are limited in that they do not adjust for the effects of other loci and problematic since it is not obvious how to adjust for multiple comparisons. False discovery rates have been suggested, but it is unclear how well these will cope with highly correlated genetic data. We consider the validity of standard false discovery rates in large scale association studies. We also show that a Bayesian procedure has advantages in detecting causal loci amongst a large number of dependant SNPs and investigate properties of a Bayesian FDR. Peter Kraft 157 Harvard School of Public Health, Boston USA Keywords: Gene-environment interaction, genome-wide association scans Appropriately analyzed two-stage designs,where a subset of available subjects are genotyped on a genome-wide panel of markers at the first stage and then a much smaller subset of the most promising markers are genotyped on the remaining subjects,can have nearly as much power as a single-stage study where all subjects are genotyped on the genome-wide panel yet can be much less expensive. Typically, the "most promising" markers are selected based on evidence for a marginal association between genotypes and disease. Subsequently, the few markers found to be associated with disease at the end of the second stage are interrogated for evidence of gene-environment interaction, mainly to understand their impact on disease etiology and public health impact. However, this approach may miss variants which have a sizeable effect restricted to one exposure stratum and therefore only a modest marginal effect. We have proposed to use information on the joint effects of genes and a discrete list of environmental exposures at the initial screening stage to select promising markers for the second stage [Kraft et al Hum Hered 2007]. This approach optimizes power to detect variants that have a sizeable marginal effect and variants that have a small marginal effect but a sizeable effect in a stratum defined by an environmental exposure. As an example, I discuss a proposed genome-wide association scan for Type II diabetes susceptibility variants based in several large nested case-control studies. Beate Glaser 1 , Peter Holmans 158 Biostatistics and Bioinformatics Unit, Cardiff University, School of Medicine, Heath Park, Cardiff, UK Keywords: Combined case-control and trios analysis, Power, False-positive rate, Simulation, Association studies The statistical power of genetic association studies can be enhanced by combining the analysis of case-control with parent-offspring trio samples. Various combined analysis techniques have been recently developed; as yet, there have been no comparisons of their power. This work was performed with the aim of identifying the most powerful method among available combined techniques including test statistics developed by Kazeem and Farrall (2005), Nagelkerke and colleagues (2004) and Dudbridge (2006), as well as a simple combination of ,2-statistics from single samples. Simulation studies were performed to investigate their power under different additive, multiplicative, dominant and recessive disease models. False-positive rates were determined by studying the type I error rates under null models including models with unequal allele frequencies between the single case-control and trios samples. We identified three techniques with equivalent power and false-positive rates, which included modifications of the three main approaches: 1) the unmodified combined Odds ratio estimate by Kazeem & Farrall (2005), 2) a modified approach of the combined risk ratio estimate by Nagelkerke & colleagues (2004) and 3) a modified technique for a combined risk ratio estimate by Dudbridge (2006). Our work highlights the importance of studies investigating test performance criteria of novel methods, as they will help users to select the optimal approach within a range of available analysis techniques. David Almorza 1 , M.V. Kandus 2 , Juan Carlos Salerno 2 , Rafael Boggio 359 Facultad de Ciencias del Trabajo, University of Cádiz, Spain 60 Instituto de Genética IGEAF, Buenos Aires, Argentina 61 Universidad Nacional de La Plata, Buenos Aires, Argentina Keywords: Principal component analysis, maize, ear weight, inbred lines The objective of this work was to evaluate the relationship among different traits of the ear of maize inbred lines and to group genotypes according to its performance. Ten inbred lines developed at IGEAF (INTA Castelar) and five public inbred lines as checks were used. A field trial was carried out in Castelar, Buenos Aires (34° 36' S , 58° 39' W) using a complete randomize design with three replications. At harvest, individual weight (P.E.), diameter (D.E.), row number (N.H.) and length (L.E.) of the ear were assessed. A principal component analysis, PCA, (Infostat 2005) was used, and the variability of the data was depicted with a biplot. Principal components 1 and 2 (CP1 and CP2) explained 90% of the data variability. CP1 