Proof Of Concept Case Study Research Articles

Relationship between transcranial magnetic stimulation markers of motor control and clinical recovery in obsessive compulsive disorder/Gilles de la Tourette syndrome: a proof of concept case study.

Obsessive compulsive disorder (OCD) and Gilles de la Tourette syndrome (GTS) are neurodevelopmental disorders characterized by difficulties in controlling intrusive thoughts (obsessions) and undesired actions (tics), respectively. Both conditions have been associated with abnormal inhibition but a tangible deficit of inhibitory control abilities is controversial in GTS. Here, we examined a 25 years-old male patient with severe OCD symptoms and a mild form of GTS, where impairments in motor control were central. Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) to elicit motor-evoked potentials (MEPs) during four experimental sessions, allowing us to assess the excitability of motor intracortical circuitry at rest as well as the degree of MEP suppression during action preparation, a phenomenon thought to regulate movement initiation. When tested for the first time, the patient presented a decent level of MEP suppression during action preparation, but he exhibited a lack of intracortical inhibition at rest, as evidenced by reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI). Interestingly, the patient's symptomatology drastically improved over the course of the sessions (reduced obsessions and tics), coinciding with feedback given on his good motor control abilities. These changes were reflected in the TMS measurements, with a significant strengthening of intracortical inhibition (SICI and LICI more pronounced than previously) and a more selective tuning of MEPs during action preparation; MEPs became even more suppressed, or selectively facilitated depending on the behavioral condition in which they we probed. This study highlights the importance of better understanding motor inhibitory mechanisms in neurodevelopmental disorders and suggests a biofeedback approach as a potential novel treatment.

Assessment of pulmonary fibrosis using weighted gene co-expression network analysis.

For many industrial chemicals toxicological data is sparse regarding several regulatory endpoints, so there is a high and often unmet demand for NAMs that allow for screening and prioritization of these chemicals. In this proof of concept case study we propose multi-gene biomarkers of compounds' ability to induce lung fibrosis and demonstrate their application in vitro. For deriving these biomarkers we used weighted gene co-expression network analysis to reanalyze a study where the time-dependent pulmonary gene-expression in mice treated with bleomycin had been documented. We identified eight modules of 58 to 273 genes each which were particularly activated during the different phases (inflammatory; acute and late fibrotic) of the developing fibrosis. The modules' relation to lung fibrosis was substantiated by comparison to known markers of lung fibrosis from DisGenet. Finally, we show the modules' application as biomarkers of chemical inducers of lung fibrosis based on an in vitro study of four diketones. Clear differences could be found between the lung fibrosis inducing diketones and other compounds with regard to their tendency to induce dose-dependent increases of module activation as determined using a previously proposed differential activation score and the fraction of differentially expressed genes in the modules. Accordingly, this study highlights the potential use of composite biomarkers mechanistic screening for compound-induced lung fibrosis.

Antibiotic-free vaginal microbiota transplant with donor engraftment, dysbiosis resolution and live birth after recurrent pregnancy loss: a proof of concept case study.

Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the traditional treatment, recently combined with local probiotics in some cases. Vaginal Microbiota Transplantation (VMT) with eubiotic vaginal bacterial microbiota after antibiotic eradication of pathogens has successfully been performed in a case study with five patients, but no VMT has been performed without the use of antibiotics. This is a proof of concept case study. The patient was found to have vaginal dysbiosis at the RPL clinic at Copenhagen University Hospital Hvidovre, Denmark on the 23rd of June 2021. She was offered and accepted to receive experimental treatment in the form of a VMT as a compassionate use case. VMT is the transfer of cervicovaginal secretions (CVS) from a healthy donor with a Lactobacillus-dominant vaginal microbiome to a recipient with a dysbiotic vaginal microbiome. CVS is a mixture of e.g., mucus, bacteria, metabolites present in the vaginal canal. Potential donors were thoroughly screened for the absence of STIs, and the most suitable donor sample for the specific patient in this study was determined via an invitro microbiome competition assay. A 30-year-old patient with one livebirth and a complicated pregnancy history of two stillbirths and 1s trimester pregnancy loss in gestational weeks 27 (2019), 17 (2020) and 23 (2020) respectively with complaints of vaginal irritation and discharge that had aggravated in all her pregnancies. Her vaginal microbiome composition showed a 90% dominance of Gardnerella spp. After one VMT there was a complete shift in microbiome composition to 81.2% L.crispatus and 9% L.jensenii with a concurrent resolvement of vaginal symptoms. Single nucleotide polymorphism-analysis confirmed her microbiome to be of donor origin and it remain stable now 1.5 years after the VMT. Five months after the VMT she became pregnant and has successfully delivered a healthy baby at term. Here we report a successful VMT with confirmed donor strain engraftment followed by a successful pregnancy and delivery after a series of late pregnancy losses/stillbirths. Findings suggest that VMT is a potential treatment for severe vaginal dysbiosis. Further, larger studies are required. The study was partially funded (i.e., analysis costs) by Freya Biosciences Aps, Fruebjergvej, 2100 Copenhagen, Denmark.

