Medicalgenomics.org : an open source database and retrieval system for biomedical analysis

Die Molekularbiologie von Menschen ist ein hochkomplexes und vielfältiges Themengebiet, in dem in vielen Bereichen geforscht wird. Der Fokus liegt hier insbesondere auf den Bereichen der Genomik, Proteomik, Transkriptomik und Metabolomik, und Jahre der Forschung haben große Mengen an wertvollen Daten zusammengetragen. Diese Ansammlung wächst stetig und auch für die Zukunft ist keine Stagnation absehbar. Mittlerweile aber hat diese permanente Informationsflut wertvolles Wissen in unüberschaubaren, digitalen Datenbergen begraben und das Sammeln von forschungsspezifischen und zuverlässigen Informationen zu einer großen Herausforderung werden lassen. Die in dieser Dissertation präsentierte Arbeit hat ein umfassendes Kompendium von humanen Geweben für biomedizinische Analysen generiert. Es trägt den Namen medicalgenomics.org und hat diverse biomedizinische Probleme auf der Suche nach spezifischem Wissen in zahlreichen Datenbanken gelöst. Das Kompendium ist das erste seiner Art und sein gewonnenes Wissen wird Wissenschaftlern helfen, einen besseren systematischen Überblick über spezifische Gene oder funktionaler Profile, mit Sicht auf Regulation sowie pathologische und physiologische Bedingungen, zu bekommen. Darüber hinaus ermöglichen verschiedene Abfragemethoden eine effiziente Analyse von signalgebenden Ereignissen, metabolischen Stoffwechselwegen sowie das Studieren der Gene auf der Expressionsebene. Die gesamte Vielfalt dieser Abfrageoptionen ermöglicht den Wissenschaftlern hoch spezialisierte, genetische Straßenkarten zu erstellen, mit deren Hilfe zukünftige Experimente genauer geplant werden können. Infolgedessen können wertvolle Ressourcen und Zeit eingespart werden, bei steigenden Erfolgsaussichten. Des Weiteren kann das umfassende Wissen des Kompendiums genutzt werden, um biomedizinische Hypothesen zu generieren und zu überprüfen.

Migrazione concorrente di macchine virtuali su piattaforme open source

Questa tesi si pone l’obiettivo di effettuare un’analisi aggiornata sulla recente evoluzione del Cloud Computing e dei nuovi modelli architetturali a sostegno della continua crescita di richiesta di risorse di computazione, di storage e di rete all'interno dei data center, per poi dedicarsi ad una fase sperimentale di migrazioni live singole e concorrenti di macchine virtuali, studiandone le prestazioni a livello di risorse applicative e di rete all’interno della piattaforma open source di virtualizzazione QEMU-KVM, oggi alla base di sistemi cloud-based come Openstack. Nel primo capitolo, viene effettuato uno studio dello stato dell’arte del Cloud Computing, dei suoi attuali limiti e delle prospettive offerte da un modello di Cloud Federation nel futuro immediato. Nel secondo capitolo vengono discusse nel dettaglio le tecniche di live migration, di recente riferimento per la comunità scientifica internazionale e le possibili ottimizzazioni in scenari inter e intra data center, con l’intento di definire la base teorica per lo studio approfondito dell’implementazione effettiva del processo di migrazione su piattaforma QEMU-KVM, che viene affrontato nel terzo capitolo. In particolare, in quest’ultimo sono descritti i principi architetturali e di funzionamento dell'hypervisor e viene definito il modello di progettazione e l’algoritmo alla base del processo di migrazione. Nel quarto capitolo, infine, si presenta il lavoro svolto, le scelte configurative e progettuali per la creazione di un ambiente di testbed adatto allo studio di sessioni di live migration concorrenti e vengono discussi i risultati delle misure di performance e del comportamento del sistema, tramite le sperimentazioni effettuate.