was correlated with P.E., L.E. and D.E., meanwhile CP2 was correlated with N.H. We found that individual weight (P.E.) was more correlated with diameter of the ear (D.E.) than with length (L.E). Five groups of inbred lines were distinguished: with high P.E. and mean N.H. (04-70, 04-73, 04-101 and MO17), with high P.E. but less N.H. (04-61 and B14), with mean P.E. and N.H. (B73, 04-123 and 04-96), with high N.H. but less P.E. (LP109, 04-8, 04-91 and 04-76) and with low P.E. and low N.H. (LP521 and 04-104). The use of PCA showed which variables had more incidence in ear weight and how is the correlation among them. Moreover, the different groups found with this analysis allow the evaluation of inbred lines by several traits simultaneously. Sven Knüppel 1 , Anja Bauerfeind 1 , Klaus Rohde 162 Department of Bioinformatics, MDC Berlin, Germany Keywords: Haplotypes, association studies, case-control, nuclear families The area of gene chip technology provides a plethora of phase-unknown SNP genotypes in order to find significant association to some genetic trait. To circumvent possibly low information content of a single SNP one groups successive SNPs and estimates haplotypes. Haplotype estimation, however, may reveal ambiguous haplotype pairs and bias the application of statistical methods. Zaykin et al. (Hum Hered, 53:79-91, 2002) proposed the construction of a design matrix to take this ambiguity into account. Here we present a set of functions written for the Statistical package R, which carries out haplotype estimation on the basis of the EM-algorithm for individuals (case-control) or nuclear families. The construction of a design matrix on basis of estimated haplotypes or haplotype pairs allows application of standard methods for association studies (linear, logistic regression), as well as statistical methods as haplotype sharing statistics and TDT-Test. Applications of these methods to genome-wide association screens will be demonstrated. Manuela Zucknick 1 , Chris Holmes 2 , Sylvia Richardson 163 Department of Epidemiology and Public Health, Imperial College London, UK 64 Department of Statistics, Oxford Center for Gene Function, University of Oxford, UK Keywords: Bayesian, variable selection, MCMC, large p, small n, structured dependence In large-scale genomic applications vast numbers of markers or genes are scanned to find a few candidates which are linked to a particular phenotype. Statistically, this is a variable selection problem in the "large p, small n" situation where many more variables than samples are available. An additional feature is the complex dependence structure which is often observed among the markers/genes due to linkage disequilibrium or their joint involvement in biological processes. Bayesian variable selection methods using indicator variables are well suited to the problem. Binary phenotypes like disease status are common and both Bayesian probit and logistic regression can be applied in this context. We argue that logistic regression models are both easier to tune and to interpret than probit models and implement the approach by Holmes & Held (2006). Because the model space is vast, MCMC methods are used as stochastic search algorithms with the aim to quickly find regions of high posterior probability. In a trade-off between fast-updating but slow-moving single-gene Metropolis-Hastings samplers and computationally expensive full Gibbs sampling, we propose to employ the dependence structure among the genes/markers to help decide which variables to update together. Also, parallel tempering methods are used to aid bold moves and help avoid getting trapped in local optima. Mixing and convergence of the resulting Markov chains are evaluated and compared to standard samplers in both a simulation study and in an application to a gene expression data set. Reference Holmes, C. C. & Held, L. (2006) Bayesian auxiliary variable models for binary and multinomial regression. Bayesian Analysis1, 145,168. Dawn Teare 165 MMGE, University of Sheffield, UK Keywords: CNP, family-based analysis, MCMC Evidence is accumulating that segmental copy number polymorphisms (CNPs) may represent a significant portion of human genetic variation. These highly polymorphic systems require handling as phenotypes rather than co-dominant markers, placing new demands on family-based analyses. We present an integrated approach to meet these challenges in the form of a graphical model, where the underlying discrete CNP phenotype is inferred from the (single or replicate) quantitative measure within the analysis, whilst assuming an allele based system segregating through the pedigree. [source] Professionalization, Gender and Female-dominated Professions: Dental Hygiene in Ontario,CANADIAN REVIEW OF SOCIOLOGY/REVUE CANADIENNE DE SOCIOLOGIE, Issue 3 2003TRACEY L. ADAMS Cet article explore L'influence des rapports sociaux entre les sexes et du féminisme sur les professions à majorité féminine au