2,084 research outputs found

    6. Reading Wittgenstein Between the Texts

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    Sharing the “historicist challenge to analytic philosophy” (Glock) we investigate the philosophical production (and, to a lesser extent, some non-philosophical works as well) on Ludwig Wittgenstein from a distant reading perspective. First, we provide a description of the “Wittgensteinian field” by analyzing several data provided by the Philosopher’s Index, an electronic bibliographic database especially devoted to philosophy. Then we analyze these data by using statistical tools (such as for example topic modeling) and we interpret the results historically and sociologically, along the lines of Bourdieu on Heidegger, Lamont on Derrida, Gross on Rorty, and Collins on the whole philosophical tradition

    Rischio clinico, gestione del rischio e sue implicazioni. Un aspetto della medicina traslazionale

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    2015 - 2016This thesis is based on the awareness that prevention in the ethical and vocational training of health workers is extremely important, above all the one concerned with the clinical risk as well as a competent and intelligent management of daily professional practice. In the university curriculum, especially during internship, any future health worker should be guided to acquire the skills necessary to identify the clinical risks associated with the use of tools and technologies in specific professional contexts so that they can apply, in their professional practice, interventions for risk prevention and management. Prevention, recognition and risk management are today considered important aspects in the quality system and staff training, while in the past, attention has been paid mainly to risk structural aspects, such as the safety of environments and equipment or the prevention professional health risks represented by health interventions, just linked to legal action against the health organization. Today, they are more aware of the importance of an adverse event monitoring program and timely intervention not so much for a defensive medicine, but to promote active staffing by raising the level of safety and competence, with a view to continuous improvement of quality. Care quality comes not only from the effectiveness and efficiency of the benefits but also from the security of the service offered. The risk management, we mean, does not represent a kind of superstructure that imposes protocols and norms, but rather as heritage of knowledge, a culture of practicing medicine that invests steadily on training, communication, awareness raising and respect of the patient; In this context, clinical risk management paves the way for a more careful and close health culture close to the patient and the practitioners, hence more oriented towards the humanization of medicine (Leone 2007) and to respecting the identity and dignity of the man, just as article 2 of our Constitution says. The thesis presented here reflects upon the clinical risk, its management and its implications in view of the possible application of translational medicine. The work is divided into three parts. In the first, Clinical risk management analysis at hospital companies, after firstly defining the concept of clinical risk, analyzes the elements useful for risk identification and management, focusing on the most prevalent risk management models and related techniques. In the second part, The risk of cutting and tip injuries, having identified and analyzed the concept of biological risk and illustrated the epidemiology of puncture and cutting injuries, has focused on the reference norms. Finally, in the third part, the project, which is the empirical-experimental part of this thesis, is presented: the motivations, the various phases, the processing of the data, and the presentation, for each stage of the results. The thesis ends by presenting a formative intervention model, a communication plan that could be useful in the training of future health professionals to reduce clinical risk. 2 This is the innovative part of the research, at least in the intentions of the person who carried it out: the design of a communicative plan aimed at reducing the incidence of biological risk derived from accidental bites and, in particular, enriching the training path of future health works. On the other hand, in recent years, the literature on communication in clinical risk management has considerably increased in recent years, in line with the growing importance of the problem. Institutional documents of particular impact have been adopted in some countries: in Australia, the Open Disclosure Standard 2003 document, which emphasizes in particular the importance of communicating between health workers and health staff; In England, the National Patient Safety, which launched the "Being Open" campaign in 2005. In any case, communication has a central role in all areas of safety promotion for health workers; In fact it is a process that determines the effectiveness, efficiency and productivity of the organization, on the contrary, if inappropriate, incomplete or not transmitted in the most timely and convenient way, it contributes, to the onset (or increase) of risk factors. In the concluding reflections of this thesis we realize that, in addition to ethical and deontological reasons, transparent and honest