Change mechanisms of schema-centered group psychotherapy with personality disorder patients

Background This study addressed the temporal properties of personality disorders and their treatment by schema-centered group psychotherapy. It investigated the change mechanisms of psychotherapy using a novel method by which psychotherapy can be modeled explicitly in the temporal domain. Methodology and Findings 69 patients were assigned to a specific schema-centered behavioral group psychotherapy, 26 to social skills training as a control condition. The largest diagnostic subgroups were narcissistic and borderline personality disorder. Both treatments offered 30 group sessions of 100 min duration each, at a frequency of two sessions per week. Therapy process was described by components resulting from principal component analysis of patients' session-reports that were obtained after each session. These patient-assessed components were Clarification, Bond, Rejection, and Emotional Activation. The statistical approach focused on time-lagged associations of components using time-series panel analysis. This method provided a detailed quantitative representation of therapy process. It was found that Clarification played a core role in schema-centered psychotherapy, reducing rejection and regulating the emotion of patients. This was also a change mechanism linked to therapy outcome. Conclusions/Significance The introduced process-oriented methodology allowed to highlight the mechanisms by which psychotherapeutic treatment became effective. Additionally, process models depicted the actual patterns that differentiated specific diagnostic subgroups. Time-series analysis explores Granger causality, a non-experimental approximation of causality based on temporal sequences. This methodology, resting upon naturalistic data, can explicate mechanisms of action in psychotherapy research and illustrate the temporal patterns underlying personality disorders.

Authentication and Authorisation Mechanisms in support of Secure Access to WMN Resources

Over the past several years, a number of design approaches in wireless mesh networks have been introduced to support the deployment of wireless mesh networks (WMNs). We introduce a novel wireless mesh architecture that supports authentication and authorisation functionalities, giving the possibility of a seamless WMN integration into the home's organization authentication and authorisation infrastructure. First, we introduce a novel authentication and authorisation mechanism for wireless mesh nodes. The mechanism is designed upon an existing federated access control approach, i.e. the AAI infrastructure that is using just the credentials at the user's home organization in a federation. Second, we demonstrate how authentication and authorisation for end users is implemented by using an existing web-based captive portal approach. Finally, we observe the difference between the two and explain in detail the process flow of authorized access to network resources in wireless mesh networks. The goal of our wireless mesh architecture is to enable easy broadband network access to researchers at remote locations, giving them additional advantage of a secure access to their measurements, irrespective of their location. It also provides an important basis for the real-life deployment of wireless mesh networks for the support of environmental research.

Molecular mechanisms involved in T cell migration across the blood-brain barrier

In the healthy individuum lymphocyte traffic into the central nervous system (CNS) is very low and tightly controlled by the highly specialized blood-brain barrier (BBB). In contrast, under inflammatory conditions of the CNS such as in multiple sclerosis or in its animal model experimental autoimmune encephalomyelitis (EAE) circulating lymphocytes and monocytes/macrophages readily cross the BBB and gain access to the CNS leading to edema, inflammation and demyelination. Interaction of circulating leukocytes with the endothelium of the blood-spinal cord and blood-brain barrier therefore is a critical step in the pathogenesis of inflammatory diseases of the CNS. Leukocyte/endothelial interactions are mediated by adhesion molecules and chemokines and their respective chemokine receptors. We have developed a novel spinal cord window preparation, which enables us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Applying this technique of intravital fluorescence videomicroscopy we could provide direct in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that alpha4-integrin mediates the G-protein independent capture and subsequently the G-protein dependent adhesion strengthening of T cell blasts to microvascular VCAM-1. LFA-1 was found to neither mediate the G-protein independent capture nor the G- protein dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessel, but was rather involved in T cell extravasation across the vascular wall into the spinal cord parenchyme. Our observation that G-protein mediated signalling is required to promote adhesion strengthening of encephalitogenic T cells on BBB endothelium in vivo suggested the involvement of chemokines in this process. We found functional expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in CNS venules surrounded by inflammatory cells in brain and spinal cord sections of mice afflicted with EAE suggesting that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing to secondary lymphoid tissue might be involved in T lymphocyte migration into the immuneprivileged CNS during immunosurveillance and chronic inflammation. Here, I summarize our current knowledge on the sequence of traffic signals involved in T lymphocyte recruitment across the healthy and inflamed blood-brain and blood-spinal cord barrier based on our in vitro and in vivo investigations.

Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients

PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. RESULTS: Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes (P=0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival analysis revealed no significant differences among the genotypes. CONCLUSION: Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.

