Toward a 3D in vitro model based on decellularized thymus to maintain adult thymic ephitelial cells functionality

During my PhD,I have been develop an innovative technique to reproduce in vitro the 3D thymic microenvironment, to be used for growth and differentiation of thymocytes, and possible transplantation replacement in conditions of depressed thymic immune regulation. The work has been developed in the laboratory of Tissue Engineering at the University Hospital in Basel, Switzerland, under the tutorship of Prof.Ivan Martin. Since a number of studies have suggested that the 3D structure of the thymic microenvironment might play a key role in regulating the survival and functional competence of thymocytes, I’ve focused my effort on the isolation and purification of the extracellular matrix of the mouse thymus. Specifically, based on the assumption that TEC can favour the differentiation of pre-T lymphocytes, I’ve developed a specific decellularization protocol to obtain the intact, DNA-free extracellular matrix of the adult mouse thymus. Two different protocols satisfied the main characteristics of a decellularized matrix, according to qualitative and quantitative assays. In particular, the quantity of DNA was less than 10% in absolute value, no positive staining for cells was found and the 3D structure and composition of the ECM were maintained. In addition, I was able to prove that the decellularized matrixes were not cytotoxic for the cells themselves, and were able to increase expression of MHC II antigens compared to control cells grown in standard conditions. I was able to prove that TECs grow and proliferate up to ten days on top the decellularized matrix. After a complete characterization of the culture system, these innovative natural scaffolds could be used to improve the standard culture conditions of TEC, to study in vitro the action of different factors on their differentiation genes, and to test the ability of TECs to induce in vitro maturation of seeded T lymphocytes.

Biomechanical model of human cornea based on stromal microstructure

The optical characteristics of the human cornea depends on the mechanical balance between the intra-ocular pressure and intrinsic tissue stiffness. A wide range of ophthalmic surgical procedures alter corneal biomechanics to induce local or global curvature changes for the correction of visual acuity. Due to the large number of surgical interventions performed every day, a deeper understanding of corneal biomechanics is needed to improve the safety of these procedures and medical devices. The aim of this study is to propose a biomechanical model of the human cornea, based on stromal microstructure. The constitutive mechanical law includes collagen fiber distribution based on X-ray scattering analysis, collagen cross-linking, and fiber uncrimping. Our results showed that the proposed model reproduced inflation and extensiometry experimental data [Elsheikh et al., Curr. Eye Res., 2007; Elsheikh et al., Exp. Eye Res., 2008] successfully. The mechanical properties obtained for different age groups demonstrated an increase in collagen cross-linking for older specimens. In future work such a model could be used to simulate non-symmetric interventions, and provide better surgical planning.

Two-Dimensional Manganese(II) Coordination Polymer Based on Phthalate and Pyrazine Bridges Exhibiting Antiferromagnetic Porperties

Benzodifuran-functionalised pyrene and anthracene fluorophores 1 and 2 were obtained in reasonable yields. Their single crystal structures, electrochemical, optical absorption, and fluorescence characteristics have been described. They show strong luminescence with high quantum yields of 0.53 for 1 and 0.48 for 2. Magnetic measurements for the 2D coordination polymer [Mn(Pht(Pyz(H2O)2]n (1), in which metal centres are linked together by pyrazine (Pyz) and 1,6-bridging o-phthalate ligand (Pht2-), revealed antiferromagnetic interactions between Mn(II) ions.

Medication errors in a swiss cardiovascular surgery department: a cross-sectional study based on a novel medication error report method

The purpose of this study was (1) to determine frequency and type of medication errors (MEs), (2) to assess the number of MEs prevented by registered nurses, (3) to assess the consequences of ME for patients, and (4) to compare the number of MEs reported by a newly developed medication error self-reporting tool to the number reported by the traditional incident reporting system. We conducted a cross-sectional study on ME in the Cardiovascular Surgery Department of Bern University Hospital in Switzerland. Eligible registered nurses (n = 119) involving in the medication process were included. Data on ME were collected using an investigator-developed medication error self reporting tool (MESRT) that asked about the occurrence and characteristics of ME. Registered nurses were instructed to complete a MESRT at the end of each shift even if there was no ME. All MESRTs were completed anonymously. During the one-month study period, a total of 987 MESRTs were returned. Of the 987 completed MESRTs, 288 (29%) indicated that there had been an ME. Registered nurses reported preventing 49 (5%) MEs. Overall, eight (2.8%) MEs had patient consequences. The high response rate suggests that this new method may be a very effective approach to detect, report, and describe ME in hospitals.

