Prevalence and characteristics of periodic leg movements during sleep in the general population : the Hypnolaus study

Objective: The aim of this study was to describe the prevalence and characteristics of periodic legs movements of sleep (PLMS) in theadult general population. Methods: Data from 2162 subjects (51.2% women, mean SD age:58, 11 years, range: 40.5-84.4 years) participating in a population-based cohort study (HypnoLaus, Lausanne, Switzerland) wascollected. They completed a series of sleep related questionnaires and underwent polysomnographic recordings at home. PLMS index(PLMSI) was determined according to AASM 2007 criteria. APLMSI>15/h was considered to be of potential clinical significance. Conclusions: PLMS are highly prevalent in the general population. Age, male gender and RLS are independent predictors of a PLMSIhigher than 15/h. Further studies are needed to evaluate the clinical impact of PLMS.

Life partnerships in childhood cancer survivors, their siblings, and the general population.

BACKGROUND: Life partnerships other than marriage are rarely studied in childhood cancer survivors (CCS). We aimed (1) to describe life partnership and marriage in CCS and compare them to life partnerships in siblings and the general population; and (2) to identify socio-demographic and cancer-related factors associated with life partnership and marriage. METHODS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to all CCS (aged 20-40 years) registered in the Swiss Childhood Cancer Registry (SCCR), aged <16 years at diagnosis, who had survived ≥ 5 years. The proportion with life partner or married was compared between CSS and siblings and participants in the Swiss Health Survey (SHS). Multivariable logistic regression was used to identify factors associated with life partnership or marriage. RESULTS: We included 1,096 CCS of the SCCSS, 500 siblings and 5,593 participants of the SHS. Fewer CCS (47%) than siblings (61%, P < 0.001) had life partners, and fewer CCS were married (16%) than among the SHS population (26%, P > 0.001). Older (OR = 1.14, P < 0.001) and female CCS (OR = 1.85, <0.001) were more likely to have life partners. CCS who had undergone radiotherapy, bone marrow transplants (global P Treatment = 0.018) or who had a CNS diagnosis (global P Diagnosis < 0.001) were less likely to have life partners. CONCLUSION: CCS are less likely to have life partners than their peers. Most CCS with a life partner were not married. Future research should focus on the effect of these disparities on the quality of life of CCS.

Older persons' perceptions of general practitioner or specialist primary care physicians : same point of view?

BACKGROUND: Identification of a Primary Care Physician (PCP) by older patients is considered as essential for the coordination of care, but the extent to which identified PCPs are general practitioners or specialists is unknown. This study described older patients' experiences with their PCP and tested the hypothesis of differences between patients who identify a specialist as their PCP (SP PCP) and those who turn to a general practitioner (GP PCP). METHODS: In 2012, a cross-sectional postal survey on care was conducted in the 68+ year old population of the canton of Vaud. Data was provided by 2,276 participants in the ongoing Lausanne cohort 65+ (Lc65+), a study of those born between 1934 and 1943, and by 998 persons from an additional sample drawn to include the population outside of Lausanne or born before 1934. RESULTS: Participants expressed favourable perceptions, at rates exceeding 75% for most items. However, only 38% to 51% responded positively for out-of-hours availability, easy access and at home visits, likelihood of prescribing expensive medication if needed, and doctors' awareness of over-the-counter drugs. 12.0% had an SP PCP, in 95.9% specialised in a discipline implying training in internal medicine. Bivariate and multivariate analyses did not result in significant differences between GP and SP PCPs regarding perceptions of accessibility/availability, doctor-patient relationship, information and continuity of care, prevention, spontaneous use of the emergency department or ambulatory care utilisation. CONCLUSIONS: Experiences of old patients were mostly positive despite some lack in reported hearing, memory testing, and colorectal cancer screening. We found no differences between GP and SP PCP groups.

Female residents experiencing medical errors in general internal medicine: a qualitative study.

