Primary care at Swiss universities--current state and perspective.

BACKGROUND: There is increasing evidence that a strong primary care is a cornerstone of an efficient health care system. But Switzerland is facing a shortage of primary care physicians (PCPs). This pushed the Federal Council of Switzerland to introduce a multifaceted political programme to strengthen the position of primary care, including its academic role. The aim of this paper is to provide a comprehensive overview of the situation of academic primary care at the five Swiss universities by the end of year 2012. RESULTS: Although primary care teaching activities have a long tradition at the five Swiss universities with activities starting in the beginning of the 1980ies; the academic institutes of primary care were only established in recent years (2005 - 2009). Only one of them has an established chair. Human and financial resources vary substantially. At all universities a broad variety of courses and lectures are offered, including teaching in private primary care practices with 1331 PCPs involved. Regarding research, differences among the institutes are tremendous, mainly caused by entirely different human resources and skills. CONCLUSION: So far, the activities of the existing institutes at the Swiss Universities are mainly focused on teaching. However, for a complete academic institutionalization as well as an increased acceptance and attractiveness, more research activities are needed. In addition to an adequate basic funding of research positions, competitive research grants have to be created to establish a specialty-specific research culture.

Cerebellar transcranial direct current stimulation modulates verbal working memory.

BACKGROUND: Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. OBJECTIVE: We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. METHOD: We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. RESULTS: In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. CONCLUSION: Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions.

Carcinomes canalaires in situ: données anatomo-pathologiques actuelles [Ductal carcinoma in situ: current anatomo-pathologic data]

Ductal carcinoma in situ (DCIS), accounting for 15-25% of all breast cancers, is frequently diagnosed by mammographic examination. This heterogeneous disease requires a rigorous local treatment based, in about two-third of cases, on conservative surgery and radiotherapy. DCIS are currently classified on the basis of nuclear grade. Most lesions, and especially high nuclear grade DCIS, are limited to one quadrant. Micropapillary DCIS are likely to be of larger size/extent and thus a conservative approach is often difficult. A careful pathological examination of an oriented excisional biopsy is a pre-requisite for optimal therapy.

Current genetic data do not improve the prediction of type 2 diabetes mellitus: the CoLaus study.

CONTEXT: Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE: The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN: This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS: The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE: Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS: Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS: In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.

Pacemakers and magnetic resonance imaging: Current status and survey in Switzerland.

Electromagnetic fields arising from magnetic resonance imaging (MRI) can cause various clinically relevant functional disturbances in patients with cardiac pacemakers. Consequently, an implanted pacemaker is generally considered a contraindication for an MRI scan. With approximately 60 million MRI scans performed worldwide per year, MRI may be indicated for an estimated majority of pacemaker patients during the lifetime of their pacemakers. The availability of MR conditional pacemakers with CE labelling is of particular advantage since they allow the safe use of pacemakers in MRI. In this article the current state of knowledge on pacemakers and MR imaging is discussed. We present the results of a survey conducted among Swiss radiologists to assess current practice in patients with pacemakers.

The ghost of social environments past: dominance relationships include current interactions and experience carried over from previous groups.

Dominance hierarchies pervade animal societies. Within a static social environment, in which group size and composition are unchanged, an individual's hierarchy rank results from intrinsic (e.g. body size) and extrinsic (e.g. previous experiences) factors. Little is known, however, about how dominance relationships are formed and maintained when group size and composition are dynamic. Using a fusion-fission protocol, we fused groups of previously isolated shore crabs (Carcinus maenas) into larger groups, and then restored groups to their original size and composition. Pre-fusion hierarchies formed independently of individuals' sizes, and were maintained within a static group via winner/loser effects. Post-fusion hierarchies differed from pre-fusion ones; losing fights during fusion led to a decline in an individual's rank between pre- and post-fusion conditions, while spending time being aggressive during fusion led to an improvement in rank. In post-fusion tanks, larger individuals achieved better ranks than smaller individuals. In conclusion, dominance hierarchies in crabs represent a complex combination of intrinsic and extrinsic factors, in which experiences from previous groups can carry over to affect current competitive interactions.

A genome-wide significant linkage for severe depression on chromosome 3: the depression network study.

Objective: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. Method: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. Results: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. Conclusions: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.

Current standards and progress in understanding and treatment of GIST.