Monte Carlo simulation of a dynamic MLC based on a multiple source model

Detailed knowledge of the characteristics of the radiation field shaped by a multileaf collimator (MLC) is essential in intensity modulated radiotherapy (IMRT). A previously developed multiple source model (MSM) for a 6 MV beam was extended to a 15 MV beam and supplemented with an accurate model of an 80-leaf dynamic MLC. Using the supplemented MSM and the MC code GEANT, lateral dose distributions were calculated in a water phantom and a portal water phantom. A field which is normally used for the validation of the step and shoot technique and a field from a realistic IMRT treatment plan delivered with dynamic MLC are investigated. To assess possible spectral changes caused by the modulation of beam intensity by an MLC, the energy spectra in five portal planes were calculated for moving slits of different widths. The extension of the MSM to 15 MV was validated by analysing energy fluences, depth doses and dose profiles. In addition, the MC-calculated primary energy spectrum was verified with an energy spectrum which was reconstructed from transmission measurements. MC-calculated dose profiles using the MSM for the step and shoot case and for the dynamic MLC case are in very good agreement with the measured data from film dosimetry. The investigation of a 13 cm wide field shows an increase in mean photon energy of up to 16% for the 0.25 cm slit compared to the open beam for 6 MV and of up to 6% for 15 MV, respectively. In conclusion, the MSM supplemented with the dynamic MLC has proven to be a powerful tool for investigational and benchmarking purposes or even for dose calculations in IMRT.

Wireless and passive pressure sensor system based on the magnetic higher-order harmonic field

The goal of this work is to develop a magnetic-based passive and wireless pressure sensor for use in biomedical applications. Structurally, the pressure sensor, referred to as the magneto-harmonic pressure sensor, is composed of two magnetic elements: a magnetically-soft material acts as a sensing element, and a magnetically hard material acts as a biasing element. Both elements are embedded within a rigid sensor body and sealed with an elastomer pressure membrane. Upon excitation of an externally applied AC magnetic field, the sensing element is capable of producing higher-order magnetic signature that is able to be remotely detected with an external receiving coil. When exposed to environment with changing ambient pressure, the elastomer pressure membrane of pressure sensor is deflected depending on the surrounding pressure. The deflection of elastomer membrane changes the separation distance between the sensing and biasing elements. As a result, the higher-order harmonic signal emitted by the magnetically-soft sensing element is shifted, allowing detection of pressure change by determining the extent of the harmonic shifting. The passive and wireless nature of the sensor is enabled with an external excitation and receiving system consisting of an excitation coil and a receiving coil. These unique characteristics made the sensor suitable to be used for continuous and long-term pressure monitoring, particularly useful for biomedical applications which often require frequent surveillance. In this work, abdominal aortic aneurysm is selected as the disease model for evaluation the performance of pressure sensor and system. Animal model, with subcutaneous sensor implantation in mice, was conducted to demonstrate the efficacy and feasibility of pressure sensor in biological environment.

Can decision making in general surgery be based on evidence? An empirical study of Cochrane Reviews

BACKGROUND: This empirical study analyzes the current status of Cochrane Reviews (CRs) and their strength of recommendation for evidence-based decision making in the field of general surgery. METHODS: Systematic literature search of the Cochrane Database of Systematic Reviews and the Cochrane Collaboration's homepage to identify available CRs on surgical topics. Quantitative and qualitative characteristics, utilization, and formulated treatment recommendations were evaluated by 2 independent reviewers. Association of review characteristics with treatment recommendation was analyzed using univariate and multivariate logistic regression models. RESULTS: Ninety-three CRs, including 1,403 primary studies and 246,473 patients, were identified. Mean number of included primary studies per CR was 15.1 (standard deviation [SD] 14.5) including 2,650 (SD 3,340) study patients. Two and a half (SD 8.3) nonrandomized trials were included per analyzed CR. Seventy-two (77%) CRs were published or updated in 2005 or later. Explicit treatment recommendations were given in 45 (48%). Presence of a treatment recommendation was associated with the number of included primary studies and the proportion of randomized studies. Utilization of surgical CRs remained low and showed large inter-country differences. The most surgical CRs were accessed in UK, USA, and Australia, followed by several Western and Eastern European countries. CONCLUSION: Only a minority of available CRs address surgical questions and their current usage is low. Instead of unsystematically increasing the number of surgical CRs it would be far more efficient to focus the review process on relevant surgical questions. Prioritization of CRs needs valid methods which should be developed by the scientific surgical community.