BACKGROUND: Doctors, especially doctors-in-training such as residents, make errors. They have to face the consequences even though today's approach to errors emphasizes systemic factors. Doctors' individual characteristics play a role in how medical errors are experienced and dealt with. The role of gender has previously been examined in a few quantitative studies that have yielded conflicting results. In the present study, we sought to qualitatively explore the experience of female residents with respect to medical errors. In particular, we explored the coping mechanisms displayed after an error. This study took place in the internal medicine department of a Swiss university hospital. METHODS: Within a phenomenological framework, semi-structured interviews were conducted with eight female residents in general internal medicine. All interviews were audiotaped, fully transcribed, and thereafter analyzed. RESULTS: Seven main themes emerged from the interviews: (1) A perception that there is an insufficient culture of safety and error; (2) The perceived main causes of errors, which included fatigue, work overload, inadequate level of competences in relation to assigned tasks, and dysfunctional communication; (3) Negative feelings in response to errors, which included different forms of psychological distress; (4) Variable attitudes of the hierarchy toward residents involved in an error; (5) Talking about the error, as the core coping mechanism; (6) Defensive and constructive attitudes toward one's own errors; and (7) Gender-specific experiences in relation to errors. Such experiences consisted in (a) perceptions that male residents were more confident and therefore less affected by errors than their female counterparts and (b) perceptions that sexist attitudes among male supervisors can occur and worsen an already painful experience. CONCLUSIONS: This study offers an in-depth account of how female residents specifically experience and cope with medical errors. Our interviews with female residents convey the sense that gender possibly influences the experience with errors, including the kind of coping mechanisms displayed. However, we acknowledge that the lack of a direct comparison between female and male participants represents a limitation while aiming to explore the role of gender.

The role of career adaptability and work conditions on general and professional well-being.

This study, conducted with a representative sample of employed and unemployed adults living in Switzerland (N = 2002), focuses on work conditions (in terms of professional insecurity and job demands), career adaptability, and professional and general well-being. Analyses of covariance highlighted that both unemployed and employed participants with low job insecurity reported higher scores on career adaptability and several dimensions (notably on control) than employed participants with high job insecurity. Moreover, structural equation modeling for employed participants showed that, independent of work conditions, adaptability resources were positively associated both with general and professional well-being. As expected professional outcomes were strongly related to job strain and professional insecurity, emphasizing the central role of the work environment. Finally, career adaptability partially mediated the relationship between job strain and professional insecurity, and the outcome well-being.

Patients' prediction of extubation success.

The spontaneous breathing trial (SBT)-relying on objective criteria assessed by the clinician-is the major diagnostic tool to determine if patients can be successfully extubated. However, little is known regarding the patient's subjective perception of autonomous breathing. We performed a prospective observational study in 211 mechanically ventilated adult patients successfully completing a SBT. Patients were randomly assigned to be interviewed during this trial regarding their prediction of extubation success. We compared post-extubation outcomes in three patient groups: patients confident (confidents; n = 115) or not (non-confidents; n = 38) of their extubation success and patients not subjected to interview (control group; n = 58). Extubation success was more frequent in confidents than in non-confidents (90 vs. 45%; p < 0.001/positive likelihood ratio = 2.00) or in the control group (90 vs. 78%; p = 0.04). On the contrary, extubation failure was more common in non-confidents than in confidents (55 vs. 10%; p < 0.001/negative likelihood ratio = 0.19). Logistic regression analysis showed that extubation success was associated with patient's prediction [OR (95% CI): 9.2 (3.74-22.42) for confidents vs.non-confidents] as well as to age [0.72 (0.66-0.78) for age 75 vs. 65 and 1.31 (1.28-1.51) for age 55 vs. 65]. Our data suggest that at the end of a sustained SBT, extubation success might be correlated to the patients' subjective perception of autonomous breathing. The results of this study should be confirmed by a large multicenter trial.