communication of errors and avoidable events caused by cutting and tip injuries is essential to promote, strengthen and involve the health worker in a conscious manner Its use is essential to introduce and manage security systems and investigate the causative processes, as well as to identify and introduce corrective measures and promote system development; Correct communication also favors both the individual professional and the overall system organization, learning from the mistake and overall improvement of health practice. Communication is therefore promoted at system level but also made "competence and professional tool" of each operator and manager. In this sense, after a research data analysis, we propose the development of a protocol on specific communication methods in the risk of cutting and puncture injuries, which can ensure the adoption of homogeneous behavior by all staff. We are aware that there are some possible barriers to transparent communication of errors such as the absence or ambiguity of error-reporting policies, lack of support for reporting errors, fear of disciplinary action; The tendency to compete among clinicians, and often the precariousness of the workplace, it is important to stimulate an immediate analysis of the incident, an immediate and correct communication of events such as having a needle point during a take, an injection or in other way. Stimulating the reporting of the health problem, is not enough: a communication training plan is needed, stressing the importance of place and time, what to communicate, who and how. In order for communication to become a culture of security, in any case, it must be ensured clear and demonstrable and visual (nonverbal communication) conditions, as well as appropriate times, in order to avoid interference that may disturb the message you want to convey. 3 When you graduate, you need to plan some kind of training in the formation; in order to clarify whether the occurrence event has or has not caused the practitioner any harm or damage more or less important, it may still be useful to offer the opportunity of further meetings to get students comparing with the operator and build culture from an avoidable mistake; It is thus possible to think of bottom-up communication forms through which students can plan meetings where they can communicate, along the training plan they are running, methods and models to confront the risk of avoidable wounds and cuts with their mentors or academic tutors. Communication between professionals is a priority and vital within healthcare facilities. One of the critical areas in which internal communication is needed is to manage clinical risk and health security for health workers and the users community. Through appropriate communication and sharing within the group, the mistake can also become an extraordinary opportunity for learning and prevention. The moment of error communication is however delicate, as the idea of individual responsibility lies in culture. When an error occurs, you are accustomed to seeking a guilty person immediately, rather than the conditions that favored it. It is therefore necessary for a cultural change to reconsider the mistake as a learning opportunity instead of as a fault, thus creating the conditions for spontaneous reporting and the analysis of events to be avoided. Good internal communication and group work are essential for the success of the clinical risk management program and, more generally, for the implementation of clinical governance policies. The introduction of briefing as an organizational methodology to develop the security culture of and an instrument to prevent adverse events is an important opportunity for internal communication. In the final part, this thesis proposes to deepen (and eventually prepare and implement) new forms of interactive training in the possible communication and training plan, along with the existing guidelines; It is about experimenting a new guideline aimed at the forming protection in avoidable clinical risks, wounds and cuts, through active and participatory communication of health care graduates. Active communication includes some essential elements: listening and returning; the correct information to be followed by an argument explaining the facts supporting the message and the possible solutions that the message may convey; a concerted involvement of people in the management of risk prevention and control; the declared statement of the organizational commitment to possible future actions; the clear indication of the persons they are addressed to, the timing and the modalities, in order to obtain further information; throughout the training course, moreover, the key message should be repeated and repeated, in order to keep the communicative relationship with the participants alive. We are firmly convinced that only with training, communication and awareness of all hospital staff we can reduce the clinical risk associated with care, thus raising the level of quality and safety of care benefits, which is the nodal point of the Ph.D. project itself. [edited by author]Questa tesi di ricerca nasce dalla consapevolezza che nella formazione etica, deontologica e professionale degli operatori sanitari un posto di rilievo è occupato dal riconoscimento dell’importanza della prevenzione, in particolare, del rischio clinico e della capacità, nella pratica professionale quotidiana, di una sua