moyen d'une étude de cas en hygiène dentaire en Ontario. Le statut professionnel à part entière a échappéà plusieurs de ces professions, y compris L'hygiène dentaire. Historiquement, cette dernière était définie comme un travail pour les femmes, àêtre exécuté sous la stricte surveillance des dentistes hommes. Récemment, L'hygiène dentaire a poursuivi un projet de reconnaissance professionnelle et lutté pour une plus grande indépendance à L'endroit de la dentisterie. Les idées issues des rapports sociaux entre les sexes et particulièrement du féminisme y ont occupé une place centrale. This paper explores the influence of gender and feminism on the professional projects of female-dominated professions, through a case study of dental hygiene in Ontario. Full professional status has eluded many female-dominated professions, including dental hygiene. Historically, dental hygiene was defined as work for women, to be performed strictly under the control of male dentists. In recent years, dental hygiene has pursued a professional project and struggled for greater independence from dentistry. Ideas about gender and, particularly, feminism have been central to their professional project. [source] Biopolymere in textilen Anwendungen.CHEMIE IN UNSERER ZEIT (CHIUZ), Issue 3 2009Polyhydroxyalkanoate, Polylactid Abstract Biopolymere stellen eine interessante Polymerklasse dar, deren Potential bisher noch nicht endgültig erfasst ist. Sie gewinnen jedoch zunehmend an Marktwert. Vor allem Polylactid (PLA) hat sich bereits durchsetzen können, da es nicht nur aus nachwachsenden Rohstoffen hergestellt werden kann und abbaubar ist, sondern darüber hinaus ein Eigenschaftsprofil aufweist, das mit herkömmlichen thermoplastischen Kunststoffen vergleichbar ist und sich auch ähnlich gut verarbeiten lässt. Das Anwendungsfeld der Biopolymere reicht von Folien, Obst- und Gemüseschalen bis hin zu Hygiene- und Medizinartikeln und ist daher sehr vielfältig. Diese Vielfältigkeit wird sicherlich in der Zukunft weiter zunehmen. Biopolymers represent an interesting class of polymers whose potential is not yet been fully realised. However, more recently, biopolymers are gaining impetus in the market. Among the biopolymers, polylactic acid (PLA) is being used successfully and is widely accepted because it is produced from natural raw material and is degradable. Furthermore, it has comparable properties to standard thermoplastic polymers and can also be processed using similar process channels as conventional thermoplastic synthetic materials. Biopolymer applications are manifold and range from foils, fruit and vegetable packaging to hygiene and medical products. It can be expected that in future the application spectrum of biopolymers will increase even further. [source] Impact of Wearable Alcohol Gel Dispensers on Hand Hygiene in an Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 4 2008Janet P. Haas RN Abstract Objectives:, Compliance with hand hygiene (HH) by health care workers is widely recognized as the most effective way to decrease transmission of infection among patients. However, compliance remains poor, averaging about 40%. A potential barrier to compliance is convenience and accessibility of sinks or alcohol hand sanitizer dispensers. The purpose of this study was to assess the use of a personal alcohol gel dispensing system, compared with the traditional wall-mounted alcohol gel dispenser and sinks in an urban hospital's emergency department (ED). Methods:, This was a quasi-experimental trial of a personal wearable alcohol hand sanitizer dispenser. Observations of ED staff HH were performed in the month before intervention and during three intervention phases over a 2.5-month period. Results:, A total of 757 HH opportunities were observed: 112 before and 432 after patient contact, 72 after contact with the patient's environment, 24 before invasive procedures, and 117 after body fluid contact. HH compliance improved during the first intervention period, but improvement was not sustained. There was no significant improvement in HH from baseline to the final intervention period. The wearable alcohol gel dispenser was used for 9% of HH episodes. Conclusions:, Availability of a wearable dispenser was not associated with a significant improvement in use of alcohol products for HH. These results support other studies in which only transient success was reported with a single intervention; greater success in sustaining increased HH compliance has been reported with use of multimodal approaches in which increased availability of products may be a part of the intervention. [source] Contact allergy to sodium cocoamphoacetate present in an eye make-up removerCONTACT DERMATITIS, Issue 5 2006A. Goossens This is a case report of a contact allergic reaction on the face due to a skin cleansing product containing the amphoteric surfactant sodium cocoamphoacetate, occurring in an atopic woman with multiple contact sensitivities. Because