Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia.

Background Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including six GD families, we have mapped the disease gene on chromosome 9q34.2 and identified mutations in the A Disintegrin And Metalloproteinase with Thrombospondin repeats-like 2 gene (ADAMTSL2). Methods Following this study, we have collected the samples of 30 additional GD families, including 33 patients and identified ADAMTSL2 mutations in 14/33 patients, comprising 13 novel mutations. The absence of mutation in 19 patients prompted us to compare the two groups of GD patients, namely group 1, patients with ADAMTSL2 mutations (n=20, also including the 6 patients from our previous study), and group 2, patients without ADAMTSL2 mutations (n=19). Results The main discriminating features were facial dysmorphism and tip-toe walking, which were almost constantly observed in group 1. No differences were found concerning heart involvement, skin thickness, recurrent respiratory and ear infections, bronchopulmonary insufficiency, laryngo-tracheal stenosis, deafness, and radiographic features. Conclusions It is concluded that GD is a genetically heterogeneous condition. Ongoing studies will hopefully lead to the identification of another disease gene.

Incidence of invasive cervical cancer in the Swiss canton of Vaud, and a note on screening.

Age adjusted incidence rates (World standard) from invasive cervical cancer in the Swiss canton of Vaud decreased from 17.7/100,000 in 1968-70 to 9.9/100,000 in 1983-85. The decline was substantial in younger middle age, but no appreciable trend was observed in women over 70. This is consistent with available interview based information on the pattern of cervical screening in the Swiss population. Although there was no organised screening programme in Switzerland, over 80% of women aged 20-44 and 65% of those aged 45-64 reported one or more screening smears over the previous 3 years, compared to only 22% of women aged 65 or over. In the last calendar period, there was an apparent increase in the incidence of invasive cervical cancer (from 2.5 to 6.1/100,000) in women aged 25-29. Although based on small absolute numbers, this is in agreement with incidence and mortality data from other countries, and may therefore confirm a change in risk factor exposure in younger women.

Opportunistic screening actions for breast cancer performed by nurses working in primary health care

Abstract OBJECTIVE To identify opportunistic screening actions for breast cancer performed by nurses working in primary health care units in Ribeirão Preto, São Paulo. METHOD Cross-sectional study with 60 nurses from 28 units, who had been working for at least one year in the public municipal health care network. Data were collected between December 2013 and March 2014, by means of a questionnaire, using descriptive analysis and the software IBM SPSS version 20 and Microsoft Excel 2010. RESULTS The results showed that 71.7% of the participants questioned their female patients as for risk factors for breast cancer, mainly during nursing consultation; 70.0% oriented users about the age to perform clinical breast exam, whereas 30.0% did not due to lack of knowledge and time; 60.0% explained about the age to perform mammogram; 73.3% did not refer patients with suspicious breast exam results to the referral department, citing scheduling as the main obstacle to referral. Educational activities were not performed by 78.3% of participants. CONCLUSION Investment is needed in professional training and management of breast cancer screening.

Impact and cost of a 2-week community-based screening and awareness program for diabetes and cardiovascular risk factors in a Swiss canton.