Computer-aided diagnosis of carotid atherosclerosis based on ultrasound image statistics, laws' texture and neural networks

Quantitative characterisation of carotid atherosclerosis and classification into symptomatic or asymptomatic is crucial in planning optimal treatment of atheromatous plaque. The computer-aided diagnosis (CAD) system described in this paper can analyse ultrasound (US) images of carotid artery and classify them into symptomatic or asymptomatic based on their echogenicity characteristics. The CAD system consists of three modules: a) the feature extraction module, where first-order statistical (FOS) features and Laws' texture energy can be estimated, b) the dimensionality reduction module, where the number of features can be reduced using analysis of variance (ANOVA), and c) the classifier module consisting of a neural network (NN) trained by a novel hybrid method based on genetic algorithms (GAs) along with the back propagation algorithm. The hybrid method is able to select the most robust features, to adjust automatically the NN architecture and to optimise the classification performance. The performance is measured by the accuracy, sensitivity, specificity and the area under the receiver-operating characteristic (ROC) curve. The CAD design and development is based on images from 54 symptomatic and 54 asymptomatic plaques. This study demonstrates the ability of a CAD system based on US image analysis and a hybrid trained NN to identify atheromatous plaques at high risk of stroke.

Investigations into Velocity and Distance Perception Based on Different Types of Moving Sound Sources with Respect to Auditory Virtual Environments

The characteristics of moving sound sources have strong implications on the listener's distance perception and the estimation of velocity. Modifications of the typical sound emissions as they are currently occurring due to the tendency towards electromobility have an impact on the pedestrian's safety in road traffic. Thus, investigations of the relevant cues for velocity and distance perception of moving sound sources are not only of interest for the psychoacoustic community, but also for several applications, like e.g. virtual reality, noise pollution and safety aspects of road traffic. This article describes a series of psychoacoustic experiments in this field. Dichotic and diotic stimuli of a set of real-life recordings taken from a passing passenger car and a motorcycle were presented to test subjects who in turn were asked to determine the velocity of the object and its minimal distance from the listener. The results of these psychoacoustic experiments show that the estimated velocity is strongly linked to the object's distance. Furthermore, it could be shown that binaural cues contribute significantly to the perception of velocity. In a further experiment, it was shown that - independently of the type of the vehicle - the main parameter for distance determination is the maximum sound pressure level at the listener's position. The article suggests a system architecture for the adequate consideration of moving sound sources in virtual auditory environments. Virtual environments can thus be used to investigate the influence of new vehicle powertrain concepts and the related sound emissions of these vehicles on the pedestrians' ability to estimate the distance and velocity of moving objects.

Predicting 3-year mortality after percutaneous coronary intervention: updated logistic clinical SYNTAX score based on patient-level data from 7 contemporary stent trials

OBJECTIVES This study aimed to update the Logistic Clinical SYNTAX score to predict 3-year survival after percutaneous coronary intervention (PCI) and compare the performance with the SYNTAX score alone. BACKGROUND The SYNTAX score is a well-established angiographic tool to predict long-term outcomes after PCI. The Logistic Clinical SYNTAX score, developed by combining clinical variables with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX score alone in predicting 1-year outcomes after PCI. However, the ability of this score to predict long-term survival is unknown. METHODS Patient-level data (N = 6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed. We revised the overall risk and the predictor effects in the core model (SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction) using Cox regression analysis to predict mortality at 3 years. We also updated the extended model by combining the core model with additional independent predictors of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and body mass index). RESULTS The revised Logistic Clinical SYNTAX models showed better discriminative ability than the anatomic SYNTAX score for the prediction of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and extended model, 0.73 in a cross-validation procedure). The extended model in particular performed better in differentiating low- and intermediate-risk groups. CONCLUSIONS Risk scores combining clinical characteristics with the anatomic SYNTAX score substantially better predict 3-year mortality than the SYNTAX score alone and should be used for long-term risk stratification of patients undergoing PCI.

