Establishment of a Representative Practice-based Research Network (PBRN) for the Monitoring of Primary Care in Switzerland.

Data are urgently needed to better understand processes of care in Swiss primary care (PC). A total of 2027 PC physicians, stratified by canton, were invited to participate in the Swiss Primary care Active Monitoring network, of whom 200 accepted to join. There were no significant differences between participants and a random sample drawn from the same physician databases based on sex, year of obtaining medical school diploma, or location. The Swiss Primary care Active Monitoring network represents the first large-scale, nationally representative practice-based research network in Switzerland and will provide a unique opportunity to better understand the functioning of Swiss PC.

Primary care in Switzerland: evolution of physicians' profile and activities in twenty years (1993-2012).

BACKGROUND: According to the Organization for Economic Cooperation and Development, the Swiss healthcare system is one of the most effective in the world. Yet, as other occidental countries, it has to face the increase of chronic diseases frequency and its resulting cost, particularly for primary care (PC). However very few consistent data are available to describe PC features and its evolution over time. The aim of this study is to describe the evolution of the Swiss PC physicians' (PCPs) profile and activities between 1993 and 2012. METHODS: The date come from two independent European surveys carried out in Switzerland respectively in 1993 and 2012. Both surveys were cross-sectional ones and based on representative samples of 200 PCPs, interviewed by questionnaire. RESULTS: In 20 years, PCPs became older (median age 46 vs 56, p < 0.001) and more feminized (7 % vs 22 %, p < 0.001). Nowadays, they more often work in group practices (28 % vs 52 % in 2012, p < 0.001) and are more involved in other paid activities (28 % vs 66 % in 2012, p < 0.001). All the PCPs have a computer in 2012 (78 % in 1993, p < 0.001) and it is mostly used for keeping records of consultations (47 %). The number of daily face-to-face contacts with patients decreased from 31 to 24 but the average length rose from 15 to 20 min (p < 0.001). PCPs provide fewer pediatric and gynecological services but their activity remains globally unchanged in other domains. The frequency of meetings with other disciplines decreased significantly (e.g. once/month face-to-face meets with ambulatory specialists: 78 % vs 23 % in 2012, p < 0.001). The involvement of PCPs in follow-up and treatment of chronic disease globally little differed. In 2012, 8.5 % of the PCPs never performed any chirurgical acts (vs 0 % in 1993, p < 0.001). CONCLUSION: This study showed a substantial evolution of Swiss PC over the last twenty years in terms of socio-demographic, organizational and service provided. The main changes include: feminization and ageing, lower diversity in services provided, fewer but longer consultations. These changes may have important implications for patients' management and will need to be considered for health planning purposes.

Reaaliaikaisen tiedonsiirtolinkin muodostaminen prosessisäädön simulointi- ja valvomo-ohjelmiston välille

Teollisuusautomaatiossa käytetään varta vasten automaatiosovelluksiin tarkoitettuja tietokoneita eli ohjelmoitavia logiikoita (PLC, Programmable Logic Control). Ohjelmoitavan logiikan ja käyttäjän välillä on hyvin useasti jonkin asteinen käyttöliittymä (HMI, Human-Machine Interface). Käyttöliittymä voidaan toteuttaa logiikkaan liitettävien näyttöpäätteiden tai PC-pohjaisten valvomo-ohjelmien avulla. Käyttöliittymän kautta käyttäjä voi valvoa ja ohjata automaatiojärjestelmää. Tämän kandidaatintyön aiheena on reaaliajassa toimivan tiedonsiirtolinkin luominen prosessisäädön simulointiohjelmiston ja valvomo-ohjelmiston välille. Prosessiasäätöä simuloidaan MATLAB:in Simulink-ohjelmistolla ja käyttöliittymä luodaan InTouch valvomo-ohjelmistolla. Simuloitavana prosessina toimii nelitankkiprosessi, jossa kahden tankin pinnankorkeutta säädetään kahdella pumpulla. Prosessista tekee erittäin mielenkiintoisen se, että prosessilla on kolmitieventtiilien asennoista riippuen kaksi eri toimintapistettä: minimivaiheinen ja ei-minimivaiheinen. Myös tankkien ristiinkytköksien johdosta prosessi on normaalia tankkiprosessia mielenkiintoisempi. Tiedonsiirtolinkin muodostaminen prosessisäädön simuloinnin sekä valvomo-ohjelmiston välille mahdollistaa lukuisia erilaisia käyttötarkoituksia. Varsinkin opetuskäytössä tämä on erittäin käyttökelpoinen, koska se ei vaadi todellisen prosessin eikä laitteistojen läsnäoloa. Sen avulla voidaan opettaa valvomo-ohjelmien luomista sekä niiden käyttöä. Myös prosessisäätöä voidaan opettaa erittäin havainnollisesti.