Suitability of magnetic microbolometers based on paramagnetic temperature sensors for CMB polarization measurements

High resolution maps of polarization anisotropies of the Cosmic Microwave Background (CMB) are in high demand, since the discovery of primordial B-Modes in the polarization patterns would confirm the inflationary phase of the Universe that would have taken place before the last scattering of the CMB at the recombination epoch. Transition Edge Sensors (TES) and Microwave Kinetic Inductance Detectors (MKID) are the predominant detector technologies of cryogenic detector array based CMB instruments that search for primordial B-Modes. In this paper we propose another type of cryogenic detector to be used for CMB survey: A magnetic microbolometer (MMB) that is based on a paramagnetic temperature sensor. It is an adaption of state-of-the-art metallic magnetic calorimeters (MMCs) that are meanwhile a key technology for high resolution $\alpha$, $\beta$, $\gamma$ and X-ray spectroscopy as well as the study of neutrino mass. The effort to adapt MMCs for CMB surveys is triggered by their lack of Johnson noise associated with the detector readout, the possibility of straightforward calibration and higher dynamic range given it possesses a broad and smooth responsivity dependence with temperature and the absence of Joule dissipation which simplifies the thermal design. A brief proof of concept case study is analyzed, taking into account typical constraints in CMB measurements and reliable microfabrication processes. The results show that MMBs provide a promising technology for CMB polarization survey as their sensitivity can be tuned for background limited detection of the sky while simultaneously maintaining a low time response to avoid distortion of the point-source response of the telescope. As the sensor technology and its fabrication techniques are compatible with TES based bolometric detector arrays, a change of detector technology would even come with very low cost.

Feature importance measures to dissect the role of sub-basins in shaping the catchment hydrological response: a proof of concept

Understanding the response of a catchment is a crucial problem in hydrology, with a variety of practical and theoretical implications. Dissecting the role of sub-basins is helpful both for advancing current knowledge of physical processes and for improving the implementation of simulation or forecast models. In this context, recent advancements in sensitivity analysis tools could be worthwhile for bringing out hidden dynamics otherwise not easy to distinguish in complex data driven investigations. In the present work seven feature importance measures are described and tested in a specific and simplified proof of concept case study. In practice, simulated runoff time series are generated for a watershed and its inner 15 sub-basins. A machine learning tool is calibrated using the sub-basins time series for forecasting the watershed runoff. Importance measures are applied on such synthetic hydrological scenario with the aim to investigate the role of each sub-basin in shaping the overall catchment response. This proof of concept offers a simplified representation of the complex dynamics of catchment response. The interesting result is that the discharge at the catchment outlet depends mainly on 3 sub-basins that are consistently identified by alternative sensitivity measures. The proposed approach can be extended to real applications, providing useful insights on the role of each sub-basin also analyzing more complex scenarios.

Combining Neuromodulation Strategies to Improve Locomotor Function in SCI: A Proof of Concept Case Study