BACKGROUND: Community-based diabetes screening programs can help sensitize the population and identify new cases. However, the impact of such programs is rarely assessed in high-income countries, where concurrent health information and screening opportunities are common place. INTERVENTION AND METHODS: A 2-week screening and awareness campaign was organized as part of a new diabetes program in the canton of Vaud (population of 697,000) in Switzerland. Screening was performed without appointment in 190 out of 244 pharmacies in the canton at the subsidized cost of 10 Swiss Francs per participant. Screening included questions on risk behaviors, measurement of body mass index, blood pressure, blood cholesterol, random blood glucose (RBG), and A1c if RBG was >/=7.0 mmol/L. A mass media campaign promoting physical activity and a healthy diet was channeled through several media, eg, 165 spots on radio, billboards in 250 public places, flyers in 360 public transport vehicles, and a dozen articles in several newspapers. A telephone survey in a representative sample of the population of the canton was performed after the campaign to evaluate the program. RESULTS: A total of 4222 participants (0.76% of all persons aged >/=18 years) underwent the screening program (median age: 53 years, 63% females). Among participants not treated for diabetes, 3.7% had RBG >/= 7.8 mmol/L and 1.8% had both RBG >/= 7.0 mmol/L and A1c >/= 6.5. Untreated blood pressure >/=140/90 mmHg and/or untreated cholesterol >/=5.2 mmol/L were found in 50.5% of participants. One or several treated or untreated modifiable risk factors were found in 78% of participants. The telephone survey showed that 53% of all adults in the canton were sensitized by the campaign. Excluding fees paid by the participants, the program incurred a cost of CHF 330,600. CONCLUSION: A community-based screening program had low efficiency for detecting new cases of diabetes, but it identified large numbers of persons with elevated other cardiovascular risk factors. Our findings suggest the convenience of A1c for mass screening of diabetes, the usefulness of extending diabetes screening to other cardiovascular risk factors, and the importance of a robust background communication campaign.

Interbank comptetition with costly screening

We analyse credit market equilibrium when banks screen loan applicants. When banks have a convex cost function of screening, a pure strategy equilibrium exists where banks optimally set interest rates at the same level as their competitors. This result complements Broecker s (1990) analysis, where he demonstrates that no pure strategy equilibrium exists when banks have zero screening costs. In our set up we show that interest rate on loansare largely independent of marginal costs, a feature consistent with the extant empirical evidence. In equilibrium, banks make positive profits in our model in spite of the threat of entry by inactive banks. Moreover, an increase in the number of active banks increases credit risk and so does not improve credit market effciency: this point has important regulatory implications. Finally, we extend our analysis to the case where banks havediffering screening abilities.

Weighted metric multidimensional scaling

This paper establishes a general framework for metric scaling of any distance measure between individuals based on a rectangular individuals-by-variables data matrix. The method allows visualization of both individuals and variables as well as preserving all the good properties of principal axis methods such as principal components and correspondence analysis, based on the singular-value decomposition, including the decomposition of variance into components along principal axes which provide the numerical diagnostics known as contributions. The idea is inspired from the chi-square distance in correspondence analysis which weights each coordinate by an amount calculated from the margins of the data table. In weighted metric multidimensional scaling (WMDS) we allow these weights to be unknown parameters which are estimated from the data to maximize the fit to the original distances. Once this extra weight-estimation step is accomplished, the procedure follows the classical path in decomposing a matrix and displaying its rows and columns in biplots.

Label-free cytotoxicity screening assay by digital holographic microscopy

Abstract We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screening compatible application, we automatized a digital holographic microscope for image acquisition of cells using commercially available 96-well plates. Data generated through both label-free DHM imaging and fluorescence-based methods were in good agreement for cell viability identification and a Z'-factor close to 0.9 was determined, validating the robustness of DHM assay for phenotypic screening. Further, an excellent correlation was obtained between experimental cytotoxicity dose-response curves and known IC values for different toxic compounds. For comparable results, DHM has the major advantages of being label free and close to an order of magnitude faster than automated standard fluorescence microscopy.

L'assurance de qualité en dépistage organise du cancer du sein [Quality assurance in organized screening of breast cancer]

Quality assurance is an essential process which should be applied for any organised breast cancer screening program since mammography it the only test available for an early diagnosis. It should also assess the quality of diagnostic and treatment processes in order to ascertain that the quality of the screening program would not be altered by the procedures which take place after the screening. Quality assurance must be applied to each component of the screening process: equipment, radiographers (technicians) as well as radiologists. It is a multidisciplinary approach following a well defined protocol, which should be supervised by a coordination unit, the Breast Cancer Screening Foundation in Canton of Vaud. Performances of the Vaud program show clearly at what extend multiple reading method improves the quality of screening. It seems that there is no inconvenient to involve radiologists who wish to participate without any selection to the reading process provided that there is in place a team of 2nd and 3rd readers who benefit of an appropriate training and experience.