Optical spectroscopy of microquasar candidates at low Galactic latitudes

We report optical spectroscopic observations of a sample of 6 low-galactic latitude microquasar candidates selected by cross-identification of X-ray and radio point source catalogs for |b|<5 degrees. Two objects resulted to be of clear extragalactic origin, as an obvious cosmologic redshift has been measured from their emission lines. For the rest, none exhibits a clear stellar-like spectrum as would be expected for genuine Galactic microquasars. Their featureless spectra are consistent with being extragalactic in origin although two of them could be also highly reddened stars. The apparent non-confirmation of our candidates suggests that the population of persistent microquasar systems in the Galaxy is more rare than previously believed. If none of them is galactic, the upper limit to the space density of new Cygnus X-3-like microquasars within 15 kpc would be 1.1\times10^{-12} per cubic pc. A similar upper limit for new LS 5039-like systems within 4 kpc is estimated to be 5.6\times10^{-11} per cubic pc.

Assessing Recent Selection and Functionality at Long Noncoding RNA Loci in the Mouse Genome.

Long noncoding RNAs (lncRNAs) are one of the most intensively studied groups of noncoding elements. Debate continues over what proportion of lncRNAs are functional or merely represent transcriptional noise. Although characterization of individual lncRNAs has identified approximately 200 functional loci across the Eukarya, general surveys have found only modest or no evidence of long-term evolutionary conservation. Although this lack of conservation suggests that most lncRNAs are nonfunctional, the possibility remains that some represent recent evolutionary innovations. We examine recent selection pressures acting on lncRNAs in mouse populations. We compare patterns of within-species nucleotide variation at approximately 10,000 lncRNA loci in a cohort of the wild house mouse, Mus musculus castaneus, with between-species nucleotide divergence from the rat (Rattus norvegicus). Loci under selective constraint are expected to show reduced nucleotide diversity and divergence. We find limited evidence of sequence conservation compared with putatively neutrally evolving ancestral repeats (ARs). Comparisons of sequence diversity and divergence between ARs, protein-coding (PC) exons and lncRNAs, and the associated flanking regions, show weak, but significantly lower levels of sequence diversity and divergence at lncRNAs compared with ARs. lncRNAs conserved deep in the vertebrate phylogeny show lower within-species sequence diversity than lncRNAs in general. A set of 74 functionally characterized lncRNAs show levels of diversity and divergence comparable to PC exons, suggesting that these lncRNAs are under substantial selective constraints. Our results suggest that, in mouse populations, most lncRNA loci evolve at rates similar to ARs, whereas older lncRNAs tend to show signals of selection similar to PC genes.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

The Besançon Galaxy Model renewed. I. Constraints on the Galactic thin disc evolution from Tycho data