Clinical and pharmacogenetic study on smoking and smoking cessation

Currently, smoking cessation represents one of the main strategies to reduce the incidence of tobacco-related diseases in the population. Smoking can also influence pharmacotherapy through several pharmacokinetic or pharmacodynamic interactions. Some of the most concerned drugs are those metabolized by the cytochrome P450 (CYP) 1A2 enzyme (e.g. caffeine, theophylline, clozapine, olanzapine, duloxetine), whose activity is induced by the polycyclic aromatic hydrocarbons found in tobacco smoke. This can result in a clinically significant decrease in the pharmacological effect of the drugs and the need of higher doses in smokers. Conversely, upon smoking cessation, toxic plasma levels of the drugs can be reached. The main objective of this thesis was to study the interindividual variability in CYP1A2 induction in a large cohort of smokers, by measuring CYP1A2 activity before smoking cessation and one month later in continuously abstinent subjects. For this purpose, a clinical study was conducted, including 194 smokers from the general population who wished to participate in a smoking cessation program and therefore received medical counseling and substitution therapy (nicotine or varenicline). An analytical method for the simultaneous quantification of nicotine, its metabolites and varenicline in plasma was developed and validated using ultra performance liquid chromatography coupled with tandem mass spectrometry. This method was used to confirm abstinence at different time points during the follow-up. Moreover, it was used to determine plasma levels of the smoking cessation drugs, to be used in the study of their pharmacogenetics, which was the secondary objective of this thesis. High interindividual variability in CYP1A2 induction by smoking was observed, ranging from no change to approximately 7 times decreased CYP1A2 activity after smoking cessation. Several clinical and genetic factors were investigated in an attempt to explain this variability. Firstly, a significant influence of CYP1A2*1F and *1D alleles, of contraceptive use and of the number of cigarettes smoked per day on CYP1A2 induced activity was observed, and of CYP1A2*1F and the use of contraceptives on the basal activity. But no influence of these factors was found on CYP1A2 inducibility. Given that known genetic polymorphisms in CYP1A2 gene were shown to explain only poorly the observed variations in activity, additional genetic factors were studied. SNPs in the CYP oxidoreductase (POR) gene were found to influence CYP1A2 basal activity, but not the induction. Finally, a pathway-based approach allowed to identify SNPs in genes coding for nuclear receptors (CAR, RXRa, VDR, PXR) and induction-mediating receptors (AhR), which significantly influenced CYP1A2 inducibility and basal activity (SNPs in the gene coding for CAR and RXRa). As secondary objective of the study, the pharmacogenetics of nicotine and varenicline is being investigated. Therefore, the nicotine metabolite ratio is used in the attempt to better explain nicotine dependence and the failure/success of quitting smoking. A population pharmacokinetic model is being developed for varenicline, integrating clinical and genetic factors (genes coding for its metabolizing enzymes and transporters), with the purpose of trying to predict efficacy and side effects. These findings suggest that the influence of smoking on pharmacotherapy could be better managed by including clinical and possibly in the future genetic factors, in the assessment of the adaptations needed when a person starts or stops smoking.  - L'arrêt du tabac représente une des principales stratégies pour diminuer l'incidence des maladies causées par celui-ci. Le tabagisme peut influencer la thérapie médicamenteuse par des interactions pharmacocinétiques ou pharmacodynamiques. Parmi les médicaments concernés, il y a ceux métabolisés par le cytochrome P450 (CYP) 1A2 (caféine, théophylline, clozapine, olanzapine, duloxétine, etc), dont l'activité enzymatique est induite par les hydrocarbures aromatiques polycycliques présents dans la fumée de cigarette. Ceci peut se traduire par une diminution de l'effet pharmacologique du traitement et la nécessité d'augmenter les doses d'entretien chez les fumeurs. Au contraire, à l'arrêt de la cigarette, les taux plasmatiques des médicaments peuvent devenir toxiques. L'objectif principal de cette thèse était d'étudier la variabilité interindividuelle dans l'induction du CYP1A2 dans une large cohorte de fumeurs, par la mesure de l'activité du CYP1A2 avant l'arrêt de la cigarette, ainsi qu'un mois après chez les sujets abstinents. Pour ce faire, une étude clinique a été conduite, incluant 194 fumeurs de la population générale dans un programme d'arrêt du tabac offrant des consultations spécifiques et un traitement pharmacologique (nicotine ou varénicline). Une méthode analytique pour la quantification simultanée de la nicotine, ses métabolites et la varénicline dans le plasma par chromatographie liquide couplée à la spectrométrie de masse en tandem à été développée et validée. Cette méthode a été utilisée pour confirmer l'abstinence pendant l'étude et déterminer les taux plasmatiques des médicaments, dans le but d'étudier leur