The role of the radiotherapy technologist in gamma knife radiosurgery within a multidisciplinary team: the Lausanne experience

Objective: Integration of the radiotherapy technologist "know-how" in the Gamma Knife treatment processMaterials and Methods: Gamma Knife (GK) treatments started in July 2010 at the GK Center in C.H.U.V. with the Leksell Gamma KnifeR Perfexion?(Elekta AB, Sweden). The multidisciplinary GK team involves neurosurgeons, radio-oncologists, physicists, neuroradiologists, nurses and technologists, aiming at a full integration for optimal patient management.Results: Between July and December 2010, 60 patients have been treated. Required stereotactic imaging involves IRM, CT scan (and angiography for AVM). All the steps in the treatment process (Leksell coordinate frame fixation, imaging, planning, treatment) are supervised by the members of the multidisciplinary team. In our experience, radiotherapy technologist (RTT) have acquired an important role in the multidisciplinary team communication and integration. Specifically, the RTT are responsible of: supervision of the image acquisition, performing the Gamma Knife unit control tests, patient setup, and patient surveillance during treatment.Conclusion: RTT have a fundamental role in the communication within the team, between the team and the patient and also to assure the patient security. Our experience shows that it is possible and required to involve RTT in all steps of the GK treatment process, to guarantee the best GK treatment possible.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

The GENCODE pseudogene resource.

BACKGROUND: Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data. RESULTS: As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection. CONCLUSIONS: At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.

Worlds of working poverty : Cross-national variation in the mechanisms that lead to poverty among workers

The objective of this paper is to distinguish between different types of working poverty, on the basis of the mechanisms that produce it. Whereas the poverty literature identifies a myriad of risk factors and of categories of disadvantaged workers, we focus on three immediate causes of working poverty, namely low wage rate, weak labour force attachment, and high needs, the latter mainly due to the presence of children (and sometimes to the increase in needs caused by a divorce). These three mechanisms are the channels through which macroeconomic, demographic and policy factors have a direct bearing on working households. The main assumption tested here is that welfare regimes strongly influence the relative weight of these three mechanisms in producing working poverty, and, hence, the composition of the working-poor population. Our figures confirm this hypothesis and show that low-wage employment is a key factor, but, by far, not the only one and that family policies broadly understood play a decisive role, as well as patterns of labour market participation and integration.

Autonomia i inclusió dels alumnes d'educació infantil a l'escola rural: les conferències a l'escola La Popa de Castellcir

El tema central d’aquest Treball Final de Grau és l’autonomia dels alumnes d’educació infantil a l’escola rural. Aquest projecte està organitzat a partir de dos grans blocs. En el primer bloc hi trobem el marc teòric, on es desglossen totes els aspectes importants i característics de l’escola rural i les seves estratègies didàctiques, a banda de definir i recercar en el concepte d’autonomia. En el segon bloc hi trobem la part pràctica i el treball de camp. Aquest apartat es desenvolupa al voltant de l’estratègia didàctica de les conferències a l’escola La Popa de Castellcir que s’analitzen i s’avaluen per tal de conèixer com aquesta estratègia potencia l’autonomia i la inclusió dels infants a l’etapa d’educació infantil.

MR connectomics: a conceptual framework for studying the developing brain.

THE COMBINATION OF ADVANCED NEUROIMAGING TECHNIQUES AND MAJOR DEVELOPMENTS IN COMPLEX NETWORK SCIENCE, HAVE GIVEN BIRTH TO A NEW FRAMEWORK FOR STUDYING THE BRAIN: "connectomics." This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research.

Ontología de ALUS

En este trabajo se describe una base de conocimiento de las ALU humanas. La ontología incorpora términos SO y GO y está orientada a describir el contexto genómico del conjunto de ALU. Para cada elemento ALU se almacenan el gen y transcrito más cercanos, así como su anotación funcional de acuerdo a GO, el estado de la cromatina circundante y los factores de transcripción presentes en la ALU. Se han incorporado reglas semánticas para facilitar el almacenamiento, consulta e integración de la información. La ontología de ALU es plenamente analizable mediante razonadores como Pellet y está parcialmente transferida a una wiki semántica.