Mechanisms of airway obliteration after lung transplantation

Post-transplant bronchiolitis obliterans, also called bronchiolitis obliterans syndrome, affects up to 50-60% of patients who survive 5 yr after surgery according to its clinical definition, which is based on the degree of obstructive airway disease. Alloimmune-independent and -dependent mechanisms produce injuries and inflammation of epithelial cells and subepithelial structures, leading to aberrant tissue repair. The triggering of innate immunity by various infections or chemical injuries after, for example, gastroesophageal reflux, may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiation of rejection episodes. These phenomena may be limited in time and location or may be protracted. Reducing the risk of alloimmune-independent factors may be as important as treating acute episodes of lung rejection. Excessive immunosuppression may be deleterious by increasing the risk of infection, thereby triggering innate and adaptive immunity. New potential therapeutic targets are emerging from the research performed on leukotriene receptors, chemokine receptors, and growth factors. Neutralizing these molecules reduces the initial mononuclear and polynuclear infiltrates or the subsequent fibroproliferative process and the neovascular changes, feeding this process.

Soils on the global agenda. Developing international mechanisms for sustainable land management

The objective of the report is to contribute towards developing international mechanisms for SLM. The report provides an overview of international actions concerned with sustainable land management, based on contributions from members of the IASUS (International Actions for the Sustainable Use of Soil) network made at the Eurosoil Symposium. It also aims to concretise possible follow-up actions. On the occasion of the ISRIC workshop “World Soils Issues and Sustainable Development” held on 10 March 2006, the creation of a World Soils Council (WSC) was initiated. The report presents in its final chapter the WSC’s proposed vision, objectives, and structure.

Intracavity Generation of Radially Polarized CO2 Laser Beams Based on a Simple Binary Dielectric Diffraction Grating

We present experimental results on the intracavity generation of radially polarized light by incorporation of a polarization-selective mirror in a CO2 -laser resonator. The selectivity is achieved with a simple binary dielectric diffraction grating etched in the backsurface of the mirror substrate. Very high polarization selectivity was achieved, and good agreement of simulation and experimental results is shown. The overall radial polarization purity of the generated laser beam was found to be higher than 90% .

Dosimetric impact of geometric errors due to respiratory motion prediction on dynamic multileaf collimator-based four-dimensional radiation delivery

The synchronization of dynamic multileaf collimator (DMLC) response with respiratory motion is critical to ensure the accuracy of DMLC-based four dimensional (4D) radiation delivery. In practice, however, a finite time delay (response time) between the acquisition of tumor position and multileaf collimator response necessitates predictive models of respiratory tumor motion to synchronize radiation delivery. Predicting a complex process such as respiratory motion introduces geometric errors, which have been reported in several publications. However, the dosimetric effect of such errors on 4D radiation delivery has not yet been investigated. Thus, our aim in this work was to quantify the dosimetric effects of geometric error due to prediction under several different conditions. Conformal and intensity modulated radiation therapy (IMRT) plans for a lung patient were generated for anterior-posterior/posterior-anterior (AP/PA) beam arrangements at 6 and 18 MV energies to provide planned dose distributions. Respiratory motion data was obtained from 60 diaphragm-motion fluoroscopy recordings from five patients. A linear adaptive filter was employed to predict the tumor position. The geometric error of prediction was defined as the absolute difference between predicted and actual positions at each diaphragm position. Distributions of geometric error of prediction were obtained for all of the respiratory motion data. Planned dose distributions were then convolved with distributions for the geometric error of prediction to obtain convolved dose distributions. The dosimetric effect of such geometric errors was determined as a function of several variables: response time (0-0.6 s), beam energy (6/18 MV), treatment delivery (3D/4D), treatment type (conformal/IMRT), beam direction (AP/PA), and breathing training type (free breathing/audio instruction/visual feedback). Dose difference and distance-to-agreement analysis was employed to quantify results. Based on our data, the dosimetric impact of prediction (a) increased with response time, (b) was larger for 3D radiation therapy as compared with 4D radiation therapy, (c) was relatively insensitive to change in beam energy and beam direction, (d) was greater for IMRT distributions as compared with conformal distributions, (e) was smaller than the dosimetric impact of latency, and (f) was greatest for respiration motion with audio instructions, followed by visual feedback and free breathing. Geometric errors of prediction that occur during 4D radiation delivery introduce dosimetric errors that are dependent on several factors, such as response time, treatment-delivery type, and beam energy. Even for relatively small response times of 0.6 s into the future, dosimetric errors due to prediction could approach delivery errors when respiratory motion is not accounted for at all. To reduce the dosimetric impact, better predictive models and/or shorter response times are required.

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.