pharmacogénétique. Une grande variabilité interindividuelle dans l'induction du CYP1A2 par la fumée a été observée, parfois sans changement et pouvant aller jusqu'à une diminution d'environ 7 fois l'activité du CYP1A2 après l'arrêt de la cigarette. Plusieurs facteurs cliniques et génétiques ont été étudiés pour essayer d'expliquer cette variabilité. Tout d'abord, on a observé une influence significative: des allèles CYP1A2*1F et *1D, des contraceptifs et du nombre de cigarettes fumées par jour sur l'activité induite du CYP1A2, ainsi que l'influence de l'allèle *1F et des contraceptifs sur l'activité basale. Cependant, aucune influence de ces facteurs n'a été démontrée sur l'inductibilité du CYP1A2. Étant donné que les polymorphismes génétiques du CYP1A2 apportent peu de renseignements sur la variabilité de son activité, des facteurs génétiques supplémentaires ont été étudiés. Des polymorphismes dans le gène POR (CYP oxidoreductase) ont été associés à l'activité basale du CYP1A2, mais pas à l'induction. Finalement, une approche basée sur la voie de signalisation du CYP1A2 a permis d'identifier des polymorphismes dans des gènes codant pour des récepteurs nucléaires (CAR, RXRa, VDR, PXR) et d'autres liés à l'induction (AhR) qui influencent significativement l'inductibilité et l'activité basale (les SNPs du CAR et RXRa). L'objectif secondaire de cette étude était d'investiguer la pharmacogénétique de la nicotine et de la varénicline. Le ratio métabolique de la nicotine est utilisé pour mieux expliquer la dépendance à la nicotine et le succès/échec de l'arrêt de la cigarette. Un modèle pharmacocinétique de population est en cours de développement pour la varénicline, intégrant des facteurs cliniques et génétiques (gènes codant pour ses enzymes de métabolisme et transporteurs), pour tenter de prédire son efficacité et ses effets secondaires. Les résultats de cette thèse suggèrent que l'influence du tabagisme sur la pharmacothérapie serait mieux gérée par l'inclusion des facteurs cliniques et peut-être, dans le futur, génétiques, dans l'évaluation des adaptations nécessaires lorsqu'une personne fume ou arrête de fumer.  - l'arrêt du tabac représente une des principales stratégies pour diminuer l'incidence des maladies causées par celui-ci dans la population. Le tabagisme peut influencer les traitements médicamenteux, soit en modifiant leur élimination par l'organisme, soit en agissant sur leur mode d'action. Parmi les médicaments les plus concernés, on retrouve par exemple: la caféine, la théophylline, la clozapine, l'olanzapine, la duloxétine, dont l'élimination est accélérée par la fumée de cigarette (induction enzymatique). Ceci peut se traduire par une diminution de l'effet du traitement et la nécessité d'en augmenter les doses chez les fumeurs. Au contraire, à l'arrêt de la cigarette, on observe un ralentissement de la fonction enzymatique, qui a pour conséquence une augmentation du taux de médicament dans le sang, pouvant devenir toxique. L'objectif principal de cette thèse était d'étudier comment cette induction par le tabac varie dans une population de fumeurs, par la mesure de l'activité de l'enzyme avant l'arrêt de la cigarette, ainsi qu'un mois après chez les sujets abstinents. Pour ce faire, une étude clinique a été conduite, incluant 194 fumeurs de la population générale dans un programme d'arrêt du tabac offrant des consultations spécifiques et un traitement médicamenteux (nicotine ou varénicline). Une méthode analytique a été mise au point pour mesurer la quantité de nicotine, de ses produits de dégradation et de la varénicline dans le sang des participants à l'étude. De plus, cette méthode a été utilisée pour confirmer l'abstinence pendant l'étude. Une grande variabilité interindividuelle a été observée dans l'induction de l'enzyme par la fumée; il en résulte aucun changement d'activité chez certains sujets après l'arrêt de la cigarette, alors que pour d'autres elle peut être diminuée jusqu'à 7 fois. Plusieurs facteurs cliniques et génétiques ont été étudiés pour essayer d'expliquer cette variabilité. Premièrement, une influence sur l'activité de l'enzyme a été observée pour les contraceptifs hormonaux et le nombre de cigarettes fumées par jour, ainsi que pour certaines variations génétiques dans le gène codant pour l'enzyme d'intérêt, mais il η y a pas eu d'influence sur l'induction. Par la suite, des variations génétiques dans d'autres gènes influençant le fonctionnement de l'enzyme ont été associées soit avec son activité, soit avec son induction par le tabac. Finalement, l'étude propose également d'investiguer si le métabolisme de la nicotine a une influence sur la dépendance, les symptômes de sevrage et le succès/échec de l'arrêt de la cigarette. Des variations génétiques dans les gènes du métabolisme de la varénicline sont également étudiées en lien avec les quantités de varénicline mesurées dans le sang ainsi que les effets du médicament. Ceci permettra peut-être de prédire son efficacité et ses effets secondaires. Les résultats de cette thèse suggèrent que l'influence du tabagisme sur la thérapie médicamenteuse serait mieux gérée en tenant compte des facteurs cliniques et peut-être, dans le futur, de la génétique dans l'adaptation des traitements, que la personne soit fumeuse ou en phase d'arrêt.