Analisi delle prestazioni di un codice di calcolo open-source per l'elaborazione dati GNSS in modalità cinematica finalizzata al monitoraggio di strutture e applicazione di filtri sequenziali

Il presente lavoro di tesi si pone come obbiettivo l’elaborazione di dati GNSS in modalità cinematica post-processing per il monitoraggio strutturale e, in una seconda fase, lo studio delle precisioni raggiungibili delle soluzioni ottenute utilizzando algoritmi di post-elaborazione del dato. L’oggetto di studio è la torre Garisenda, situata in piazza Ravegnana, accanto alla torre Asinelli, nel centro storico di Bologna, da tempo oggetto di studi e monitoraggi per via della sua inclinazione particolarmente critica. Per lo studio è stato utilizzato un data set di quindici giorni, dal 15/12/2013 al 29/12/2013 compresi. Per l’elaborazione dei dati è stato utilizzato un software open source realizzato da ricercatori del Politecnico di Milano, goGPS. Quest'ultimo, essendo un codice nuovo, è stato necessario testarlo al fine di poter ottenere dei risultati validi. Nella prima fase della tesi si è quindi affrontato l’aspetto della calibrazione dei parametri che forniscono le soluzioni più precise per le finalità di monitoraggio considerando le possibili scelte offerte dal codice goGPS. In particolare sono stati imposti dei movimenti calibrati e si è osservata la soluzione al variare dei parametri selezionati scegliendo poi quella migliore, ossia il miglior compromesso tra la capacità di individuare i movimenti e il rumore della serie. Nella seconda fase, allo scopo di poter migliorare le precisioni delle soluzioni si sono valutati metodi di correzione delle soluzioni basati sull'uso di filtri sequenziali e sono state condotte analisi sull'incremento di precisione derivante dall'applicazione di tali correzioni.

Detrusor activity is impaired during thoracic epidural analgesia after open renal surgery

There are no data on lower urinary tract function during postoperative thoracic epidural analgesia (TEA). Because selected segmental blockade can be achieved with epidural analgesia, we hypothesized that lower urinary tract function remains unchanged during TEA within segments T4-T11 after open renal surgery.

Toward optimal display of physiologic status in critical care: I. Recreating bedside displays from archived physiologic data

BACKGROUND: Physiologic data display is essential to decision making in critical care. Current displays echo first-generation hemodynamic monitors dating to the 1970s and have not kept pace with new insights into physiology or the needs of clinicians who must make progressively more complex decisions about their patients. The effectiveness of any redesign must be tested before deployment. Tools that compare current displays with novel presentations of processed physiologic data are required. Regenerating conventional physiologic displays from archived physiologic data is an essential first step. OBJECTIVES: The purposes of the study were to (1) describe the SSSI (single sensor single indicator) paradigm that is currently used for physiologic signal displays, (2) identify and discuss possible extensions and enhancements of the SSSI paradigm, and (3) develop a general approach and a software prototype to construct such "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator (MWA) framework-a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA) scripts aimed to create dynamic visualizations (eg, video files in AVI format) of patient vital signs recorded from bedside (intensive care unit or operating room) monitors. Multi Wave Animator creates animations in which vital signs are displayed to mimic their appearance on current bedside monitors. The source code of MWA is freely available online together with a detailed tutorial and sample data sets.

Mobile phone technologies and advanced data analysis towards the enhancement of diabetes self-management

Advances in the area of mobile and wireless communication for healthcare (m-Health) along with the improvements in information science allow the design and development of new patient-centric models for the provision of personalised healthcare services, increase of patient independence and improvement of patient's self-control and self-management capabilities. This paper comprises a brief overview of the m-Health applications towards the self-management of individuals with diabetes mellitus and the enhancement of their quality of life. Furthermore, the design and development of a mobile phone application for Type 1 Diabetes Mellitus (T1DM) self-management is presented. The technical evaluation of the application, which permits the management of blood glucose measurements, blood pressure measurements, insulin dosage, food/drink intake and physical activity, has shown that the use of the mobile phone technologies along with data analysis methods might improve the self-management of T1DM.

Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development

Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database. 48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit.

Investigation of a unique short open reading frame within the 3' untranslated region of the canine distemper virus matrix messenger RNA

Increasing evidence suggest that the long "untranslated" region (UTR) between the matrix (M) and the fusion (F) proteins of morbilliviruses has a functional role. In canine distemper virus (CDV), the F 5' UTR was recently shown to code for a long F signal peptide (Fsp). Subsequently, it was reported that the M/F UTRs combined with the long Fsp were synergistically regulating the F mRNA and protein expression, thereby modulating virulence. Unique to CDV, a short putative open reading frame (ORF) has been identified within the wild-type CDV-M 3' UTR (termed M2). Here, we investigated whether M2 was expressed from the genome of the virulent and demyelinating A75/17-CDV strain. An expression plasmid encoding the M2 ORF tagged both at its N-terminal (HA) and C-terminal domains (RFP), was first constructed. Then, a recombinant virus with its putative M2 ORF replaced by HA-M2-RFP was successfully recovered from cDNA (termed recA75/17(green)-HA-M2-RFP). M2 expression in cells transfected or infected with these mutants was studied by immunoprecipitation, immunofluorescence, immunoblot and flow cytometry analyses. Although fluorescence was readily detected in HA-M2-RFP-transfected cells, absence of red fluorescence emission in several recA75/17(green)-HA-M2-RFP-infected cell types suggested lack of M2 biosynthesis, which was confirmed by the other techniques. Consistent with these data, no functional role of the short polypeptide was revealed by infecting various cell types with HA-M2-RFP over-expressing or M2-knockout recombinant viruses. Thus, in sharp contrast to the CDV-F 5' UTR reported to translate a long Fsp, our data provided evidence that the CDV-M 3' UTR does not express any polypeptides.

Activated coagulation during open and endovascular abdominal aortic aneurysm repair

OBJECTIVE: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR). METHODS: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected. RESULTS: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution. CONCLUSION: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

Determination of histopathological tumor grade in neuroepithelial brain tumors by using spectral pattern analysis of in vivo spectroscopic data

OBJECT: In this study, 1H magnetic resonance (MR) spectroscopy was prospectively tested as a reliable method for presurgical grading of neuroepithelial brain tumors. METHODS: Using a database of tumor spectra obtained in patients with histologically confirmed diagnoses, 94 consecutive untreated patients were studied using single-voxel 1H spectroscopy (point-resolved spectroscopy; TE 135 msec, TE 135 msec, TR 1500 msec). A total of 90 tumor spectra obtained in patients with diagnostic 1H MR spectroscopy examinations were analyzed using commercially available software (MRUI/VARPRO) and classified using linear discriminant analysis as World Health Organization (WHO) Grade I/II, WHO Grade III, or WHO Grade IV lesions. In all cases, the classification results were matched with histopathological diagnoses that were made according to the WHO classification criteria after serial stereotactic biopsy procedures or open surgery. Histopathological studies revealed 30 Grade I/II tumors, 29 Grade III tumors, and 31 Grade IV tumors. The reliability of the histological diagnoses was validated considering a minimum postsurgical follow-up period of 12 months (range 12-37 months). Classifications based on spectroscopic data yielded 31 tumors in Grade I/II, 32 in Grade III, and 27 in Grade IV. Incorrect classifications included two Grade II tumors, one of which was identified as Grade III and one as Grade IV; two Grade III tumors identified as Grade II; two Grade III lesions identified as Grade IV; and six Grade IV tumors identified as Grade III. Furthermore, one glioblastoma (WHO Grade IV) was classified as WHO Grade I/II. This represents an overall success rate of 86%, and a 95% success rate in differentiating low-grade from high-grade tumors. CONCLUSIONS: The authors conclude that in vivo 1H MR spectroscopy is a reliable technique for grading neuroepithelial brain tumors.