gestione competente e intelligente. Nel curriculum formativo universitario, soprattutto durante il tirocinio, ogni futuro professionista sanitario dovrebbe essere guidato ad acquisire le competenze utili ad identificare i rischi clinici connessi anche all’uso di strumenti e tecnologie negli specifici contesti professionali, così da poter applicare, nella pratica professionale, interventi per la prevenzione e la gestione dei rischi. Prevenzione, riconoscimento e gestione dei rischi sono oggi considerati aspetti rilevanti nel sistema di qualità e nella formazione del personale mentre, in passato, si è prestata attenzione prevalentemente agli aspetti strutturali (del rischio), quali ad esempio la sicurezza degli ambienti e delle attrezzature o la prevenzione dei rischi (professionali) rappresentati da interventi sanitari, solo o prevalentemente se collegati ad azioni legali contro l’organizzazione sanitaria. Oggi si è più consapevoli dell’importanza di un programma di monitoraggio degli eventi avversi e di un intervento tempestivo non tanto per una medicina, per così dire, difensiva, ma per la promozione della partecipazione attiva del personale, innalzandone il livello di sicurezza, oltre che di competenza, in un’ottica di miglioramento continuo della qualità. La qualità delle cure discende non solo dall’efficacia e dall’efficienza delle prestazioni, ma anche dalla sicurezza del servizio offerto. La gestione del rischio, così intesa, non rappresenta una sorta di sovrastruttura che impone protocolli e norme, bensì come un patrimonio di conoscenze, una cultura della pratica medicina che investa in modo costante sulla formazione, sulla comunicazione, sulla sensibilizzazione alla cura e al rispetto del paziente; in quest’ottica, il clinical risk management apre la strada ad una cultura della salute più attenta e vicina al paziente e agli operatori, dunque maggiormente orientata all’umanizzazione della medicina (Leone 2007) e al rispetto dell’identità e della dignità dell’uomo, così come recita anche l’art. 2 della nostra Costituzione. La tesi qui presentata riflette intorno al rischio clinico, alla sua gestione e alle sue implicazioni in un’ottica di possibile applicazione di Medicina traslazionale. Il lavoro si divide in tre parti. Nella prima, Analisi del clinical risk management nelle aziende ospedaliere, dopo una prima definizione del concetto di rischio clinico, si analizzano gli elementi utili alla identificazione e alla gestione del rischio, soffermandosi, in particolare sui prevalenti Modelli di gestione del rischio e sulle relative Tecniche. Nella seconda parte, Il rischio da ferite da taglio e da punta, dopo aver individuato e analizzato il concetto di rischio biologico e aver illustrato l’epidemiologia delle ferite da punta e da taglio, ci si è soffermati sulla normativa di riferimento. Nella terza parte, infine, si è presentato il progetto che costituisce la parte empirico-sperimentale della presente tesi: le motivazioni, le vari fasi, l’elaborazione dei dati, con la presentazione, per ogni fase dei risultati. Conclude la tesi la presentazione di un modello di intervento formativo, un piano comunicativo che possa essere utile, nel percorso formativo dei futuri professionisti sanitari, alla riduzione del rischio. È questa la parte innovativa della ricerca, almeno nelle intenzioni di chi l’ha effettuata: la progettazione di un piano comunicativo finalizzato a ridurre l’incidenza di rischio derivato dalle punture accidentali e rivolto, in modo particolare, ad arricchire il percorso formativo del futuro professionista sanitario. D’altra parte, in corrispondenza alla crescente rilevanza della problematica, negli ultimi anni, a livello internazionale, è notevolmente aumentata la letteratura relativa alla comunicazione nella gestione del rischio clinico. Documenti istituzionali di particolare impatto sono stati adottati in alcuni paesi, tra cui si citano, ad esempio: in Australia, il documento Open Disclosure Standard, del 2003, che sottolinea, in particolare, l’importanza della comunicazione degli operatori tra di loro e con tutto l’altro personale della azienda sanitaria; in Inghilterra, la National Patient Safety, che ha lanciato, nel 2005, la campagna Being Open. Centrale risulta, in ogni caso, il ruolo della comunicazione, in tutti gli ambiti della promozione della sicurezza per i professionisti della salute; infatti costituisce un processo che determina efficacia, efficienza e produttività della organizzazione, contribuendo, al contrario, se non appropriata, incompleta o non trasmessa nei tempi e nei modi più opportuni, all’insorgenza (o all’aumento) di fattori di rischio. Emerge, nelle riflessioni conclusive della tesi che, oltre a ragioni etiche e deontologiche, una comunicazione trasparente ed onesta degli errori e degli eventi evitabili provocati da ferite da taglio e da punta è essenziale per promuovere, rafforzare e coinvolgere in modo consapevole il professionista sanitario nelle eventuali modifiche del proprio operare professionale. Il suo impiego è essenziale nelle attività di introduzione e gestione dei sistemi per la sicurezza e nella effettuazione di indagini per l’accertamento dei processi determinanti, così come nella identificazione ed introduzione di misure correttive e di promozione dello sviluppo del sistema; una corretta comunicazione favorisce, inoltre, sia per il singolo professionista sia per la relativa organizzazione generale