<h3>Research Objectives</h3> Acute intermittent hypoxia (AIH) and transcutaneous spinal cord stimulation (tSCS) are two non-invasive neuromodulation treatments that have been shown to individually induce spinal plasticity in persons with chronic incomplete spinal cord injury (iSCI). However, these two interventions have never been tested in combination to see if their combined effect is greater than each intervention alone. This proof of concept case study investigated how AIH combined with tSCS during ambulation training may facilitate improvements in walking function in individuals with iSCI. <h3>Design</h3> Single-blind, randomized, crossover trial. <h3>Setting</h3> Outpatient, Rehabilitation Hospital. <h3>Participants</h3> 1 participant (male, 70 years) with chronic iSCI. <h3>Interventions</h3> The participant completed 3 arms, in random order: 1. AIH+tSCS 2. Sham-AIH+Sham-tSCS 3. Sham-AIH+tSCS Each arm consisted of 5 treatment sessions on consecutive days. <h3>Main Outcome Measures</h3> Assessments were performed at Baseline, Post-intervention (Post), and 1-week follow-up (1WFU), with a 4-week wash out between arms. Changes in gait performance were measured using the 10-meter walk test (10MWT) for fast and comfortable speeds, and the 6-minute walk test (6MWT). <h3>Results</h3> Overall, the participant showed potential improvements in his walking performance with AIH+tSCS at Post, relative to Baseline (10MWT-Fast: 5.6%; 10MWT-Comfortable: 7.0%; 6MWT: 15.6%), with further improvements at 1WFU (10MWT-Fast: 6.9%; 10MWT-Comfortable: 19.2%; 6MWT: 19.3%). The participant also showed potential improvements at Post, relative to Baseline with Sham-AIH+Sham-tSCS (10MWT-Fast: 12.2%; 10MWT-Comfortable: 6.6%; 6MWT: 15.1%) and with Sham-AIH+tSCS (10MWT-Fast: -2.5%; 10MWT-Comfortable: 15.3%; 6MWT: 6.0%). However, sustained improvements were not present at 1WFU with the Sham-AIH+Sham-tSCS (10MWT-Fast: 3.8%; 10MWT-Comfortable: -2.5%; 6MWT: 8.3%) or Sham-AIH+tSCS (10MWT-Fast: -3.9%; 10MWT-Comfortable: -5.5%; 6MWT: -2.1%), suggesting the combined intervention yielded retention effects. <h3>Conclusions</h3> AIH +tSCS with gait training may promote persistent improvements in walking function compared to tSCS with gait training or gait training alone in persons with iSCI. Further studies are warranted to investigate this novel, combinational neuromodulation strategy. <h3>Author(s) Disclosures</h3> The authors have no conflicts of interest to disclose.

Integrating publicly available information to screen potential candidates for chemical prioritization under the Toxic Substances Control Act: A proof of concept case study using genotoxicity and carcinogenicity

The Toxic Substances Control Act (TSCA) became law in the U.S. in 1976 and was amended in 2016. The amended law requires the U.S. EPA to perform risk-based evaluations of existing chemicals. Here, we developed a tiered approach to screen potential candidates based on their genotoxicity and carcinogenicity information to inform the selection of candidate chemicals for prioritization under TSCA. The approach was underpinned by a large database of carcinogenicity and genotoxicity information that had been compiled from various public sources. Carcinogenicity data included weight-of-evidence human carcinogenicity evaluations and animal cancer data. Genotoxicity data included bacterial gene mutation data from the Salmonella (Ames) and Escherichia coli WP2 assays and chromosomal mutation (clastogenicity) data. Additionally, Ames and clastogenicity outcomes were predicted using the alert schemes within the OECD QSAR Toolbox and the Toxicity Estimation Software Tool (TEST).The evaluation workflows for carcinogenicity and genotoxicity were developed along with associated scoring schemes to make an overall outcome determination. For this case study, two sets of chemicals, the TSCA Active Inventory non-confidential portion list available on the EPA CompTox Chemicals Dashboard (33,364 chemicals, ‘TSCA Active List’) and a representative proof-of-concept (POC) set of 238 chemicals were profiled through the two workflows to make determinations of carcinogenicity and genotoxicity potential. Of the 33,364 substances on the ‘TSCA Active List’, overall calls could be made for 20,371 substances. Here 46.67%% (9507) of substances were non-genotoxic, 0.5% (103) were scored as inconclusive, 43.93% (8949) were predicted genotoxic and 8.9% (1812) were genotoxic. Overall calls for genotoxicity could be made for 225 of the 238 POC chemicals. Of these, 40.44% (91) were non-genotoxic, 2.67% (6) were inconclusive, 6.22% (14) were predicted genotoxic, and 50.67% (114) genotoxic. The approach shows promise as a means to identify potential candidates for prioritization from a genotoxicity and carcinogenicity perspective.