Maahanmuuttajaoppilaat erityiskouluissa

Immigrant Pupils in Special Education Schools The study focused on the opinions of immigrant pupils in the 1st–9th grades of basic education in four special education schools of the City of Turku and in need of special support about the following: 1. Their difficulties in going to school in general education before the transfer to a special education school. 2. Their opinions about the transfer process to special education and the changes in their school practice after being transferred to a special education school. 3. Their experiences about their school and coping in special education school. The study strengthened the idea that immigrant pupils need positive special treatment, linguistic support, individual guidance, small teaching groups and operating models that promote well-being on their integration and education path. The central educational idea of inclusive education is based on deconstructing the power structures concerning gender, ethnicity and “race” and approval of differences in the pupils. Shifting the emphasis from the pupil to working on the learning environment has resulted in special education no longer being primarily separate special education tied to a certain place, but directing the teaching more towards individuality. The central dimension of intercultural competence of a teacher working in a multicultural class seems to be the attitudes and approaches to a different pupil; the teacher must be interculturally sensitive when facing children and young people from a foreign culture. Education and teaching affect every sector of the pupil’s well-being. Learning and learning results have a connection with teaching, education and well-being. Every sector is important for the going to school and integration of an immigrant pupil in need of special support. The basis of the study is the equality of opportunities and the humanistic idea of the human being in the Finnish education policy. The immigrant pupils selected for the study represented the following language groups: Arabian, Albanian, Somali, Russian and Vietnamese. In the four special education schools, the number of immigrant pupils belonging to these language groups (2004) totalled 104. A total of 89 pupils i.e. 86% answered the questionnaire, which is sufficient considering the generalisation of the study. Although this is basically a quantitative study, the interviewing method was used in part of the study, because the questionnaires were in Finnish and consequently, it was difficult for some immigrant pupils to understand them. Understanding the questions was also affected by the fact that the age distribution in the study was very wide (7–18). According to the results of the study, the immigrants felt that the biggest drawbacks in general education were their inability to speak Finnish and lack of concentration. The actual process of being transferred to a special education class remained unclear for immigrant pupils, and they could do very little about the transfer themselves. The results show that immigrant pupils coped well in special education school; they felt that their learning ability and concentration improved in the small groups of the special education school. They considered the individual support given in the special education schools to be useful. The lower-grade immigrant pupils had a more positive attitude towards special education school than the upper-grade immigrant pupils. In all the special education schools the immigrant pupils experienced that they were in a good position in the class; girls felt this even a little more strongly than boys. The teacher-pupil-relationship was felt to be good. School bullying being so common was a negative feature experienced by immigrant pupils, who were often targets or bullies themselves. Immigrant pupils believed in their success at school and in the opportunities offered by special education schools. Generally they were of the opinion that pupils are not labelled by special school; however, upper-grade immigrant pupils were more hesitant than lower-grade immigrant pupils. This study aimed at bringing out the immigrant pupils’ own opinions. Teaching immigrant pupils in special education schools has not been very much studied in Finland, which made the topic new and even more challenging.

Web-palveluiden turvallisuus tietojärjestelmien välisessä integraatiossa

Tämän diplomityön tavoitteena oli tutkia liiketoiminnallisessaympäristössä olevia Web-palvelu -teknologialla toteutettujen integraatioprojektien tietoturvaa. Web-palvelut ovat SOAP-muotoisia HTTP-protokollalla välitettäviä viestejä, joilla voidaan välittää tietoa tietojärjestelmästä toiseen tai suorittaa liiketoiminnan tapahtumia. Työssä käsiteltiin erilaisia tietoturvallisuuteen vaikuttavia osa-alueita ja niiden sopivuutta Web-palveluihin. Tietoturvaa on käsitelty enimmäkseen liiketoiminnallisesta näkökulmasta. Työssä havaittiin tietoturvan koostuvan monesta osa-alueesta. Osa-alueista muodostuutietoturvallinen kokonaisuus, jossa on mukana valitut teknologiat, haluttu tietoturvallisuuden taso, integroitavat tietojärjestelmät sekä näiden yhteenliittäminen ja prosessit. Jokaisen integraatioprojektin ollessa oma kokonaisuutensa, on yleispätevän tietoturvan rakentaminen vaikeaa. Tämän seurauksena tietoturvaa tulee käsitellä jatkuvasti integraatioprojektin eri vaiheissa tietoturvan vaatimusten mukaan.