General Practitioners' willingness to pay for continuing medical education in a fee-for-service universal coverage health care system

Background: Sponsoring of physicians meetings by life science companies has led to reduced participation fees but might influence physician's prescription practices. A ban on such sponsoring may increase participation fees. We aimed to evaluate factors associated with physicians' willingness to pay for medical meetings, their position on the sponsoring of medical meetings and their opinion on alternative financing options. Methods: An anonymous web-based questionnaire was sent to 447 general practitioners in one state in Switzerland, identified through their affiliation to a medical association. The questionnaire evaluated physicians' willingness to pay for medical meetings, their perception of a bias in prescription practices induced by commercial support, their opinion on the introduction of a binding legislation and alternative financing options, their frequency of exchange with sales representatives and other relevant socioeconomic factors. We built a multivariate predictor logistic regression model to identify determinants of willingness to pay. Results: Of the 115 physicians who responded (response rate 26%), 48% were willing to pay more than what they currently pay for congresses, 79% disagreed that commercial support introduced a bias in their prescription practices and 61% disagreed that it introduced a bias in their colleagues' prescription practices. Based on the multivariate logistic regression, perception of a bias in peers prescription practices (OR=7.47, 95% CI 1.65-38.18) and group practice structure (OR=4.62, 95% CI 1.34-22.29) were significantly associated with an increase in willingness to pay. Two thirds (76%) of physicians did not support the introduction of a binding legislation and 53% were in favour of creating a general fund administered by an independent body. Conclusion: Our results suggest that almost half of physicians surveyed are willing to pay more than what they currently pay for congresses. Predictors of an increase in physicians' willingness to pay were perception of the influence of bias in peers prescription practices and group practice structure. Most responders did not agree that sponsoring introduced prescribing bias nor did they support the 2 introduction of a binding legislation prohibiting sponsoring but a majority did agree to an independent body that would centrally administer a general fund.

Investigation of Postmortem Gases: A Forensic Imaging and Analytical Chemistry Approach