Context. The understanding of Galaxy evolution can be facilitated by the use of population synthesis models, which allow to test hypotheses on the star formation history, star evolution, as well as chemical and dynamical evolution of the Galaxy. Aims. The new version of the Besanc¸on Galaxy Model (hereafter BGM) aims to provide a more flexible and powerful tool to investigate the Initial Mass Function (IMF) and Star Formation Rate (SFR) of the Galactic disc. Methods. We present a new strategy for the generation of thin disc stars which assumes the IMF, SFR and evolutionary tracks as free parameters. We have updated most of the ingredients for the star count production and, for the first time, binary stars are generated in a consistent way. We keep in this new scheme the local dynamical self-consistency as in Bienayme et al (1987). We then compare simulations from the new model with Tycho-2 data and the local luminosity function, as a first test to verify and constrain the new ingredients. The effects of changing thirteen different ingredients of the model are systematically studied. Results. For the first time, a full sky comparison is performed between BGM and data. This strategy allows to constrain the IMF slope at high masses which is found to be close to 3.0, excluding a shallower slope such as Salpeter"s one. The SFR is found decreasing whatever IMF is assumed. The model is compatible with a local dark matter density of 0.011 M pc−3 implying that there is no compelling evidence for significant amount of dark matter in the disc. While the model is fitted to Tycho2 data, a magnitude limited sample with V<11, we check that it is still consistent with fainter stars. Conclusions. The new model constitutes a new basis for further comparisons with large scale surveys and is being prepared to become a powerful tool for the analysis of the Gaia mission data.

Modulation de la douleur neuropathique par l'utilisation d'un vecteur viral adéno-associé recombinant et ARN interférent

Une lésion nerveuse périphérique est susceptible d'engendrer une douleur neuropathique caractérisée par des changements d'expression génique dans les neurones nociceptifs des ganglions spinaux. Parmi ces modifications, on note une augmentation transcriptionnelle du gène codant pour la guanosine triphosphate cyclohydrolase 1 (GCH1) considérée comme modulateur clé des douleurs neuropathiques périphériques1. La surexpression de la GCH1 induit alors une hausse de la concentration de la tétrahydrobiopterin (BH4), un cofacteur essentiel pour la production de catécholamines, de sérotonine et d'oxide nitrique dans les ganglions spinaux. La surexpression de ce cofacteur induit la production de ces neurotransmetteurs et contribue à l'augmentation de la sensibilité douloureuse. Dans ce travail, j'ai modulé l'expression de GCH1 par l'utilisation d'un vecteur viral adéno-associé. Tout d'abord, j'ai testé in vitro dans des cellules PC12 différentes molécules d'ARN interfèrent permettant la régulation négative de GCH1. Les cellules PC 12 contiennent constitutionnellement la GCH1 et sont donc intéressantes afin de tester et sélectionner un plasmide permettant une régulation négative efficace de cette molécule in vitro. Cela m'a permis de choisir après sélection de cellules par FACS et quantification protéique par Western blot les meilleurs sh-ARN à utiliser tant pour la régulation négative de GCH1 que pour le vecteur contrôle. J'ai ensuite co- transfecté ces plasmides avec le plasmide pDF6 dans des cellules HEK293T pour la production de mon vecteur viral (rAAV2/6) permettant la régulation négative de la GCH1 ainsi que de mon vecteur contrôle. Après avoir étudié deux voies d'injection chez le rat (dans le nerf sciatique et en intrathécal), j'ai retenu la voie intrathécale comme ayant le meilleur taux de transduction de mon vecteur viral au niveau des ganglions spinaux. Utiliser cette voie d'injection pour mon vecteur permet de cibler plus particulièrement les neurones nociceptifs des ganglions spinaux. J'ai ensuite étudié la modulation de la GCH1 et sa répercussion sur le développement et le maintien des douleurs neuropathiques dans le modèle animal « spared nerve injury » (SNI). Je n'ai pas obtenu de diminution de douleur ni au niveau comportemental ni au niveau moléculaire chez le rat. Ayant répété l'expérience chez la souris, j'ai obtenu une diminution significative de l'expression de la GCH1 au niveau de l'ARN messager. Je n'ai pas étudié l'efficacité de mon vecteur in vivo chez la souris car un autre groupe m'a devancé dans cette expérience et a publié une étude similaire montrant une régulation négative et efficace de la GCH1 sur les symptômes de douleur neuropathique. Mes résultats, associés à cette publication, démontrent la validité de mon hypothèse de départ et ouvrent de nouvelles perspectives thérapeutiques en prenant comme cible la production de BH4.