di sistema, l’apprendimento dall’errore ed il miglioramento complessivo della pratica sanitaria. La comunicazione va, dunque, promossa a livello di sistema ma anche resa “competenza e strumento professionale” di ciascun operatore e dirigente. In questo senso, dopo un’analisi dei dati della ricerca, si propone l’elaborazione di un protocollo sulle modalità di comunicazione specifica nel rischio da ferite da taglio e da punta, che possa garantire l’adozione di un comportamento omogeneo da parte di tutto il personale. Nella consapevolezza che vi sono alcune possibili barriere ad una comunicazione trasparente degli errori quali l’assenza o l’ambiguità delle politiche riguardanti la comunicazione dell’errore, l’assenza di supporto alla segnalazione degli errori, il timore di azioni disciplinari; la tendenza alla competizione tra clinici, nonché, spesso, la precarietà del posto di lavoro, è importante incentivare una immediata analisi dell’accaduto, una immediata e corretta comunicazione di eventi quali quello di essersi punti con un ago durante un prelievo, un’iniezione o in altro modo. Non è sufficiente incentivare la segnalazione dell’errore sanitario: occorre un piano di formazione alla comunicazione, in cui sia evidenziata anche l’importanza del luogo e del tempo, di cosa comunicare, a chi e come. Perché la comunicazione possa diventare cultura della sicurezza, debbono, in ogni caso, essere assicurate condizioni di chiarezza e dimostrazione anche visiva (comunicazione non verbale), nonché tempi adeguati, al fine di evitare interferenze che possano disturbare il messaggio che si vuole trasmettere. Quando si formano i laureandi, occorre pianificare una sorta di formazione nella formazione; volendo chiarire se l’evento dell’essersi punti abbia o non abbia causato al professionista alcun danno o un danno più o meno importante, può comunque essere utile offrire l’opportunità di effettuare ulteriori incontri, mettendo a confronto gli studenti con l’operatore in questione per una discussione che costruisca cultura partendo da un errore evitabile; è così possibile pensare a forme di comunicazione bottom-up, mediante le quali gli studenti possono pianificare incontri nei quali loro stessi possano comunicare, lungo il piano di formazione che stanno seguendo, metodi e modelli per confrontarsi sul rischio evitabile da ferite e da tagli con i loro mentoring o tutor accademici. La comunicazione tra professionisti è prioritaria e vitale all’interno delle strutture sanitarie. Una delle aree critiche in cui c’è bisogno di sviluppare la comunicazione interna è proprio la gestione del rischio clinico e la sicurezza sanitaria per i professionisti sanitari e per la comunità degli utenti. Attraverso un’adeguata comunicazione e condivisione all’interno del gruppo, anche l’errore può divenire una straordinaria occasione di apprendimento e di prevenzione. Il momento di comunicazione dell’errore è comunque delicato, perché nella cultura è radicata l’idea di responsabilità individuale. Quando avviene un errore, si è abituati a ricercare immediatamente un colpevole, piuttosto che le condizioni che lo hanno favorito. È necessario quindi un cambiamento culturale per riconsiderare l’errore come un’occasione di apprendimento anziché come una colpa, creando così i presupposti per la segnalazione spontanea e l’analisi degli eventi da evitare. Una buona comunicazione interna ed il lavoro di gruppo sono essenziali per il successo del programma di gestione del rischio clinico e, più in generale, per l’attuazione delle politiche di governo clinico. L’introduzione del briefing come metodologia organizzativa per lo sviluppo della cultura della promozione della sicurezza e strumento per la prevenzione degli eventi avversi costituisce una occasione importante di comunicazione interna. Nel possibile piano comunicativo-formativo, in chiusura di tesi, accanto al rispetto delle linee guida già esistenti, si propone di approfondire (e, eventualmente, predisporre e implementare) nuove forme interattive di formazione-comunicazione; si tratta di sperimentare una sorta di linea guida tesa alla formazione della tutela nei rischi clinici evitabili, tra cui ferite e tagli da punta, mediante una comunicazione attiva e partecipata dei laureandi delle professioni sanitarie. Una comunicazione attiva include alcuni elementi essenziali: l’ascolto e la sua restituzione; l’informazione corretta cui deve seguire un’argomentazione in cui siano esplicitati i fatti a sostegno del messaggio e le possibili soluzioni che il messaggio può prospettare; un coinvolgimento concordato delle persone nella gestione della prevenzione e del contenimento del rischio; l’esplicitazione dichiarata dell’impegno organizzativo sulle possibili azioni future; l’indicazione chiara delle persone cui rivolgersi, dei tempi e delle modalità, al fine di ottenere ulteriori informazioni; in tutto il percorso formativo, inoltre, andrebbe più volte riassunto e ripetuto il messaggio chiave, al fine di mantenere sempre viva la relazione comunicativa con i partecipanti. Siamo fermamente convinti che solo con la formazione, la comunicazione e la sensibilizzazione di tutto il personale ospedaliero si può ridurre il rischio clinico correlato all’assistenza, innalzando, di conseguenza, il livello della qualità e della sicurezza delle prestazioni assistenziali, punto nodale dello stesso progetto del Dottorato di ricerca. [a cura dell'autore]XV n.s. (XXIX