Change in pain severity with open label venlafaxine use in patients with a depressive symptomatology: an observational study in primary care

PURPOSE: Venlafaxine has shown benefit in the treatment of depression and pain. Worldwide data are extensively lacking investigating the outcome of chronic pain patients with depressive symptoms treated by venlafaxine in the primary care setting. This observational study aimed to elucidate the efficacy of venlafaxine and its prescription by Swiss primary care physicians and psychiatrists in patients with chronic pain and depressive symptomatology. SUBJECTS AND METHODS: We studied 505 patients with depressive symptoms suffering from chronic pain in a prospective naturalistic Swiss community based observational trial with venlafaxine in primary care. These patients have been treated with venlafaxine by 122 physicians, namely psychiatrists, general practitioners, and internists. RESULTS: On average, patients were treated with 143+/-75 mg (0-450 mg) venlafaxine daily for a follow-up of three months. Venlafaxine proved to be beneficial in the treatment of both depressive symptoms and chronic pain. DISCUSSION: Although side effects were absent in most patients, physicians might have frequently omitted satisfactory response rate of depression by underdosing venlafaxine. Our results reflect the complexity in the treatment of chronic pain in patients with depressive symptoms in primary care. CONCLUSION: Further randomized dose-finding studies are needed to learn more about the appropriate dosage in treating depression and comorbid pain with venlafaxine.

The exchange of radiotherapy data as part of an electronic patient-referral system

PURPOSE: To describe the implementation and use of an electronic patient-referral system as an aid to the efficient referral of patients to a remote and specialized treatment center. METHODS AND MATERIALS: A system for the exchange of radiotherapy data between different commercial planning systems and a specially developed planning system for proton therapy has been developed through the use of the PAPYRUS diagnostic image standard as an intermediate format. To ensure the cooperation of the different TPS manufacturers, the number of data sets defined for transfer has been restricted to the three core data sets of CT, VOIs, and three-dimensional dose distributions. As a complement to the exchange of data, network-wide application-sharing (video-conferencing) technologies have been adopted to provide methods for the interactive discussion and assessment of treatments plans with one or more partner clinics. RESULTS: Through the use of evaluation plans based on the exchanged data, referring clinics can accurately assess the advantages offered by proton therapy on a patient-by-patient basis, while the practicality or otherwise of the proposed treatments can simultaneously be assessed by the proton therapy center. Such a system, along with the interactive capabilities provided by video-conferencing methods, has been found to be an efficient solution to the problem of patient assessment and selection at a specialized treatment center, and is a necessary first step toward the full electronic integration of such centers with their remotely situated referral centers.

Estimation of scots pine defoliation by the common pine sawfly (Diprion pini L.) using multi-temporal radar data

In 1998-2001 Finland suffered the most severe insect outbreak ever recorded, over 500,000 hectares. The outbreak was caused by the common pine sawfly (Diprion pini L.). The outbreak has continued in the study area, Palokangas, ever since. To find a good method to monitor this type of outbreaks, the purpose of this study was to examine the efficacy of multi-temporal ERS-2 and ENVISAT SAR imagery for estimating Scots pine (Pinus sylvestris L.) defoliation. Three methods were tested: unsupervised k-means clustering, supervised linear discriminant analysis (LDA) and logistic regression. In addition, I assessed if harvested areas could be differentiated from the defoliated forest using the same methods. Two different speckle filters were used to determine the effect of filtering on the SAR imagery and subsequent results. The logistic regression performed best, producing a classification accuracy of 81.6% (kappa 0.62) with two classes (no defoliation, >20% defoliation). LDA accuracy was with two classes at best 77.7% (kappa 0.54) and k-means 72.8 (0.46). In general, the largest speckle filter, 5 x 5 image window, performed best. When additional classes were added the accuracy was usually degraded on a step-by-step basis. The results were good, but because of the restrictions in the study they should be confirmed with independent data, before full conclusions can be made that results are reliable. The restrictions include the small size field data and, thus, the problems with accuracy assessment (no separate testing data) as well as the lack of meteorological data from the imaging dates.