Alterações parenquimatosas na trombose venosa cerebral: aspectos da ressonância magnética e da angiorressonância

OBJETIVO: Determinar a freqüência e localização das alterações parenquimatosas da trombose venosa cerebral nos exames de ressonância magnética e de angiorressonância, bem como a correlação com o território e a drenagem venosa comprometida. MATERIAIS E MÉTODOS: Foram analisados exames de 21 pacientes realizados entre 1996 e 2004, com diagnóstico clínico e radiológico de trombose venosa cerebral em exames de ressonância magnética e de angiorressonância nas seqüências 2D PC, 3D PC e 3D TOF com contraste paramagnético. Análise estatística foi realizada com o teste do qui quadrado. Quatro pacientes tinham exames de controle e três realizaram angiografia por subtração digital. RESULTADOS: Dos 21 pacientes, 18 eram mulheres, todos com idade entre três e 82 anos (média de 40 anos e mediana de 36 anos). Os principais fatores etiológicos foram infecção, uso de contraceptivos orais, reposição hormonal e colagenoses. Predominaram os sintomas de déficit focal, cefaléia, alteração do nível de consciência e convulsões. Por freqüência, as manifestações parenquimatosas foram: edema/infarto de distribuição cortical e/ou subcortical, congestão venosa e circulação colateral, realce meníngeo e infarto ou edema dos tálamos e núcleos da base. Os principais seios comprometidos foram o sagital superior, o transverso esquerdo, o sigmóide esquerdo e o seio reto, sendo incomum o acometimento dos seios cavernosos e de veias corticais. CONCLUSÃO: A trombose venosa cerebral é causa incomum de acidente vascular encefálico, com prognóstico favorável pelo caráter reversível das lesões. Seu diagnóstico depende fundamentalmente da capacidade do radiologista reconhecer suas formas de apresentação, principalmente nos casos em que ele é sugerido pelas alterações parenquimatosas e não necessariamente pela visualização do trombo. A precisão e a rapidez no diagnóstico permitem o pronto tratamento, reduzindo a morbi-mortalidade da doença.

3,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptors

Nicotine (NIC), the main psychostimulant compound of smoked tobacco, exerts its effects through activation of central nicotinic acetylcholine receptors (nAChR), which become up-regulated after chronic administration. Recent work has demonstrated that the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has affinity for nAChR and also induces up-regulation of nAChR in PC 12 cells. Tobacco and MDMA are often consumed together. In the present work we studied the in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or combined with a chronic schedule of NIC, on the density of nAChR and on serotonin reuptake transporters. MDMA induced significant decreases in [3H]paroxetine binding in the cortex and hippocampus measured 24 h after the last dose and these decreases were not modified by the association with NIC. In the prefrontal cortex, NIC and MDMA each induced significant increases in [3H]epibatidine binding (29.5 and 34.6%, respectively) with respect to saline-treated rats, and these increases were significantly potentiated (up to 72.1%) when the two drugs were associated. Also in this area, [3H]methyllycaconitine binding was increased a 42.1% with NIC + MDMA but not when they were given alone. In the hippocampus, MDMA potentiated the a7 regulatory effects of NIC (raising a 25.5% increase to 52.5%) but alone was devoid of effect. MDMA had no effect on heteromeric nAChR in striatum and a coronal section of the midbrain containing superior colliculi, geniculate nuclei, substantia nigra and ventral tegmental area. Specific immunoprecipitation of solubilised receptors suggests that the up-regulated heteromeric nAChRs contain a4 and b2 subunits. Western blots with specific a4 and a7 antibodies showed no significant differences between the groups, indicating that, as reported for nicotine, up-regulation caused by MDMA is due to post-translational events rather than increased receptor synthesis.