    A Refined Single Cell Landscape of Haematopoiesis in the Mouse Foetal Liver

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    During prenatal life, the foetal liver is colonised by several waves of haematopoietic progenitors to act as the main haematopoietic organ. Single cell (sc) RNA-seq has been used to identify foetal liver cell types via their transcriptomic signature and to compare gene expression patterns as haematopoietic development proceeds. To obtain a refined single cell landscape of haematopoiesis in the foetal liver, we have generated a scRNA-seq dataset from a whole mouse E12.5 liver that includes a larger number of cells than prior datasets at this stage and was obtained without cell type preselection to include all liver cell populations. We combined mining of this dataset with that of previously published datasets at other developmental stages to follow transcriptional dynamics as well as the cell cycle state of developing haematopoietic lineages. Our findings corroborate several prior reports on the timing of liver colonisation by haematopoietic progenitors and the emergence of differentiated lineages and provide further molecular characterisation of each cell population. Extending these findings, we demonstrate the existence of a foetal intermediate haemoglobin profile in the mouse, similar to that previously identified in humans, and a previously unidentified population of primitive erythroid cells in the foetal liver

    Reading Wittgenstein Between the Texts

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    Sharing the “historicist challenge to analytic philosophy” (Glock 2006) we investigate the philosophical production (and, to a lesser extent, some non-philosophical works as well) on Ludwig Wittgenstein from a distant reading perspective. First, we provide a description of the “Wittgensteinian field” by analyzing several data provided by the Philosopher’s Index, an electronic bibliographic database especially devoted to philosophy. Then we analyze these data by using statistical tools (such as for example topic modeling) and we interpret the results historically and sociologically, along the lines of Bourdieu (1988) on Heidegger, Lamont (1992) on Derrida, Gross (2006) on Rorty, and Collins (1999) on the whole philosophical tradition

    Relationship between health, lifestyle, psychosocial factors and academic performance: a cross-sectional study at the University of Salerno