Applicability and dosimetric impact of ultrasound-based preplanning in high-dose-rate brachytherapy of prostate cancer

BACKGROUND AND PURPOSE: Analyses of permanent brachytherapy seed implants of the prostate have demonstrated that the use of a preplan may lead to a considerable decrease of dosimetric implant quality. The authors aimed to determine whether the same drawbacks of preplanning also apply to high-dose-rate (HDR) brachytherapy. PATIENTS AND METHODS: 15 patients who underwent two separate HDR brachytherapy implants in addition to external-beam radiation therapy for advanced prostate cancer were analyzed. A pretherapeutic transrectal ultrasound was performed in all patients to generate a preplan for the first brachytherapy implant. For the second brachytherapy, a subset of patients were treated by preplans based on the ultrasound from the first brachytherapy implant. Preplans were compared with the respective postplans assessing the following parameters: coverage index, minimum target dose, homogeneity index, and dose exposure of organs at risk. The prostate geometries (volume, width, height, length) were compared as well. RESULTS: At the first brachytherapy, the matching between the preplan and actual implant geometry was sufficient in 47% of the patients, and the preplan could be applied. The dosimetric implant quality decreased considerably: the mean coverage differed by -0.11, the mean minimum target dose by -0.15, the mean homogeneity index by -0.09. The exposure of organs at risk was not substantially altered. At the second brachytherapy, all patients could be treated by the preplan; the differences between the implant quality parameters were less pronounced. The changes of prostate geometry between preplans and postplans were considerable, the differences in volume ranging from -8.0 to 13.8 cm(3) and in dimensions (width, height, length) from -1.1 to 1.0 cm. CONCLUSION: Preplanning in HDR brachytherapy of the prostate is associated with a substantial decrease of dosimetric implant quality, when the preplan is based on a pretherapeutic ultrasound. The implant quality is less impaired in subsequent implants of fractionated brachytherapy.

Non-photorealistic rendering of virtual implant models for computer-assisted fluoroscopy-based surgical procedures

Surgical navigation systems visualize the positions and orientations of surgical instruments and implants as graphical overlays onto a medical image of the operated anatomy on a computer monitor. The orthopaedic surgical navigation systems could be categorized according to the image modalities that are used for the visualization of surgical action. In the so-called CT-based systems or 'surgeon-defined anatomy' based systems, where a 3D volume or surface representation of the operated anatomy could be constructed from the preoperatively acquired tomographic data or through intraoperatively digitized anatomy landmarks, a photorealistic rendering of the surgical action has been identified to greatly improve usability of these navigation systems. However, this may not hold true when the virtual representation of surgical instruments and implants is superimposed onto 2D projection images in a fluoroscopy-based navigation system due to the so-called image occlusion problem. Image occlusion occurs when the field of view of the fluoroscopic image is occupied by the virtual representation of surgical implants or instruments. In these situations, the surgeon may miss part of the image details, even if transparency and/or wire-frame rendering is used. In this paper, we propose to use non-photorealistic rendering to overcome this difficulty. Laboratory testing results on foamed plastic bones during various computer-assisted fluoroscopybased surgical procedures including total hip arthroplasty and long bone fracture reduction and osteosynthesis are shown.

Photolithography based patterning of bacteriorhodopsin films

The patterning of photoactive purple membrane (PM) films onto electronic substrates to create a biologically based light detection device was investigated. This research is part of a larger collaborative effort to develop a miniaturized toxin detection platform. This platform will utilize PM films containing the photoactive protein bacteriorhodopsin to convert light energy to electrical energy. Following an effort to pattern PM films using focused ion beam machining, the photolithography based bacteriorhodopsin patterning technique (PBBPT) was developed. This technique utilizes conventional photolithography techniques to pattern oriented PM films onto flat substrates. After the basic patterning process was developed, studies were conducted that confirmed the photoelectric functionality of the PM films after patterning. Several process variables were studied and optimized in order to increase the pattern quality of the PM films. Optical microscopy, scanning electron microscopy, and interferometric microscopy were used to evaluate the PM films produced by the patterning technique. Patterned PM films with lateral dimensions of 15 μm have been demonstrated using this technique. Unlike other patterning techniques, the PBBPT uses standard photolithographic processes that make its integration with conventional semiconductor fabrication feasible. The final effort of this research involved integrating PM films patterned using the PBBPT with PMOS transistors. An indirect integration of PM films with PMOS transistors was successfully demonstrated. This indirect integration used the voltage produced by a patterned PM film under light exposure to modulate the gate of a PMOS transistor, activating the transistor. Following this success, a study investigating how this PM based light detection system responded to variations in light intensity supplied to the PM film. This work provides a successful proof of concept for a portion of the toxin detection platform currently under development.