Hydraulisen kuristinmallin ja liikealustan ohjauksen kehittäminen reaaliaikasimulointiin

Diplomityön ensimmäisessä vaiheessa tutkittiin hydraulisen kuristimen ominaisuuksia ja esiteltiin numeerisesti tehokas kuristinmalli käyttäenpolynomifunktiota virtauksen laminaarisen ja transitioalueen kuvaukseen. Puoliempiirisen mallin paremmuus tulee esille siinä, että kuristimen geometriatietoja ei tarvita laskettaessa virtausta paine-eron perusteella. Reaaliaikasimuloinnissa esiintyy kompromisseja tarkkuuden ja laskentanopeuden välillä. Tätä asiaa tutkittiin kahden virtausalueen kuristinmallilla. Transition paine-eron ja integrointiaika-askelen valinnan vaikutus tarkkuuteen ja laskentanopeuteen tutkittiin. Toisessa vaiheessa tutkittiin mahdollisimman hyvän liiketuntuman tuottamista liikealustalla ohjaussignaalia kehittämällä. Liikealustan liikeradan rajallisuudesta johtuen ohjauksessa on perinteisesti käytetty washout-suodatusta, joka erottelee simuloitavan järjestelmän kiihtyvyyssignaalista vain nopeatkiihtyvyydet. Tässä työssä tutkittiin hitaiden kiihtyvyyksien ottamista mukaan liikealustan ohjaukseen liikealustan liikeradan puitteissa. Tämä toteutettiin kuvaamalla hitaat kiihtyvyydet kallistamalla liikealustaa, jolloin käyttäjään kohdistuva voima saatiin kuvattua gravitaatiota hyväksi käyttäen.

Polttoaineiden vastaanotonja käytön tarkastelu ja optimointi biopolttoaineita käyttävässä voimalaitoksessa

Kioton pöytäkirja velvoittaa teollisuusmaita vähentämään hiilidioksidipäästöjään. Energiantuotantolaitosten on vähennettävä tuotantoaan tai siirryttävä käyttämään vähäpäästöisempiä polttoaineita vähennystavoitteiden saavuttamiseksi. Etelä-Savon Energia Oy Mikkelissä rakentaa uuden kattilalaitoksen, joka soveltuu hiilidioksidivapaiden puupolttoaineiden polttoon. Kun uusi kattilalaitos otetaan käyttöön, kasvaa voimalaitoksen polttoaineiden kulutus 1,7 -kertaiseksi. Tämä merkitsee laitokselle tulevien polttoainekuljetusten määrän kasvamista kylmimpinä aikoina yli 70:neen autoon vuorokaudessa. Työssä on tarkasteltu nykyisen polttoaineiden vastaanoton ja kuljettimien kykyä ottaa vastaan kasvavat polttoainevirrat. Vastaanoton sujuvuus on polttoaineiden laadunhallinnan lisäksi edellytys laitoksen käytölle. Työn tavoitteena on ollut kartoittaa vastaanoton ongelmakohtia ja löytää näihin parannusmahdollisuuksia. Vastaanottokapasiteetti tulee venymään äärimmilleen tulevaisuudessa. Jotta määrällisesti riittävä ja laadullisesti sopiva polttoaineseos saadaan vastaanotettua nykyisenä vastaanottoaikana, tulee autojen saapua entistä tasaisemmin laitokselle. Tasainen saapuminen on mahdollista aikatauluttamalla sopivasti polttoainekuljetusten saapumisajat laitokselle. Vastaanoton kapasiteettia voitaisiin nostaa kasvattamalla kenttävaraston kokoa ja pienillä muutoksilla vastaanottoasemissa. Polttoaineen laadun ja vastaanoton tarkastelun lisäksi työssä on tarkasteltu polttoaineen saatavuutta.