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    Background: The relationship between health indicators and quality of life is significantly important in clinical decisions. Health policy and an individual’s quality of life are important factors contributing to an individual's decisions and preferences. University students constitute a large part of the country's young population, so a healthy lifestyle is of crucial importance for this group. The aim of the present study was to investigate healthy lifestyle habits and its relationship with academic performance in undergraduate students of the University of Salerno. Methods: A cross-sectional study was conducted among undergraduate students of the University of Salerno. Data were collected by a self-report anonymous questionnaire. The field research was conducted among students of the University of Salerno in the academic years 2014/2015, from October to March. Descriptive statistics were used to describe sample characteristics. Test of proportions was used to test the differences between blocked and regular students. Analysis were conducted using STATA software. Results: A total of 519 students formed the sample. In total, 248 (47.78%) claimed to have blocks in their studies and among them 214 (86.29%) were out of course. The status of blocked students’ health promotion behaviors was significantly favorable compared to that of regular students. General health perception of the regular students yielded worse results than of the blocked students. Anxiety and depression were greater in regular students than blocked students. Conclusion: Results from the present study support our hypothesis of a relationship between health, lifestyle, psychosocial factors and academic performance: students with blocked had better health and lifestyle than regular students. Their attitude to resilience emerged from the ability to overcome difficult situations, but also from an attitude of arrogance despite being aware of the ability to study successfully. Probably the blocked in the studies was due to low self-esteem

    Internet Addiction: a prevention action-research intervention

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    The aim of this paper was to present an action-research intervention for the prevention of Internet addiction (IA) in schools. Applying a pre-experimental research design model, a total of 90 young subjects (45 males and 45 females) were treated using a peer education programme. The Internet Addiction Test was used as a screening tool pre- and post-treatment and analysed using a paired t-test. The results showed a significant positive difference in the post-treatment values for both males and females. This research highlights the link between IA and cultural and social aspects of the disease in addition to discussing the difficulties of IA prevention.&nbsp

    Glutamate-mediated blood-brain barrier opening. implications for neuroprotection and drug delivery

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    The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT: In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders

    Improving total body irradiation with a dedicated couch and 3D-printed patient-specific lung blocks: A feasibility study

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    Introduction: Total body irradiation (TBI) is an important component of the conditioning regimen in patients undergoing hematopoietic stem cell transplants. TBI is used in very few patients and therefore it is generally delivered with standard linear accelerators (LINACs) and not with dedicated devices. Severe pulmonary toxicity is the most common adverse effect after TBI, and patient-specific lead blocks are used to reduce mean lung dose. In this context, online treatment setup is crucial to achieve precise positioning of the lung blocks. Therefore, in this study we aim to report our experience at generating 3D-printed patient-specific lung blocks and coupling a dedicated couch (with an integrated onboard image device) with a modern LINAC for TBI treatment. Material and methods: TBI was planned and delivered (2Gy/fraction given twice a day, over 3 days) to 15 patients. Online images, to be compared with planned digitally reconstructed radiographies, were acquired with the couch-dedicated Electronic Portal Imaging Device (EPID) panel and imported in the iView software using a homemade Graphical User Interface (GUI). In vivo dosimetry, using Metal-Oxide Field-Effect Transistors (MOSFETs), was used to assess the setup reproducibility in both supine and prone positions. Results: 3D printing of lung blocks was feasible for all planned patients using a stereolithography 3D printer with a build volume of 14.5×14.5×17.5 cm3. The number of required pre-TBI EPID-images generally decreases after the first fraction. In patient-specific quality assurance, the difference between measured and calculated dose was generally<2%. The MOSFET measurements reproducibility along each treatment and patient was 2.7%, in average. Conclusion: The TBI technique was successfully implemented, demonstrating that our approach is feasible, flexible, and cost-effective. The use of 3D-printed patient-specific lung blocks have the potential to personalize TBI treatment and to refine the shape of the blocks before delivery, making them extremely versatile

    Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells

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    Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the –161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis- regulatory elements within this –161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells
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