of its weak irritant properties, this surfactant is widely used in cosmetic products intended to be used for sensitive skin, including products for intimate, and baby hygiene. [source] The Creation of Emergency Health Care Standards for Catastrophic EventsACADEMIC EMERGENCY MEDICINE, Issue 11 2006Robert A. Wise MD The creation of health care standards by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) in a defined area with known events follows a predictable process. A problem area (e.g., hand hygiene) is identified from multiple sources. The JCAHO then calls together experts from around the country, and through debate and the comparison of positions of various people within the health care arena, a new standard informed by these views can be developed. Once developed, it is vetted and becomes established as a Joint Commission standard. But what happens when an event has never happened, cannot be reliably predicted, and, one hopes, will never come to pass? How can one create any meaningful standards? This is the situation when considering a number of scenarios related to disasters and mass casualty events. [source] Orthopaedic issues in the musculoskeletal care of adults with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2009HELEN M HORSTMANN MD Aims, Orthopaedic care of adults with cerebral palsy (CP) has not been well documented in orthopaedic literature. This paper focuses on some of the common problems which present themselves when adults with CP seek orthopaedic intervention. In particular, we review the most common orthopaedic issues which present to the Penn Neuro-Orthopaedics Program. Method, A formal review of consecutive surgeries performed by the senior author on adults with CP was previously conducted. This paper focuses on the health delivery care for the adult with orthopaedic problems related to cerebral palsy. Ninety-two percent of these patients required lower extremity surgery. Forty percent had procedures performed on the upper extremities. Results, The majority of problems seen in the Penn Neuro-Orthopaedics Program are associated with the residuals of childhood issues, particularly deformities associated with contractures. Patients are also referred for treatment of acquired musculoskeletal problems such as degenerative arthritis of the hip or knee. A combination of problems contribute most frequently to foot deformities and pain with weight-bearing, shoewear or both, most often due to equinovarus. The surgical correction of this is most often facilitated through a split anterior tibial tendon transfer. Posterior tibial transfers are rarely indicated. Residual equinus deformities contribute to a pes planus deformity. The split anterior tibial tendon transfer is usually combined with gastrocnemius-soleus recession and plantar release. Transfer of the flexor digitorum longus to the os calcis is done to augment the plantar flexor power. Rigid pes planus deformity is treated with a triple arthrodesis. Resolution of deformity allows for a good base for standing, improved ability to tolerate shoewear, and/or braces. Other recurrent or unresolved issues involve hip and knee contractures. Issues of lever arm dysfunction create problems with mechanical inefficiency. Upper extremity intervention is principally to correct contractures. Internal rotation and adductor tightness at the shoulder makes for difficult underarm hygiene and predispose a patient to a spiral fracture of the humerus. A tight flexor, pronation pattern is frequently noted through the elbow and forearm with further flexion contractures through the wrist and fingers. Lengthenings are more frequently performed than tendon transfers in the upper extremity. Arthrodesis of the wrist or on rare occasions of the metacarpal-phalangeal joints supplement the lengthenings when needed. Conclusions, The Penn Neuro-Orthopaedics Program has successfully treated adults with both residual and acquired musculoskeletal deformities. These deformities become more critical when combined with degenerative changes, a relative increase in body mass, fatigue, and weakness associated with the aging process. [source] Proximal femoral resection for subluxation or dislocation of the hip in spastic quadriplegiaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2003Steve Ackerly MD Management of a painful or contracted hip dislocation in individuals with severe spastic quadriplegia is difficult. Clinical and radiographic results of 12 proximal femoral resection-interposition operations performed in seven non-ambulatory persons (five males, two females; mean age 14 years, 8 months; age range 6 years 11 months to 19 years 8 months) with severe spasticity were reviewed to determine if pain relief and restoration of motion were maintained. At a mean follow-up of 7 years 7 months (median 9 years 6 months) all participants maintained a good sitting position and a functional range of motion with improved hygiene. Hip pain