Managing Business Processes in Corporate Expansion

Yrityksen laajentuessa kansainvälisesti, olemassa olevat rutiinit jäävät vanhoiksi ja liiketoimintaprosessien johtaminen muuttuu. Kyseisten prosessien täytyy olla läpinäkyviä ja tietovirtojen hyvin suunniteltuja. Prosessien harmonisointi aiheuttaa haasteita yrityksessä ja konsernin etu tulee ottaa huomioon. Ahlstrom konserni laajentuu merkittävästi kaikilla liiketoiminta-alueillaan ja kansainvälinen laajentuminen vie Ahlstrom Glassfibre Oy:n täysin uuteen tilanteeseen. Liiketoimintaprosessien johtamiseen vaikuttavat konsernin ohjaus, mahdollisuudet muutosten implementoimiseksi, toimintaympäristön tekijät ja järjestelmien muodostama arkkitehtuuri. Tässä tutkimuksessa keskitytään ydinprosessien tietovirtoihin ja työ on tehty Karhulan tehtaalla Suomessa. Johtamismallin luomiseksi vaaditaan yrityksessä ongelmia määrittelevää työskentelyä. Tämä ongelmanmääritys oli työn tärkein tavoite. Ongelma-alueiden tutkimuksen pohjalta muodostettiin ratkaisu, jossa käsiteltiin systemaattisen liiketoimintaprosessien johtamisen mahdollisuuksia ja vaatimuksia. Lopputuloksena voidaan todeta, että suurin painopiste löytyy informaatioteknologian ja liiketoiminnan rajapinnoista. Tähän työhön liittyvät myös prossien harmonisointi ja integrointi.