Gastrointestinal stromal tumours (GIST), despite being rare, pose a relevant medical problem from the viewpoint of diagnosis and management. GIST are fragile, liable to metastasize and often located in delicate structures. Surgical options, therefore, are limited. In the last decade an improved understanding of the molecular mechanisms of the disease has resulted in novel modes of treatment. The introduction of systemic tyrosine kinase inhibitor therapy with imatinib has significantly improved the outcome of the disease and prolonged the survival of GIST patients. For many patients the acute threat of a deadly cancer has been transformed into a manageable chronic condition. Drug safety, tolerability and compliance, subjects of concern in all long-term therapies, have proven to be acceptable for the tyrosine kinase inhibitor imatinib. The present paper provides a compact overview of the epidemiology, pathophysiology and morphology of GIST, with special reference to the underlying molecular biology. Relevant aspects of diagnosis, therapy and monitoring of the disease are reviewed with particular emphasis on the available clinical evidence and recent guidelines.

Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study.

Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10(-7)). These two SNPs were in high linkage disequilibrium (r(2) = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 x 10(-5)) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined.

Current cytogenetic map of the common shrew, Sorex araneus L.: localization of 7 genes and 4 microsatellites

Here we present information on the assignment of 7 genes, ACADVL, ADORA3, ATP7A, MTMR4, MYH2, HBB, TSPAN-3, and 4 common shrew microsatellites to chromosomes of the common shrew (Sorex araneus) and on the current status of its cytogenetic map. Comparative mapping data were used for the analysis of evolutionary chromosomal rearrangements in the common shrew genome.

High-frequency linkage of co-expressing T-DNA in transgenic Arabidopsis thaliana transformed by vacuum-infiltration of Agrobacterium tumefaciens

The efficiency of co-expression and linkage of distinct T-DNAs present in separate Agrobacterium tumefaciens was analysed in Arabidopsis thaliana transformed by the vacuum infiltration method. Co-expression was monitored by the synthesis of three bacterial proteins involved in the production of polyhydroxybutyrate (PHB) in the plastids. Out of 80 kanamycin-resistant transgenic plants analysed, 13 plants were co-transformed with the two distinct T-DNAs and produced PHB. Of those, 7 lines had a kanamycin-resistance segregation ratio consistent with the presence of a single functional insert. Genetic linkage between the distinct T-DNAs was demonstrated for all 13 PHB-producing lines, while physical linkage between the distinct T-DNAs was shown for 12 out of 13 lines. T-DNAs were frequently linked in an inverted orientation about the left borders. Transformation of A. thaliana by the co-infiltration of two A. tumefaciens containing distinct T-DNAs is, thus, an efficient approach for the integration and expression of several transgenes at a single locus. This approach will facilitate the creation and study of novel metabolic pathways requiring the expression of numerous transgenes.

Qualité des statistiques de causes de décès: problèmes actuels et perspectives. [Quality of statistics on causes of death: current problems and perspectives].

Statistics of causes of death remain an important source of epidemiological data for the evaluation of various medical and health problems. The improvement of analytical techniques and, above all, the transformation of demographic and morbid structures of populations have prompted researchers in the field to give more importance to the quality of death certificates. After describing the data collection system presently used in Switzerland, the paper discusses various indirect estimations of the quality of Swiss data and reviews the corresponding international literature.

3-d residual eddy current field characterisation: applied to diffusion weighted magnetic resonance imaging.

Clinical use of the Stejskal-Tanner diffusion weighted images is hampered by the geometric distortions that result from the large residual 3-D eddy current field induced. In this work, we aimed to predict, using linear response theory, the residual 3-D eddy current field required for geometric distortion correction based on phantom eddy current field measurements. The predicted 3-D eddy current field induced by the diffusion-weighting gradients was able to reduce the root mean square error of the residual eddy current field to ~1 Hz. The model's performance was tested on diffusion weighted images of four normal volunteers, following distortion correction, the quality of the Stejskal-Tanner diffusion-weighted images was found to have comparable quality to image registration based corrections (FSL) at low b-values. Unlike registration techniques the correction was not hindered by low SNR at high b-values, and results in improved image quality relative to FSL. Characterization of the 3-D eddy current field with linear response theory enables the prediction of the 3-D eddy current field required to correct eddy current induced geometric distortions for a wide range of clinical and high b-value protocols.

Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era.

Sexual dimorphism of the human mandible: demonstration by elliptical Fourier analysis.

A new quantitative approach of the mandibular sexual dimorphism, based on computer-aided image analysis and elliptical Fourier analysis of the mandibular outline in lateral view is presented. This method was applied to a series of 117 dentulous mandibles from 69 male and 48 female individuals native of Rhenish countries. Statistical discriminant analysis of the elliptical Fourier harmonics allowed the demonstration of a significant sexual dimorphism in 97.1% of males and 91.7% of females, i.e. in a higher proportion than in previous studies using classical metrical approaches. This original method opens interesting perspectives for increasing the accuracy of sex identification in current anthropological practice and in forensic procedures.