Matrix Trays: From waste to opportunities

Matrix Trays are single-use plastic carriers used to transport integrated chips and circuit board components during automated test and assembly processes for Printed Circuit Boards. These trays represent a significant yet consistent waste stream; primarily in the electronics industry and many other industries that integrate microchips into their products especially the automotive industry. By the end of 2017, the National Sword Policy which was implemented by China on plastic waste import from other countries and especially the United States catalyzed a huge crisis and forced manufacturers and companies to deal with their own plastic waste streams. This study presents two alternative approaches of reusing trays to the reduced conventional recycling practices which have caused used trays to remain in storage or be deposited in landfills. Approaches including a students’ design competition and a proof of concept case study for an autonomous shading device are presented. The shading device was designed, tested and validated. Trays were transformed from waste into 13 possible products showing that a circular economy and industrial symbiosis can be achieved by integrating multidisciplinary reuse approaches for by-product reuse and sustainable industry practices. Environmental and economic impacts were evaluated comparing reuse to recycling, combustion and landfilling. The results showed that reusing trays reduces energy consumption and greenhouse gas emissions.

Morphodynamic modelling of dryland non-perennial riverscapes, with implications for environmental water allocation

Reach-scale river restoration or environmental water allocation (EWA) exercises typically address the magnitude and temporal dynamics (frequency, duration, timing, rate of change) of flows required to sustain desirable ecological conditions along a river. The role of geomorphology in this process is to broaden the gaze beyond flows to consider larger and longer-term interactions between valley lithological structure, and the feed and fate of flow-sediment mixtures. This paper proposes the integration of numerical morphodynamic modelling in evaluations of environmental water requirements for non-perennial riverscapes (channel–riparian–floodplain environments). The paper presents a methodological framework, and proof of concept case study from the Touws River, South Africa, for the application of morphodynamic modelling in EWA. The paper illustrates operational approaches to modelling the complexity of dryland mixed bedrock-alluvial (and mixed-load) riverscapes with highly variable non-perennial flow regimes, including an approach to generating initial bed conditions for numerical experiments by ‘morphodynamic spin-up’, and approaches to synthesising and presenting numerical experiment output in the form of a dynamic range of potential variability in metrics of physical habitat suitability and diversity, and disturbance/renewal regimes. Such efforts can assist in enhancing field observations and testing field-based hypotheses of flow-sediment regime–physical habitat associations, extending the timescales of analysis beyond field observation, and constraining uncertainty about the dynamic range of variability in responses to predicted future flow-sediment regime modifications. Further research is needed to develop growth models appropriate for key non-perennial river vegetation types, to support biomorphodynamic modelling of geomorphology–vegetation interactions, and to determine or predict appropriate inlet sediment concentrations for historical and future modification scenarios.

Accuracy of movement quality screening to document effects of neuromuscular control retraining exercises in a young ex-footballer with hip and groin symptoms: A proof of concept case study

Hip and groin pain is common in footballers and altering movement patterns can reduce symptoms. Observational tests of movement control are thought to identify abnormal movement patterns, but their accuracy needs yet to be confirmed by comparison with an objective measure. To assess the accuracy, using 3D motion analysis, of observational movement control tests and their ability to detect changes, and document changes in symptoms following a neuromuscular control exercise programme in an ex-footballer with hip and groin pain. A 25-year-old male with chronic bilateral hip and groin pain had their movement control ability rated and kinematic data collected using 3D motion analysis while performing Small Knee Bend (SKB) and SKB with Rotation (SKB Rot) tests pre-and post-neuromuscular control exercise training. Movement control was rated as at fault if they were unable to control specific trunk and pelvic movements during the tests. The Copenhagen Hip and Groin Outcome Score (HAGOS) was used to assess symptoms. Following the intervention, observational rating during the SKB test improved from fault to no fault for anterior pelvic tilt, which decreased by 17° and 16° during right and left leg SKB tests respectively. The HAGOS symptoms subsection improved from 36% to 61%. Observational movement screening ratings were supported by 3-D motion analysis. These findings indicate that the screening tool was accurate for detecting improvements in trunk and pelvic movement control following an exercise programme in an ex-footballer who had presented with hip and groin pain.