was improved in all participants compared with their preoperative status. Proximal femur migration occurred causing slight pain in one person. Heterotopic ossification was observed but was not clinically significant. Complications included traction pin loosening and infection and a late supracondylar femur fracture 3 months after the operation. Proximal femoral resection effectively decreased pain and restored hip motion in those with severe spastic quadriplegia leading to improved sitting and perineal care. [source] The oral health of street-recruited injecting drug users: prevalence and correlates of problemsADDICTION, Issue 11 2008Anne-Marie Laslett ABSTRACT Aims To examine the effects of a series of injecting drug users' (IDU) characteristics and drug use behaviours upon the self-reported oral health of a sample of IDU. Design Cross-sectional survey. Setting Melbourne, Australia. Participants A total of 285 IDU recruited through needle and syringe programmes, snowballing and outreach across six sites. Measurements Structured survey that collected information on current drug use patterns, self-reported blood-borne virus status and general health factors, including open-ended questions on past-year dental health problems. Findings Sixty-eight per cent of the sample reported dental problems that were commonly severe and caused dental pain. Despite these reported problems, almost half the sample had not visited the dentist in the 12 months prior to the survey. Participants who were older, and reported homelessness, not eating every day and more common injection of amphetamines rather than heroin in the previous month, were more likely to report having a past-year dental problem. Conclusions Dental problems in IDUs are common but few receive treatment. Further, those using amphetamines, with poor housing, hygiene and poor nutrition, are most at risk. Programmes designed to improve the oral health of IDU need to be developed and implemented in a manner amenable to the varying social circumstances of this marginalized group in the community. [source] The ,Malbouffe' Saga La Saga de la ,Malbouffe' Die Saga von ,Malbouffe"EUROCHOICES, Issue 1 2007Alain Rérat summary The ,Malbouffe' Saga After the end of the Second World War, a marked increase in animal and plant production was observed in France, little by little considered by consumers to be obtained at the expense of product quality. The pejorative term ,malbouffe' soon emerged, in connection not only with the hygiene of food, but also with its organoleptic and technological characteristics. This article focuses on food safety in France, with special attention paid to the incidence of toxi-infections and food contaminations of biological and chemical origin. The Mad Cow outbreak is reviewed, along with its consequences for human health in the form of new variant Creutzfeldt-Jakob's disease. It is emphasized that food-related human mortality , almost exclusively due to biological contaminations , represented only 647 cases in 1995, i.e., 0.12 per cent of the overall mortality rate. The main contaminants were Salmonella, whose number is steadily decreasing, and Campylobacter, but parasite and phycotoxic risks are increasing. Mortality due to chemical contaminants is very low i.e., 10 cases or 0.002 per cent of overall mortality These contaminants, either accidental (dioxin, hydrocarbons, radioactive isotopes) or unavoidable (residues from phytochemicals, fertilisers) may be at the source of acute or chronic intoxications with sometimes unknown consequences. Nevertheless, food safety in France does not merit the spiteful term ,malbouffe'. Nach dem Ende des Zweiten Weltkriegs war in Frankreich im Bereich der Tier- und Pflanzenproduktion ein deutlicher Zuwachs zu beobachten, welcher in den Augen der Verbraucher zunehmend auf Kosten der Produktqualität erreicht wurde. Der abwertende Begriff ,Malbouffe" (in etwa ,schlechtes Essen") entstand bald darauf nicht nur im Hinblick auf die Nahrungsmittelhygiene, sondern auch in Bezug auf die organoleptischen und technologischen Eigenschaften der Nahrungsmittel. Dieser Beitrag konzentriert sich auf die Nahrungsmittelsicherheit in Frankreich unter besonderer Berücksichtigung der aufgetretenen Infektionen durch Giftstoffe und der Kontamination von Nahrungsmitteln biologischen und chemischen Ursprungs. Der BSE-Ausbruch und dessen Auswirkungen auf die Gesundheit des Menschen in Form von einer neuen Variante der Creutzfeldt-Jakob-Krankheit werden noch einmal betrachtet. Es wird hervor gehoben, dass die nahrungsmittelbedingte Sterblichkeit bei Menschen, die nahezu ausschließlich auf biologische Kontaminationen zurückzuführen ist, 1995 bei nur 647 Fällen lag, d.h. bei 0,12 Prozent der gesamten Sterblichkeitsrate. Die Nahrungsmittel wurden hauptsächlich durch Salmonellen (die Anzahl dieser Fälle nimmt kontinuierlich ab) und Campylobacter kontaminiert, die parasitären und phykotoxischen Risiken nehmen jedoch zu. Die