Subthalamic (STN) Deep Brain Stimulation (DBS) in Parkinson's Disease (PD): Correlation Between the Location of the Stimulated Contacts and the Clinical Effects in 14 Patients

Objectives: To correlate the chronic stimulated electrode position on postoperative MRI with the clinical response obtained in PD patients. Material and Method: We retrospectively reviewed 14 consecutive parkinsonian patients who were selected for STN-DBS surgery. Coordinates were determined on an IR T2 MRI coronal section per pendicular to AC-PC plane 3 mm posterior to midcommissural point (MCP) and 12 mm lateral to the midline the inferior aspect of subthalamic region. A CRW stereotactic frame was used for the surgical procedure. A 3D IR T2 MRI was performed postoperatively to determine the location of the stimulated contact in each patient. The clinical results were assessed independently by the neurological team. Results: All but 2 patients had monopolar stimulation. The mean coordinates of the stimulated contacts were: AP ^ ÿ4:23G1:4, Lat ^ 1:12G0:15, Vert ^ ÿ4:1 G2:7 to the MCP. With a mean follow-up of 8 months, all stimulated patients had a significant clinical improvement (preop/postop «ON» UPDRS: 25:8G7:0= 23:3 G8:6; preop/postop «OFF» UPDRS: 50:2G11:4=26:0 G7:8), 60% of them without any antiparkinsonian drug. Conclusion: According to the stereotactic atlas of Schaltenbrand and Warren and the 3D shape of the STN, our results show that our targetting is accurate and almost all the stimulated contacts are comprised in the STN volume. This indicates that MRI is a safe, precise and reproducible procedure for targetting the STN. The location of the stimulated contact within the STN volume is a good predictor of the clinical results.

Pots&Plants Aplicació de Realitat Augmentada

Joc de Realitat Augmentada on l’usuari haurà de complir petits reptes interactuant amb els elements virtuals de l’escena. Aquests elements es presentaran fent us de marcadors. El projecte és un joc on l’usuari ha de cuidar unes plantes. Per a poder fer aquesta feina el jugador realitzarà 3 tipus de reptes. Aquests reptes són petits jocs, és a dir, que hi ha tres tipus de “mini-jocs” dintre de la Aplicació. Degut a que cada jugador té preferències diferents, aquesta divisió́ de jocs permet accedir a un major nombre d’usuaris. Pel seu desenvolupament s'ha fet un recull d’informació i evolució històrica de la Realitat Augmentada. S'han agafant referents de jocs similars en el mercat: PC, Apps i videoconsoles com a base d’inspiració per a la creació de la historia del joc. I finalment una recollida de requeriments tècnics per al desenvolupament tecnològic a nivell de programació i disseny. Amb tota aquesta informació i tenint com a medis de desenvolupament Blender, Unity + Vuforia s'ha complert la implementació del joc.

"Hit the primary": A paradigm shift in the treatment of metastatic prostate cancer?

Patients with metastatic prostate cancer (PC) represent a heterogeneous group with survival rates varying between 13 and 75 months. The current standard treatment in this setting is hormonal therapy, with or without docetaxel-based chemotherapy. In the era of individualized medicine, however, maximizing treatment options, especially in long-term surviving patients with limited disease burden, is of capital importance. Emerging data, mainly from retrospective surgical series, show survival benefits in men diagnosed with metastatic PC following definitive therapy for the prostate. Whether the irradiation of primary tumor in a metastatic disease might improve the therapeutic ratio in association with systemic treatments remains investigational. In this scenario, modern radiation therapy (RT) can play a significant role owing to its intrinsic capability to act as a more general immune response modifier, as well as to the potentially better toxicity profile compared to surgery. Preclinical data, clinical experience, and challenges in local treatment in de novo metastatic PC are reviewed and discussed.