Background: Distinguishing postmortem gas accumulations in the body due to natural decomposition and other phenomena such as gas embolism can prove a difficult task using purely Multi-Detector Computed Tomography (MDCT). The Radiological Alteration Index (RAI) was created with the intention to be able to identify bodies undergoing the putrefaction process based on the quantity of gas detected within the body. The flaw in this approach is the inability to absolutely determine putrefaction as the origin of gas volumes in cases of moderate alteration. The aim of the current study is to identify percentage compositions of O2, N2, CO2 and the presence of gases such as H2 and H2S within these sampling sites in order to resolve this complication. Materials and methods: All cases investigated in our University Center of Legal Medicine are undergoing a Post-Mortem Computed Tomography (PMCT)-scan before external examination or autopsy as a routine investigation. In the obtained images, areas of gas were characterized as 0, I, II or III based on the amount of gas present according to the RAI (1). The criteria for these characterizations were dependent of the site of gas, for example thoracic and abdominal cavities were graded as I (1 - 3cm gas), II (3 - 5cm gas) and III (>5cm gas). Cases showing gaseous sites with grade II or III were selected for this study. The sampling was performed under CT-guidance to target the regions to be punctured. Luer-lock PTFE syringes equipped with a three-way valve and needles were used to sample the gas directly (2). Gaseous samples were then analysed using gas chromatography coupled to a thermal conductivity detector (GC-TCD). The components present in the samples were expressed as a percentage of the overall gas present. Results: Up to now, we have investigated more than 40 cases using our standardized procedure for sampling and analysis of gas. O2, N2 and CO2 were present in most samples. The following distributions were found to correlate to gas origins of gas embolism/scuba diving accidents, trauma and putrefaction: ? Putrefaction → O2 = 1 - 5%; CO2 > 15%; N2 = 10 - 70%; H2 / H2S / CH4 variable presence ? Gas embolism/Scuba diving accidents → O2 and N2= varying percentages; CO2 > 20% ? Trauma → O2 = small percentage; CO2 < 15%; N2 > 65% H2 and H2S indicated levels of putrefaction along with methane which can also gauge environmental conditions or conditions of body storage/burial. Many cases showing large RAI values (advanced alteration) did reveal a radiological diagnosis which was in concordance with the interpretation of the gas composition. However, in certain cases (gas embolism, scuba divers) radiological interpretation was not possible and only chemical gas analysis was found to lead to the correct diagnosis, meaning that it provided complementary information to the radiological diagnosis. Conclusion: Investigation of postmortem gases is a useful tool to determine origin of gas generation which can aid the diagnosis of the cause of death. Levels of gas can provide information on stage of putrefaction and help to perform essential medico-legal diagnosis such as vital gas embolism.

DNA supercoiling and its role in DNA decatenation and unknotting.

Chromosomal and plasmid DNA molecules in bacterial cells are maintained under torsional tension and are therefore supercoiled. With the exception of extreme thermophiles, supercoiling has a negative sign, which means that the torsional tension diminishes the DNA helicity and facilitates strand separation. In consequence, negative supercoiling aids such processes as DNA replication or transcription that require global- or local-strand separation. In extreme thermophiles, DNA is positively supercoiled which protects it from thermal denaturation. While the role of DNA supercoiling connected to the control of DNA stability, is thoroughly researched and subject of many reviews, a less known role of DNA supercoiling emerges and consists of aiding DNA topoisomerases in DNA decatenation and unknotting. Although DNA catenanes are natural intermediates in the process of DNA replication of circular DNA molecules, it is necessary that they become very efficiently decatenated, as otherwise the segregation of freshly replicated DNA molecules would be blocked. DNA knots arise as by-products of topoisomerase-mediated intramolecular passages that are needed to facilitate general DNA metabolism, including DNA replication, transcription or recombination. The formed knots are, however, very harmful for cells if not removed efficiently. Here, we overview the role of DNA supercoiling in DNA unknotting and decatenation.

A general model to predict individual exposure to solar UV by using ambient irradiance data

Excessive exposure to solar ultraviolet (UV) is the main cause of skin cancer. Specific prevention should be further developed to target overexposed or highly vulnerable populations. A better characterisation of anatomical UV exposure patterns is however needed for specific prevention. To develop a regression model for predicting the UV exposure ratio (ER, ratio between the anatomical dose and the corresponding ground level dose) for each body site without requiring individual measurements. A 3D numeric model (SimUVEx) was used to compute ER for various body sites and postures. A multiple fractional polynomial regression analysis was performed to identify predictors of ER. The regression model used simulation data and its performance was tested on an independent data set. Two input variables were sufficient to explain ER: the cosine of the maximal daily solar zenith angle and the fraction of the sky visible from the body site. The regression model was in good agreement with the simulated data ER (R(2)=0.988). Relative errors up to +20% and -10% were found in daily doses predictions, whereas an average relative error of only 2.4% (-0.03% to 5.4%) was found in yearly dose predictions. The regression model predicts accurately ER and UV doses on the basis of readily available data such as global UV erythemal irradiance measured at ground surface stations or inferred from satellite information. It renders the development of exposure data on a wide temporal and geographical scale possible and opens broad perspectives for epidemiological studies and skin cancer prevention.