Reducing main memory access latency through SDRAM address mapping techniques and access reordering mechanisms

As the performance gap between microprocessors and memory continues to increase, main memory accesses result in long latencies which become a factor limiting system performance. Previous studies show that main memory access streams contain significant localities and SDRAM devices provide parallelism through multiple banks and channels. These locality and parallelism have not been exploited thoroughly by conventional memory controllers. In this thesis, SDRAM address mapping techniques and memory access reordering mechanisms are studied and applied to memory controller design with the goal of reducing observed main memory access latency. The proposed bit-reversal address mapping attempts to distribute main memory accesses evenly in the SDRAM address space to enable bank parallelism. As memory accesses to unique banks are interleaved, the access latencies are partially hidden and therefore reduced. With the consideration of cache conflict misses, bit-reversal address mapping is able to direct potential row conflicts to different banks, further improving the performance. The proposed burst scheduling is a novel access reordering mechanism, which creates bursts by clustering accesses directed to the same rows of the same banks. Subjected to a threshold, reads are allowed to preempt writes and qualified writes are piggybacked at the end of the bursts. A sophisticated access scheduler selects accesses based on priorities and interleaves accesses to maximize the SDRAM data bus utilization. Consequentially burst scheduling reduces row conflict rate, increasing and exploiting the available row locality. Using a revised SimpleScalar and M5 simulator, both techniques are evaluated and compared with existing academic and industrial solutions. With SPEC CPU2000 benchmarks, bit-reversal reduces the execution time by 14% on average over traditional page interleaving address mapping. Burst scheduling also achieves a 15% reduction in execution time over conventional bank in order scheduling. Working constructively together, bit-reversal and burst scheduling successfully achieve a 19% speedup across simulated benchmarks.

Model based experimental investigation on Powered Gait Orthosis (PGO)

Research on rehabilitation showed that appropriate and repetitive mechanical movements can help spinal cord injured individuals to restore their functional standing and walking. The objective of this paper was to achieve appropriate and repetitive joint movements and approximately normal gait through the PGO by replicating normal walking, and to minimize the energy consumption for both patients and the device. A model based experimental investigative approach is presented in this dissertation. First, a human model was created in Ideas and human walking was simulated in Adams. The main feature of this model was the foot ground contact model, which had distributed contact points along the foot and varied viscoelasticity. The model was validated by comparison of simulated results of normal walking and measured ones from the literature. It was used to simulate current PGO walking to investigate the real causes of poor function of the current PGO, even though it had joint movements close to normal walking. The direct cause was one leg moving at a time, which resulted in short step length and no clearance after toe off. It can not be solved by simply adding power on both hip joints. In order to find a better answer, a PGO mechanism model was used to investigate different walking mechanisms by locking or releasing some joints. A trade-off between energy consumption, control complexity and standing position was found. Finally a foot release PGO virtual model was created and simulated and only foot release mechanism was developed into a prototype. Both the release mechanism and the design of foot release were validated through the experiment by adding the foot release on the current PGO. This demonstrated an advancement in improving functional aspects of the current PGO even without a whole physical model of foot release PGO for comparison.

Fabrication and characterization of room temperature operating single electron transistors using focused ion beam technologies

The single electron transistor (SET) is a Coulomb blockade device, whose operation is based on the controlled manipulation of individual electrons. Single electron transistors show immense potential to be used in future ultra lowpower devices, high density memory and also in high precision electrometry. Most SET devices operate at cryogenic temperatures, because the charging energy is much smaller than the thermal oscillations. The room temperature operation of these devices is possible with sub- 10nm nano-islands due to the inverse dependance of charging energy on the radius of the conducting nano-island. The fabrication of sub-10nm features with existing lithographic techniques is a technological challenge. Here we present the results for the first room temperature operating SET device fabricated using Focused Ion Beam deposition technology. The SET device, incorporates an array of tungsten nano-islands with an average diameter of 8nm. The SET devices shows clear Coulomb blockade for different gate voltages at room temperature. The charging energy of the device was calculated to be 160.0 meV; the capacitance per junction was found to be 0.94 atto F; and the tunnel resistance per junction was calculated to be 1.26 G Ω. The tunnel resistance is five orders of magnitude larger than the quantum of resistance (26 k Ω) and allows for the localization of electrons on the tungsten nano-island. The lower capacitance of the device combined with the high tunnel resistance, allows for the Coulomb blockade effects observed at room temperature. Different device configurations, minimizing the total capacitance of the device have been explored. The effect of the geometry of the nano electrodes on the device characteristics has been presented. Simulated device characteristics, based on the soliton model have been discussed. The first application of SET device as a gas sensor has been demonstrated.