Implementació d’un sistema SCADA a la cèl·lula de fabricació flexible MPS+2000C

L’Escola Politècnica Superior de la Universitat de Vic disposa d’una cèl·lula de fabricació flexible del fabricant Festo, que simula un procés d’emmagatzematge automàtic, aquesta cèl·lula esta composta per quatre estacions de muntatge diferenciades i independents, l’estació palets, l’estació plaques, l’estació magatzem intermedi i l’estació transport. Cada una d’aquestes estacions està formada per sensors i actuadors elèctrics i pneumàtics del fabricant Festo que van connectats a un PLC SIEMENS S7-300.Els quatre PLC’s (un per cada estació) estan connectats entre ells mitjançant el bus de comunicacions industrials Profibus. L’objectiu d’aquest treball consisteix en l’adaptació de la programació dels PLC’s i la realització d’un SCADA per tal de controlar el funcionament del conjunt de la cèl·lula de fabricació a través del software Vijeo Citect, d’aquesta manera es coneixerà el funcionament de la cèl·lula i permetrà treure’n rendiment per la docència. Aquest projecte ha estat realitzat en quatre fases principals. 1. Estudi i coneixement de les estacions, en aquesta fase s’han estudiat els manuals de funcionament de les estacions i s’han interpretat els codis de programació dels seus PLCs, amb l’objectiu de conèixer bé el programa per tal de interaccionar-hi més endavant amb el sistema SCADA 2. Disseny i programació del sistema SCADA, en aquesta fase s’ha realitzat tot el disseny gràfic de les pantalles de la interfície SCADA així com la programació dels objectes, la connexió amb els PLCs i la base de dades. 3. Posada en marxa del sistema complert, quan es coneixia abastament el funcionament de les estacions i el sistema SCADA estava completat s’ha fet la posada en marxa del conjunt i s’ha comprovat el correcte funcionament i interacció dels sistemes. 4. Realització de la memòria del projecte, en aquesta ultima fase s’ha realitzat la memòria del projecte on s’expliquen les característiques i funcionament de totes les estacions i del sistema SCADA. La conclusió més rellevant obtinguda en aquest treball, és la clara visualització de la potència i simplicitat que han aportat els sistemes SCADA al món de l’automatització, anys enrere per la supervisió de l’estat d’un sistema automatitzat era necessari disposar d’un gran espai amb grans panells de control formats per una gran quantitat de pilots lluminosos, potenciòmetres, interruptors, polsadors, displays i sobretot un voluminós i complexa cablejat, gràcies als sistemes SCADA avui en dia tot això pot quedar reduït a un PC o terminal tàctil, amb pantalles gràfiques clares i una gran quantitat d’opcions de supervisió control i configuració del sistema automatitzat.

La prévention du tabagisme et les facteurs organisationnels en médecine générale: une étude pilote en Suisse romande

Context: Several studies have been carried out to describe how general practitioners (GPs) follow smoking cessation counseling's recommendations and to identify GP-related factors that influence their practice. But limited information exists about practice organization's elements influencing smoking counseling and more generally about prevention activities in primary care (PC) in Switzerland. Objectives: Explore the feasibility of this study. Investigate determinants of PC practices associated with smoking cessation counseling in Switzerland. Explore the GP's attitude towards prevention and the organizational characteristics of PC practices. Design: Pilot Web-based survey in a representative sample of Swiss French speaking GPs. Results : 44 GP's responded; 66% were men; mean age = 57.5 years; 59% were in group practices; 1 GP was currently smoking and 32% were ex-smokers; 57% of GPs found very important to perform health prevention activities. 57% of GPs were trained (>5 hours throughout the career) to provide smoking cessation counseling. 84% of GP's always inquire about smoking status during first consultations, compared to 69% during emergency consultations for respiratory symptoms and only 9% during non-respiratory emergency consultation. Factors positively associated with smoking status inquiring were: young age (<57.5) of GP's for first consultations, rural location and solo practice for emergency consultations. Smoking cessation counseling is systematically provided by 48% of GPs during emergency consultations for respiratory symptoms and by 20% of GPs during follow-up consultations. Factor positively associated with smoking cessation counseling was solo practice. Discussion: In Switzerland, there are missed opportunities to provide smoking cessation counseling, especially in emergency situations, possibly in people who have rarely contacts with the health care system. Despite a small sample, this study showed the potential associations between organizational and GP-related factors and smoking cessation counseling. These findings will be further explored in a national study among 200 GPs' practices.