A specific two-pulse release of rivastigmine using a modified time-controlled delivery system: A proof of concept case study

Currently, the orally administrated rivastigmine is based on twice daily formulations which also demand a titration process in order to increase the tolerability of the drug. In the present study an attempt was made to design and prepare an innovative single unit, once daily, double pulse release formulation for oral administration of rivastigmine in order to increase patient compliance without causing tolerance development. The pulsatile system was prepared as a tablet-in-tablet using a compression-coating method. An in-vitro dissolution test was utilized to determine the release profile of the drug from this system. The results showed that the designed delivery system provided two consecutive pulses of rivastigmine with a time difference of 6.5 h between the peaks of the pulses. The outer tablet provided an immediate release which lasted up to 4 h. The inner tablet, on the other hand, which was a film coated tablet, presented a capability of time-controlled delivery which was manifested by a lag time of 3 h followed by a burst release. The lag time was dependent, to a considerable extent, on the film coating weight. Surprisingly, the compression-coating did not alter the release features of the inner tablet whatsoever.

Combining frontal gamma asymmetry neurofeedback with virtual reality: A proof of concept case study

The current proof of concept case study was designed to determine if a consumer-grade neurofeedback system (Muse) could be used in conjunction with specially designed VR environments (Positivity by Healium) to impact gamma frontal asymmetry as well as create positive changes in mood states. Four firefighters served as subjects and completed pre-post mood rating scales as well as 19-channel EEG recordings. An examination of sLORETA frontal lobe ROI’s demonstrated a post-intervention gamma asymmetry shift to the left in 3 of the 4 subjects. In addition, subjects generally reported changes in mood consistent with the frontal asymmetry changes. Overall, these results provide initial support for the idea that a consumer grade BCI/VR intervention can potentially have therapeutic utility and deserve further study.

Data-driven Urban Energy Simulation (DUE-S): A framework for integrating engineering simulation and machine learning methods in a multi-scale urban energy modeling workflow

The world is rapidly urbanizing, and the energy intensive built environment is becoming increasingly responsible for the world’s energy consumption and associated environmental emissions. As a result, significant efforts have been put forth to develop methods that can accurately model and characterize building energy consumption in cities. These models aim to utilize physics-based building energy simulations, reduced-order calculations and statistical learning methods to assess the energy performance of buildings within a dense urban area. However, current urban building energy models are limited in their ability to account for the inter-building energy dynamics and urban microclimate factors that can have a substantial impact on building energy use. To overcome these limitations, this paper proposes a novel Data-driven Urban Energy Simulation (DUE-S) framework that integrates a network-based machine learning algorithm (ResNet) with engineering simulation to better understand how buildings consume energy on multiple temporal (hourly, daily, monthly) and spatial scales in a city (single building, block, urban). We validate the proposed DUE-S framework on a proof of concept case study of 22 densely located university buildings in California, USA. Our results indicate that the DUE-S framework is able to accurately predict urban scale energy consumption at hourly, daily and monthly intervals. Moreover, our results also demonstrate that the integration of data-driven and engineering simulation approaches can partially capture the inter-building energy dynamics and impacts of the urban context and merits future work to explore how they can be improved to predict sub-urban scale energy predictions (single building, block). In the end, successfully predicting and modeling the energy performance of urban buildings has the potential to inform the decision-making of a wide variety of urban sustainability stakeholders including architects, engineers and policymakers.

A key agreement protocol with partial backward confidentiality

The essence of dynamic group key agreement protocols is to help compute a secure key for a group communication with a dynamic set of participants in distributed systems. In dynamic group key agreement protocols, the number of participants may change over time because of participants leaving or joining the group. The security of such join and leave operations are affected by the existence of backward confidentiality and forward confidentiality, respectively. Dynamic group key agreement protocols are expected to be used in applications such as file sharing systems. However, there are a number of problems in the use of existing dynamic group key agreement protocols in file sharing systems such as lack of privacy, violation of availability and dependency for key escrow. In this study, we propose a new security property called partial backward confidentiality. Partial backward confidentiality is the property, in which a new participant can compute the last valid group key just before joining the group but the new participant cannot compute former group keys. Moreover, we propose a key agreement protocol to show the provision of partial backward confidentiality that helps to solve file sharing system problems above. Furthermore, we have analyzed the security of the proposed protocol with respect to impersonation attacks under the difficulty in discrete logarithm problem and eavesdropping under the Decisional Difie-Hellman Problem. We present a proof of concept case study called Private File Sharing System in order to show the applicability of partial backward confidentiality property.