Biomechanical validation of computer assisted planning of periacetabular osteotomy: A preliminary study based on finite element analysis

Periacetabular Osteotomy (PAO) is a joint preserving surgical intervention intended to increase femoral head coverage and thereby to improve stability in young patients with hip dysplasia. Previously, we developed a CT-based, computer-assisted program for PAO diagnosis and planning, which allows for quantifying the 3D acetabular morphology with parameters such as acetabular version, inclination, lateral center edge (LCE) angle and femoral head coverage ratio (CO). In order to verify the hypothesis that our morphology-based planning strategy can improve biomechanical characteristics of dysplastic hips, we developed a 3D finite element model based on patient-specific geometry to predict cartilage contact stress change before and after morphology-based planning. Our experimental results demonstrated that the morphology-based planning strategy could reduce cartilage contact pressures and at the same time increase contact areas. In conclusion, our computer-assisted system is an efficient tool for PAO planning.

Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes

Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

Predicting psychotherapy outcome based on therapist interpersonal skills: A five-year longitudinal study of a therapist assessment protocol

Objective: In the past decade, variation in outcomes between therapists (i.e., therapist effects) have become increasingly recognized as an important factor in psychotherapy. Less is known, however, about what accounts for differences between therapists. The present study investigates the possibility that therapists' basic therapy-related interpersonal skills may impact outcomes. Method: To examine this, psychotherapy postgraduate trainees completed both an observer- and an expert-rated behavioral assessment: the Therapy-Related Interpersonal Behaviors (TRIB). TRIB scores were used to predict trainees' outcomes over the course of the subsequent five years. Results: Results indicate that trainees' with more positively rated interpersonal behaviors assessed in the observer-rated group format but not in a single expert-rated format showed superior outcomes over the five-year period. This effect remained controlling for therapist characteristics (therapist gender, theoretical orientation [cognitive behavioral or psychodynamic], amount of supervision, patient's order within therapist's caseload), and patient characteristics (patient age, gender, number of comorbid diagnoses, global severity, and personality disorder diagnosis). Conclusions: These findings underscore the importance of therapists' interpersonal skills as a predictor of outcome and source of therapist effects. The potential utility of assessing therapists' and therapists-in-training interpersonal skills are discussed.

Hydrology dataset based on 111 CTD stations in the North Aegean Sea during June 1998 from the project INTERREGAEGEAN

The combination of two research projects offered us the opportunity to perform a comprehensive study of the seasonal evolution of the hydrological structure and the circulation of the North Aegean Sea, at the northern extremes of the eastern Mediterranean. The combination of brackish water inflow from the Dardanelles and the sea-bottom relief dictate the significant differences between the North and South Aegean water columns. The relatively warm and highly saline South Aegean waters enter the North Aegean through the dominant cyclonic circulation of the basin. In the North Aegean, three layers of distinct water masses of very different properties are observed: The 20-50 m thick surface layer is occupied mainly by Black Sea Water, modified on its way through the Bosphorus, the Sea of Marmara and the Dardanelles. Below the surface layer there is warm and highly saline water originating in the South Aegean and the Levantine, extending down to 350-400 m depth. Below this layer, the deeper-than-400 m basins of the North Aegean contain locally formed, very dense water with different i/S characteristics at each subbasin. The circulation is characterised by a series of permanent, semi-permanent and transient mesoscale features, overlaid on the general slow cyclonic circulation of the Aegean. The mesoscale activity, while not necessarily important in enhancing isopycnal mixing in the region, in combination with the very high stratification of the upper layers, however, increases the residence time of the water of the upper layers in the general area of the North Aegean. As a result, water having out-flowed from the Black Sea in the winter, forms a separate distinct layer in the region in spring (lying between "younger" BSW and the Levantine origin water), and is still traceable in the water column in late summer.