auf chemische Kontaminationen zurückzuführende Sterblichkeit ist sehr gering und macht zehn Fälle oder 0,002 Prozent der gesamten Sterblichkeitsrate aus. Bei diesen Kontaminationen, die entweder zufällig herbei geführt werden (durch Dioxin, Kohlenwasserstoff, radioaktive Isotope) oder unvermeidbar sind (durch Rückstände pfl anzenchemischer Substanzen, Düngemittel), könnte es sich um die Ursache für akute oder chronische Vergiftungen handeln, welche zum Teil unbekannte Konsequenzen nach sich ziehen. Dennoch hat die Nahrungsmittelsicherheit in Frankreich den verächtlichen Begriff ,Malbouffe" nicht verdient. Après la fi n de la deuxième guerre mondiale, l'agriculture française a connu une augmentation spectaculaire des rendements des productions animale et végétale, rapidement accusée d'avoir été obtenue aux dépens de la qualité des produits consommés. Ainsi est apparue le terme barbare de «malbouffe», lié dans l'esprit des consommateurs, non seulement aux qualités hygiéniques de l'alimentation, mais également à ses caractéristiques sensorielles, voire technologiques. Ce rapport se focalise uniquement sur la salubrité alimentaire en France, soulignant, en particulier, l'évolution de l'incidence des toxi-infections et des contaminations alimentaires d'origine biologique et chimique. Après avoir rappelé l'épizootie de la vache folle (1000 cas en France depuis 1996 et actuellement en cours d'extinction) et de ses conséquences sur la santé humaine (nouvelle variante de la maladie de Creutzfeldt-Jakob) limitées actuellement à 13 cas mortels dans notre pays, ce rapport précise que la mortalité humaine liée à l'alimentation , presque totalement due à des contaminations biologiques - ne représentait en 1995 que 647 cas, i.e. 0.12% de la mortalité générale. Pour l'essentiel, ces contaminants sont des salmonelles, en baisse constante, et des campylobacter, mais on peut craindre la progression des risques parasitaires et phycotoxiques, encore réduits actuellement. La mortalité liée aux contaminants chimiques est très faible (10 cas, i.e. 0.002% de la mortalité générale); mais ces contaminants -qu'ils soient accidentels (dioxine, hydrocarbures, isotopes radio-actifs,) ou inévitables (résidus de phytosanitaires, d'engrais,)- peuvent être à l'origine de crises aiguës ou d'intoxications chroniques dont on ne connaît pas toujours les implications. Néanmoins, dans l'ensemble, la salubrité alimentaire en France ne mérite nullement la connotation malveillante du terme «malbouffe». [source] Experiences of oral care in patients with haematological malignancies or head and neck cancerEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2003ASSISTANT PROFESSOR , K.E.O. ÖHRN RDH The aim of the present study was to investigate cancer patients' experiences of oral hygiene information, oral care and self-care, information on oral complications, examination of the oral cavity, and ability to eat and drink during cancer treatment, and to explore patient attitudes to oral examination and oral hygiene. The sample consisted of 41 consecutive patients treated with radiotherapy for head and neck cancer (n = 18) or with chemotherapy for haematological malignancies (n = 23). Patients were interviewed at the end of radiotherapy or the second/third chemotherapy cycle. Compared with patients receiving chemotherapy, those who received radiotherapy had significantly more often visited hospital dentistry, been informed about oral complications and oral hygiene, received instructions in oral hygiene procedures, and been examined by hospital staff. More of the radiotherapy patients experienced oral symptoms and difficulties to eat and drink during treatment. There were no significant differences between the groups with regard to patient experiences of the oral hygiene procedures. Only one patient objected to having hospital staff discuss oral hygiene procedures, and three did not want hospital staff to examine their oral cavity. Patients undergoing radiotherapy or chemotherapy need to be monitored during treatment with regard to their oral status and oral symptoms and complications. There are no acceptable reasons for allowing patients to suffer from oral symptoms that can be reduced. [source] Factors influencing the caries decline in Lithuanian adolescents , trends in the period 1993,2001EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 1 2004Jolanta Aleksej The study aimed to relate a number of factors to the numbers of decayed, missing and filled teeth (DMFT) in 12- and 15-yr-olds examined and interviewed in 1993 and 2001. A total of 1250 children in 1993 and 935 in 2001 were clinically examined and completed a detailed questionnaire on dental health-related topics. Factors were related to the DMFT count applying multiple regression analysis. From 1993 to 2001, the mean DMFT decreased approximately 30% in both age cohorts. Despite an observed improvement in dental health in Lithuanian children, the number of Lithuanian