Detecting variation of emotions in online activities

Abstract Online text sources form evolving large scale data repositories out of which valuable knowledge about human emotions can be derived. Beyond the primary emotions which refer to the global emotional signals, deeper understanding of a wider spectrum of emotions is important to detect online public views and attitudes. The present work is motivated by the need to test and provide a system that categorizes emotion in online activities. Such a system can be beneficial for online services, companies recommendations, and social support communities. The main contributions of this work are to: (a) detect primary emotions, social ones, and those that characterize general affective states from online text sources, (b) compare and validate different emotional analysis processes to highlight those that are most efficient, and (c) provide a proof of concept case study to monitor and validate online activity, both explicitly and implicitly. The proposed approaches are tested on three datasets collected from different sources, i.e., news agencies, Twitter, and Facebook, and on different languages, i.e., English and Greek. Study results demonstrate that the methodologies at hand succeed to detect a wider spectrum of emotions out of text sources.

Breakthrough capability for UVOIR space astronomy: Reaching the darkest sky

We describe how availability of new solar electric propulsion (SEP) technology can substantially increase the science capability of space astronomy missions working within the near-UV to far-infrared (UVOIR) spectrum by making dark sky orbits accessible for the first time. We present a proof of concept case study in which SEP is used to enable a 700kg Explorer-class observatory payload to reach an orbit beyond where the zodiacal dust limits observatory sensitivity. The resulting scientific performance advantage relative to a Sun–Earth L2 point orbit is presented and discussed. We find that making SEP available to astrophysics Explorers can enable this small payload program to rival the science performance of much larger long development-time systems. We also present flight dynamics analysis which illustrates that this concept can be extended beyond Explorers to substantially improve the sensitivity performance of heavier (7000kg) flagship-class astrophysics payloads such as the UVOIR successor to the James Webb Space Telescope by using high power SEP that is being developed for the Asteroid Redirect Robotics Mission.

Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics.

Intravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this proof of concept case-study we tested: (i) whether interferon-alfa (IFN)-free treatment with SIL plus ribavirin (RBV) can achieve sustained virological response (SVR); (ii) whether SIL is safe and feasible for prolonged duration of treatment and (iii) whether mathematical modelling of early on-treatment HCV kinetics can guide duration of therapy to achieve SVR. A 44 year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200 mg/day of SIL, 1200 mg/day of RBV and 6000 u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1-12 weeks until the end of therapy. The standard biphasic mathematical model with time-varying SIL effectiveness was used to predict the duration of therapy to achieve SVR. Based on modelling the observed viral kinetics during the first 3 weeks of treatment, SVR was predicted to be achieved within 34 weeks of therapy. Provided with this information, the patient agreed to complete 34 weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe and achieved SVR (week-33). We report, for the first time, the use of real-time mathematical modelling of HCV kinetics to individualize duration of IFN-free therapy and to empower a patient to participate in shared decision making regarding length of treatment. SIL-based individualized therapy provides a treatment option for patients who do not respond to or cannot receive other HCV agents and should be further validated.

A Framework for Developing Context-aware Systems

In ubiquitous computing the environment constraints are often regarded as static and software applications are allowed to function in a mobile ecospace. However, in context-aware systems the environment attributes of software applications are dynamically changing. This dynamism of contexts must be accounted for in order to provide the true intended effect on the application of services. Consequently, context-aware software applications should perceive their context in a continuous manner and seamlessly adapt to it. This thesis investigates the process of constructing context-aware applications and identifies the main challenges in this domain. The two principal requirements are (1) formally defining what context is and expressing the enclosed semantics, (2) formally defining dynamic compositions of adaptations and triggering their responses to changes in the environment context. This thesis proposes a component-based architecture for a Context-aware Framework that would be used to bring awareness capabilities into applications. Two languages are formally designed. One is to formally express situations, leading to a context reasoner, and another is to formally express workflow, leading to timely triggering of reactions and enforcing policies. With these formalisms and a component design that can be formalized, the thesis work fulfills a formal approach to construct context-aware applications. A proof-ofconcept case study is implemented to examine the expressiveness of the framework design and test its implementation.