Genes associated with retinitis pigmentosa and allied diseases are frequently mutated in the general population.

BACKGROUND: Retinitis pigmentosa and other hereditary retinal degenerations (HRD) are rare genetic diseases leading to progressive blindness. Recessive HRD are caused by mutations in more than 100 different genes. Laws of population genetics predict that, on a purely theoretical ground, such a high number of genes should translate into an extremely elevated frequency of unaffected carriers of mutations. In this study we estimate the proportion of these individuals within the general population, via the analyses of data from whole-genome sequencing. METHODOLOGY/PRINCIPAL FINDINGS: We screened complete and high-quality genome sequences from 46 control individuals from various world populations for HRD mutations, using bioinformatic tools developed in-house. All mutations detected in silico were validated by Sanger sequencing. We identified clear-cut, null recessive HRD mutations in 10 out of the 46 unaffected individuals analyzed (∼22%). CONCLUSIONS/SIGNIFICANCE: Based on our data, approximately one in 4-5 individuals from the general population may be a carrier of null mutations that are responsible for HRD. This would be the highest mutation carrier frequency so far measured for a class of Mendelian disorders, especially considering that missenses and other forms of pathogenic changes were not included in our assessment. Among other things, our results indicate that the risk for a consanguineous couple of generating a child with a blinding disease is particularly high, compared to other genetic conditions.

A cohort-based analysis of the evolution of lifetime prevalence of recourse to prostitution by men in the general population of Switzerland, 1987-2000

Background: Despite their relevance to the prevention of sexually transmitted infections, there are few data on the frequency of recourse to prostitution in the male population in Switzerland. Using data gathered for the evaluation of the Swiss AIDS prevention strategy, we analysed net aggregate change and cohort-based change in lifetime prevalence of recourse to prostitution. Methods: Seven repeated cross-sectional telephone surveys of the general population aged 17-45 years (17-30 years only for the 1987 and 1988 surveys) were undertaken from 1987 to 2000 providing information on sexual behaviour including men's recourse to prostitution (total n¼9318). Age categories were: 17-20, 21-25, 26-30, 31-35, 36-40 and 41-45 years. Prevalence at 17-30 years was available in all surveys and prevalence at 41-45 was available for 1989-2000, though not for the same cohorts. Intra-cohort increase in prevalence over 10 years was analysed using truncated information for cohorts aged 21-25 and 26-30 years in 1987 and 1990. Population estimates were computed with 95% confidence intervals (CI). Results: No net change occurred in the 17-45 years male population prevalence between 1989 (17.6%, CI ¼ 15.4; 20.0) and 2000 (17.7%, CI ¼ 15.6; 20.0). The median starting prevalence of recourse to prostitution at age 17-20 was 4.8% (in 1989, CI ¼ 2.0; 9.7) and the range was from 1.8 (in 1994) to 10.4% (in 1990). The median ending prevalence at age 41-45 was 21.9% (in 1994, CI 16.7; 27.9) and the range was from 17.9 (in 2000) to 26.1% (in 1992). No clear trend was observed in either starting or ending prevalence. Intra-cohort evolution of the 1997 and 1990 cohorts was very similar. Conclusions: Based on available data, there was no net (aggregate) change in the prevalence of recourse to prostitution by males in Switzerland between 1989 and 2000. Within the time frame available, intra-cohort evolution was also very similar.

Mutations in the cdc10 start gene of Schizosaccharomyces pombe implicate the region of homology between cdc10 and SWI6 as important for p85cdc10 function.

The cdc10 gene of the fission yeast Schizosaccharomyces pombe is required for traverse of start and commitment to the mitotic cell division cycle rather than other fates. The product of the gene, p85cdc10, is a component of a factor that is thought to be involved in regulating the transcription of genes that are required for DNA synthesis. In order to define regions of the p85cdc10 protein that are important for its function a fine structure genetic map of the cdc10 gene was derived and the sequences of 13 cdc10ts mutants determined. The 13 mutants tested define eight alleles. Eleven of the mutants are located in the region that contains the two copies of the cdc10/SWI6 repeat motif, implicating it as important for p85cdc10 function.