children reporting frequent sugar consumption, brushing teeth irregularly and visiting the dentist only in case of emergency was still high compared with Western countries. The DMFT values were related to the fluoride content in the drinking water, oral hygiene, residency and year of examination. [source] Effects of prolonged gum chewing on pain and fatigue in human jaw musclesEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2001Mauro Farella Gum chewing has been accepted as an adjunct to oral hygiene, as salivary stimulant and vehicle for various agents, as well as for jaw muscle training. The aim of this study was to investigate the effects of prolonged gum chewing on pain, fatigue and pressure tenderness of the masticatory muscles. Fifteen women without temporomandibular disorders (TMD) were requested to perform one of the following chewing tasks in three separate sessions: chewing a very hard gum, chewing a soft gum, and empty-chewing with no bolus. Unilateral chewing of gum or empty chewing was performed for 40 min at a constant rate of 80 cycles/min. In each session, perceived muscle pain and masticatory fatigue were rated on visual analog scales (VAS) before, throughout, and after the chewing task. Pressure pain thresholds (PPTs) of masseter and anterior temporalis muscles were assessed before and immediately after the chewing tasks, and again after 24 h. The VAS scores for pain and fatigue significantly increased only during the hard gum chewing, and after 10 min of recovery VAS scores had decreased again, almost to their baseline values. No significant changes were found for PPTs either after hard or soft gum chewing. The findings indicate that the jaw muscles recover quickly from prolonged chewing activity in subjects without TMD. [source] An epidemiological study on the occurrence of Staphylococcus aureus in superficial abscesses of patients presenting for surgery in a teaching hospital in Khartoum, SudanFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2000Seif Eldin Ibrahim Mahdi Abstract A group of patients (n=86) suffering from superficial abscesses was recruited in the Khartoum Teaching Hospital, Sudan. Detailed clinical and socio-economic data were collected. It appeared that 83% of all patients were younger than 40. Labourers were most prevalent (28%), followed by students (23%) and housewives (16%). The head and neck were most often affected (22%), with hands being second (19%). In 92% of all pus cultures a microbial agents was identified, the large majority being Staphylococcus aureus (69%). Among patients, 47% were nasal carriers of S. aureus, similar to the carriage rate measured among controls, suggesting that nasal carriage is no risk factor for abscess development. Multivariate logistic regression analysis revealed that a history of abscess, recent traditional medical treatment, poor hygiene and low socio-economic status were significantly and independently associated with the occurrence of superficial abscesses. [source] Bacterial silver resistance: molecular biology and uses and misuses of silver compoundsFEMS MICROBIOLOGY REVIEWS, Issue 2-3 2003Simon Silver Abstract Resistance to silver compounds as determined by bacterial plasmids and genes has been defined by molecular genetics. Silver resistance conferred by the Salmonella plasmid pMGH100 involves nine genes in three transcription units. A sensor/responder (SilRS) two-component transcriptional regulatory system governs synthesis of a periplasmic Ag(I)-binding protein (SilE) and two efflux pumps (a P-type ATPase (SilP) plus a three-protein chemiosmotic RND Ag(I)/H+ exchange system (SilCBA)). The same genes were identified on five of 19 additional IncH incompatibility class plasmids but thus far not on other plasmids. Of 70 random enteric isolates from a local hospital, isolates from catheters and other Ag-exposed sites, and total genomes of enteric bacteria, 10 have recognizable sil genes. The centrally located six genes are found and functional in the chromosome of Escherichia coli K-12, and also occur on the genome of E. coli O157:H7. The use of molecular epidemiological tools will establish the range and diversity of such resistance systems in clinical and non-clinical sources. Silver compounds are used widely as effective antimicrobial agents to combat pathogens (bacteria, viruses and eukaryotic microorganisms) in the clinic and for public health hygiene. Silver cations (Ag+) are microcidal at low concentrations and used to treat burns, wounds and ulcers. Ag is used to coat catheters to retard microbial biofilm development. Ag is used in hygiene products including face creams, ,alternative medicine' health supplements, supermarket products for washing vegetables, and water filtration cartridges. Ag is generally without adverse effects for humans, and argyria (irreversible discoloration of the skin resulting from subepithelial silver deposits) is rare and mostly of cosmetic concern. [source] |