Stepping to the Beat Improves Spatiotemporal Characteristics of Gait in Stroke Patients with Hemiparesis: A Proof of Concept Case Study of a Home-based Training Intervention

Hemiparetic gait due to stroke is characterized by temporal asymmetry and variability. Research shows this can be improved by auditory cueing, whereby participants train to step in time and space with a visual or auditory cue. This particular method is effective in training a symmetrical gait and helps to improve coordination and speed. We describe a pilot study that investigates the possibility of training with an auditory rhythmical metronome embedded in music, during stepping in place within a home- based setting. Stepping in place incorporates aspects of movements that are also important for a successful gait, such as reciprocal flexion and extension of the legs in timely coordination and synchronization, creating a step frequency, a swing phase and single limb support. Stepping in place may also provide a valuable method for home-based training, as little space in the home is required and, therefore, participants are less likely to fall. This case study seeks to obtain proof of the concept that stepping in place within a home setting may be a useful tool for locomotor training after stroke.A hemiparetic stroke patient, PF, successfully completed 6 weeks of home-based training for 15minutes a day, 5 days a week (with 5% weekly increments in music tempo). PF (aged 58) is a male, right handed, chronic stroke survivor, who presented left sided hemiparesis. He was recruited from a local stroke club based on the inclusion criteria that he was able to walk independently without supervision (but able to use a gait aid such as a cane or walker) and was free from hearing impairments. Finally, PF was also able to complete a 3 m Timed Up and Go, which is typically used as an indicator of falls and provides an indication of the patient's ability during turns. He was assessed five times during the 12 week period of the study, which included baseline, three weeks of training, three weeks of rest (used to measure resting effects), a second three-week training period and finally after another three weeks of rest. During each assessment, PF was tested for his gait speed during a 10 m walking task. During these tests, we also captured the spatiotemporal parameters of his gait using six accelerometer sensors (OPAL, APDM). The sensors were placed around the trunk, the lumbar, and the left and right shins and feet and have been designed to measure walking. The use of such motion capture systems is intended to provide a more sensitive and objective measure of the changes in movement that might occur following gait rehabilitation, compared to the use of standard clinical measures. We also used the following clinical assessments: The Dynamic Gait Index (which measures balance during walking), and The Rivermead Motor Scale (measuring general walking ability).The results showed significant improvements in all spatiotemporal aspects of PF's gait. There was a 10 s speed increase in his 10 m walking, between his baseline and final assessment. Furthermore, changes in PF's gait cycle were shown after 6 weeks of training stepping in place, suggesting improvements towards a more symmetrical gait pattern. For example, an increase in cadence was revealed, which likely follows increases in the gait speed during 10 m walking. A decrease in the overall gait cycle time, decreases in double support, and further decreases in stride length asymmetry and swing asymmetry were also observed. These findings might be expected based on previous work investigating changes in spatiotemporal parameters after gait rehabilitation and suggest that training stepping in place generalizes to walking ability. Furthermore, no changes were observed in any of the clinical assessments, suggesting the need for more sensitive measures of functional ability in capturing improvements of lower limb function after training stepping in place. These preliminary data show promising results for stepping in place in the home, as a method of training a symmetrical gait after stroke. This method also provides a cheap addition to other rehabilitation techniques such as physiotherapy, as it can be conducted within the home, without the need for a therapist and will provide patients with more intensive rehabilitation after stroke. Lastly, it is important to note, based on patient feedback that presenting the rhythmical beat in a music context was likely a key factor in motivating the patient to complete his training. As compliance is of high importance in rehabilitation, incorporating music should be taken into consideration for future investigations whereby the training provided may be repetitive in nature.

Secure embedded system hardware design – A flexible security and trust enhanced approach

Embedded systems have found a very strong foothold in global Information Technology (IT) market since they can provide very specialized and intricate functionality to a wide range of products. On the other hand, the migration of IT functionality to a plethora of new smart devices (like mobile phones, cars, aviation, game or households machines) has enabled the collection of a considerable number of data that can be characterized sensitive. Therefore, there is a need for protecting that data through IT security means. However, eare usually dployed in hostile environments where they can be easily subject of physical attacks. In this paper, we provide an overview from ES hardware perspective of methods and mechanisms for providing strong security and trust. The various categories of physical attacks on security related embedded systems are presented along with countermeasures to thwart them and the importance of reconfigurable logic flexibility, adaptability and scalability along with trust protection mechanisms is highlighted. We adopt those mechanisms in order to propose a FPGA based embedded system hardware architecture capable of providing security and trust along with physical attack protection using trust zone separation. The benefits of such approach are discussed and a subsystem of the proposed architecture is implemented in FPGA technology as a proof of concept case study. From the performed analysis and implementation, it is concluded that flexibility, security and trust are fully realistic options for embedded system security enhancement.