Functions of the human papillomavirus type 16 E4 protein

1. Abstract Cervical cancer is thought to be the consequence of infection by human papillomaviruses (HPV). In the majority of cases, DNA from HPV type 16 (HPV16) is found in malignant cervical lesions. The initial steps leading to transformation of an infected cell are not clearly understood but in most cases, disruption and integration of the episomal viral DNA must take place. As a consequence, the E2 and E4 genes are usually not expressed whereas the E6 and E7 oncogenes are highly expressed. However, in a normal infection in which the viral DNA is maintained as an episome, all viral genes are expressed. The pattern according to which the viral proteins are made, and therefore the life cycle of the virus, is tightly linked to the differentiation process of the host keratinocyte. The study of the viral oncogenes E6 and E7 has revealed crucial functions in the process of malignant transformation such as degradation of the p53 tumor suppressor protein, deregulation of the Retinoblastoma protein pathway and activation of the telomerase ribonucleoprotein. All these steps are necessary for cancerous lesions to develop. However, the loss of the E2 gene product seems to be necessary for sufficient expression of E6 and E7 in order to achieve such effects. In normal infections, the E4 protein is made abundantly in the later stages of the viral life cycle. Though extensive amounts of work have been carried out to define the function of E4, it still remains unclear. In this study, several approaches have been used to try and determine the functions of E4. First, a cell-penetrating fusion protein was designed and produced in order to circumvent the chronic difficulties of expressing E4 in mammalian cells. Unfortunately, this approach was not successful due to precipitation of the purified fusion protein. Second, the observation that E4 accumulates in cells having modified their adhesion properties led to the hypothesis that E4 might be involved in the differentiation process of keratinocytes. Preliminary results suggest that E4 triggers differentiation. Last, as E4 has been reported to collapse the cytokeratin network of keratinocytes, a direct approach using atomic force microscopy has allowed us to test the potential modification of mechanical properties of cells harboring reorganized cytokeratin networks. If so, a potential role for E4 in viral particle release could be hypothesized. 2. Résumé Il a été établi que le cancer du col de l'utérus se développe essentiellement à la suite d'une infection par le virus du papillome humain (HPV). Dans la majorité des cas analysés, de l'ADN du HPV de type 16 (HPV16) est détecté. Les étapes initiales de la transformation d'une cellule infectée sont mal connues mais il semble qu'une rupture du génome viral, normalement épisomal, suivi d'une intégration dans le génome de la cellule hôte soient des étapes nécessaires dans la plupart des cas. Or il semble qu'il y ait une sélection pour les cas où l'expression des oncogènes viraux E6 et E7 soit favorisée alors que l'expression des gènes E2 et E4 est en général impossible. Par contre, dans une infection dite normale où le génome viral n'est pas rompu, il n'y pas développement de cancer et tous les gènes viraux sont exprimés. L'ordre dans lequel les protéines virales sont produites, et donc le cycle de réplication du virus, est intimement lié au processus de différentiation de la cellule hôte. L'étude des protéines oncogènes E6 et E7 a révélé des fonctions clés dans le processus de transformation des cellules infectées telles que la dégradation du suppresseur de tumeur p53, la dérégulation de la voie de signalisation Rb ainsi que l'activation de la télomérase. Toutes ces activités sont nécessaires au développement de lésions cancéreuses. Toutefois, il semble que l'expression du gène E2 doit être empêchée afin que suffisamment des protéines E6 et E7 soient produites. Lorsque le gène E2 est exprimé, et donc lorsque le génome viral n'est pas rompu, les protéines E6 et E7 n'entraînent pas de telles conséquences. Le gène E4, qui se trouve dans la séquence codante de E2, a aussi besoin d'un génome viral intact pour être exprimé. Dans une infection normale, le gène E4 est exprimé abondamment dans les dernières étapes de la réplication du virus. Bien que de nombreuses études aient été menées afin de déterminer la fonction virale à E4, aucun résultat n'apparaît évident. Dans ce travail, plusieurs approches ont été utilisées afin d'adresser cette question. Premièrement, une protéine de fusion TAT-E4 a été produite et purifiée. Cette protéine, pouvant entrer dans les cellules vivantes par diffusion au travers de la membrane plasmique, aurait permis d'éviter ainsi les problèmes chroniques rencontrés lors de l'expression de E4 dans les cellules mammifères. Malheureusement, cette stratégie n'a pas pu être utilisée à cause de la précipitation de la protéine purifiée. Ensuite, l'observation que E4 s'accumule dans les cellules ayant modifié leurs propriétés d'adhésion a suggéré que E4 pourrait être impliqué dans le procédé de différentiation des kératinocytes. Des résultats préliminaires supportent cette possibilité. Enfin, il a été montré que E4 pouvait induire une réorganisation du réseau des cytokératines. Une approche directe utilisant le microscope à force atomique nous a ainsi permis de tester une potentielle modification des propriétés mécaniques de cellules ayant modifié leur réseau de cytokératines en présence de E4. Si tel est le cas, un rôle dans la libération de particules virales peut être proposé pour E4.

Recommendations for the use of multimodal monitoring in the neurointensive care unit.

PURPOSE OF REVIEW: Multimodal monitoring (MMM) is routinely applied in neurointensive care. Unfortunately, there is no robust evidence on which MMM-derived physiologic variables are the most clinically relevant, how and when they should be monitored, and whether MMM impacts outcome. The complexity is even higher because once the data are continuously collected, interpretation and integration of these complex physiologic events into targeted individualized care is still embryonic. RECENT FINDINGS: Recent clinical investigation mainly focused on intracranial pressure, perfusion of the brain, and oxygen availability along with electrophysiology. Moreover, a series of articles reviewing the available evidence on all the MMM tools, giving practical recommendations for bedside MMM, has been published, along with other consensus documents on the role of neuromonitoring and electroencephalography in this setting. SUMMARY: MMM allows comprehensive exploration of the complex pathophysiology of acute brain damage and, depending on the different configuration of the pathological condition we are treating, the application of targeted individualized care. Unfortunately, we still lack robust evidence on how to better integrate MMM-derived information at the bedside to improve patient management. Advanced informatics is promising and may provide us a supportive tool to interpret physiologic events and guide pathophysiological-based therapeutic decisions.