Use of a combined ex vivo/in vivo population approach for screening of human genes involved in the human immunodeficiency virus type 1 life cycle for variants influencing disease progression.

Humans differ substantially with respect to susceptibility to human immunodeficiency virus type 1 (HIV-1). We evaluated variants of nine host genes participating in the viral life cycle for their role in modulating HIV-1 infection. Alleles were assessed ex vivo for their impact on viral replication in purified CD4 T cells from healthy blood donors (n = 128). Thereafter, candidate alleles were assessed in vivo in a cohort of HIV-1-infected individuals (n = 851) not receiving potent antiretroviral therapy. As a benchmark test, we tested 12 previously reported host genetic variants influencing HIV-1 infection as well as single nucleotide polymorphisms in the nine candidate genes. This led to the proposition of three alleles of PML, TSG101, and PPIA as potentially associated with differences in progression of HIV-1 disease. In a model considering the combined effects of new and previously reported gene variants, we estimated that their effect might be responsible for lengthening or shortening by up to 2.8 years the period from 500 CD4 T cells/mul to <200 CD4 T cells/mul.

Prevalence of positive tuberculosis skin tests during 5 years of screening in a Swiss remand prison

BACKGROUND: Tuberculosis (TB) screening in prisons is recommended, but the appropriate methods remain controversial. Studies evaluating screening in remand prisons arc scarce. METHOD: Between 1997 and 2001, voluntary screening based on the tuberculin skin test (TST) was offered to all prisoners on entry into the largest remand prison in Switzerland. Prisoners with positive results underwent chest X-rays. We analysed this information collected in an anonymous database. RESULTS: A total of 4890 prisoners entered the prison and were eligible for screening; 3779 (77.3%) had TST performed on average 9 days after arrival: 46.9% were positive (induration >= 10 mm). Positive TST rates were similar over the 5 years. Women were more likely to have a negative TST (60.4%) than men (47.7%; P < 0.001, Pearson's chi(2) 16.5). Positive TSTs varied according to the prisoner's country of origin (64% for sub-Saharan Africa, 57% for Eastern Europe, 56% for North Africa, 51% for Asia and 34% for North and West Europe). CONCLUSION: The percentage of TST-positive subjects was high, and most did not receive preventive treatment for latent TB. The usefulness of systematic TST for all prisoners on entry is limited, as diagnosis of TB disease usually remains the priority in prisons. Keywords

Sequential screening

We present a model of price discrimination where a monopolistfaces a consumer who is privately informed about thedistribution of his valuation for an indivisible unit ofgood but has yet to learn privately the actual valuation.The monopolist sequentially screens the consumer with amenu of contracts:the consumer self-selects once by choosing a contract andthen self-selects again when he learns the actual valuation. A deterministic sequential mechanism is a menu of refundcontracts, each consisting of an advance payment and a refundamount in case of no consumption, but sequential mechanismsmay involve randomization.We characterize the optimal sequential mechanism when someconsumer types are more eager in the sense of first-orderstochastic dominance, and when some types face greatervaluation uncertainty in the sense of mean-preserving-spread.We show that it can be optimal to subsidize consumer typeswith smaller valuation uncertainty (through low refund, as inairplane ticket pricing) in order to reduce the rent to thosewith greater uncertainty. The size of distortion depends bothon the type distribution and on how informative the consumer'sinitial private knowledge is about his valuation, but noton how much he initially knows about the valuation per se.

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Enseignement de recommandations pour la pratique: la prévention et le dépistage [Teaching practice recommendations: prevention and screening].

The aim of this article is to provide guidance to family doctors on how to tutor students about effective screening and primary prevention. Family doctors know their patients and adapt national and international guidelines to their specific context, risk profile, sex and age as well as to the prevalence of the disorders under consideration. Three cases are presented to illustrate guideline use according to the level of evidence (for a 19-year-old man, a 60-year-old woman, and an 80-year-old man). A particular strength of family medicine is that doctors see their patients over the years. Thus they can progressively go through the various prevention strategies, screening, counselling and immunisation, accompanying their patients with precious advice for their health throughout their lifetime.