LP-OPTIMA: A Framework for Prescriptive Maintenance and Optimization of IoT Resources for Low-Power Embedded Systems.

Low-power embedded systems have been widely used in a variety of applications, allowing devices to efficiently collect and exchange data while minimizing energy consumption. However, the lack of extensive maintenance procedures designed specifically for low-power systems, coupled with constraints on anticipating faults and monitoring capacities, presents notable difficulties and intricacies in identifying failures and customized reaction mechanisms. The proposed approach seeks to address the gaps in current resource management frameworks and maintenance protocols for low-power embedded systems. Furthermore, this paper offers a trilateral framework that provides periodic prescriptions to stakeholders, a periodic control mechanism for automated actions and messages to prevent breakdowns, and a backup AI malfunction detection module to prevent the system from accessing any stress points. To evaluate the AI malfunction detection module approach, three novel autonomous embedded systems based on different ARM Cortex cores have been specifically designed and developed. Real-life results obtained from the testing of the proposed AI malfunction detection module in the developed embedded systems demonstrated outstanding performance, with metrics consistently exceeding 98%. This affirms the efficacy and reliability of the developed approach in enhancing the fault tolerance and maintenance capabilities of low-power embedded systems.

Data-Driven AI Models within a User-Defined Optimization Objective Function in Cement Production.

This paper explores the energy-intensive cement industry, focusing on a plant in Greece and its mill and kiln unit. The data utilized include manipulated, non-manipulated, and uncontrolled variables. The non-manipulated variables are computed based on the machine learning (ML) models and selected by the minimum value of the normalized root mean square error (NRMSE) across nine (9) methods. In case the distribution of the data displayed in the user interface changes, the user should trigger the retrain of the AI models to ensure their accuracy and robustness. To form the objective function, the expert user should define the desired weight for each manipulated or non-manipulated variable through the user interface (UI), along with its corresponding constraints or target value. The user selects the variables involved in the objective function based on the optimization strategy, and the evaluation is based on the comparison of the optimized and the active value of the objective function. The differential evolution (DE) method optimizes the objective function that is formed by the linear combination of the selected variables. The results indicate that using DE improves the operation of both the cement mill and kiln, yielding a lower objective function value compared to the current values.

DSF Core: Integrated Decision Support for Optimal Scheduling of Lifetime Extension Strategies for Industrial Equipment.

This paper proposes a generic algorithm for industries with degrading and/or failing equipment with significant consequences. Based on the specifications and the real-time status of the production line, the algorithm provides decision support to machinery operators and manufacturers about the appropriate lifetime extension strategies to apply, the optimal time-frame for the implementation of each and the relevant machine components. The relevant recommendations of the algorithm are selected by comparing smartly chosen alternatives after simulation-based life cycle evaluation of Key Performance Indicators (KPIs), considering the short-term and long-term impact of decisions on these economic and environmental KPIs. This algorithm requires various inputs, some of which may be calculated by third-party algorithms, so it may be viewed as the ultimate algorithm of an overall Decision Support Framework (DSF). Thus, it is called "DSF Core". The algorithm was applied successfully to three heterogeneous industrial pilots. The results indicate that compared to the lightest possible corrective strategy application policy, following the optimal preventive strategy application policy proposed by this algorithm can reduce the KPI penalties due to stops (i.e., failures and strategies) and production inefficiency by 30-40%.

Mobile App Interventions for Parkinson's Disease, Multiple Sclerosis and Stroke: A Systematic Literature Review.

Central nervous system diseases (CNSDs) lead to significant disability worldwide. Mobile app interventions have recently shown the potential to facilitate monitoring and medical management of patients with CNSDs. In this direction, the characteristics of the mobile apps used in research studies and their level of clinical effectiveness need to be explored in order to advance the multidisciplinary research required in the field of mobile app interventions for CNSDs. A systematic review of mobile app interventions for three major CNSDs, i.e., Parkinson's disease (PD), multiple sclerosis (MS), and stroke, which impose significant burden on people and health care systems around the globe, is presented. A literature search in the bibliographic databases of PubMed and Scopus was performed. Identified studies were assessed in terms of quality, and synthesized according to target disease, mobile app characteristics, study design and outcomes. Overall, 21 studies were included in the review. A total of 3 studies targeted PD (14%), 4 studies targeted MS (19%), and 14 studies targeted stroke (67%). Most studies presented a weak-to-moderate methodological quality. Study samples were small, with 15 studies (71%) including less than 50 participants, and only 4 studies (19%) reporting a study duration of 6 months or more. The majority of the mobile apps focused on exercise and physical rehabilitation. In total, 16 studies (76%) reported positive outcomes related to physical activity and motor function, cognition, quality of life, and education, whereas 5 studies (24%) clearly reported no difference compared to usual care. Mobile app interventions are promising to improve outcomes concerning patient's physical activity, motor ability, cognition, quality of life and education for patients with PD, MS, and Stroke. However, rigorous studies are required to demonstrate robust evidence of their clinical effectiveness.

Smart Workplaces for older adults: coping 'ethically' with technology pervasiveness.

Pervasive technologies such as Artificial Intelligence, Virtual Reality and the Internet of Things, despite their great potential for improved workability and well-being of older workers, entail wide ethical concerns. Aligned with these considerations we emphasize the need to present from the viewpoint of ethics the risks of personalized ICT solutions that aim to remedy health and support the well-being of the ageing population at workplaces. The ethical boundaries of digital technologies are opaque. The main motivation is to cope with the uncertainties of workplaces' digitization and develop an ethics framework, termed SmartFrameWorK, for personalized health support through ICT tools at workplace environments. SmartFrameWorK is built upon a five-dimensional approach of ethics norms: autonomy, privacy, transparency, trustworthiness and accountability to incite trust in digital workplace technologies. A typology underpins these principles and guides the ethical decision-making process with regard to older worker particular needs, context, data type-related risks and digital tools' use throughout their lifecycle. Risk analysis of pervasive technology use and multimodal data collection, highlighted the imperative for ethically aware practices for older workers' activity and behaviour monitoring. The SmartFrameWorK methodology has been applied in a case study to provide evidence that personalized digital services could elicit trust in users through a well-defined framework. Ethics compliance is a dynamic process from participants' engagement to data management. Defining ethical determinants is pivotal towards building trust and reinforcing better workability and well-being in older workers.

A social robot-based platform for health behavior change toward prevention of childhood obesity.

Childhood obesity is a major public health challenge which is linked with the occurrence of diseases such as diabetes and cancer. The COVID-19 pandemic has forced changes to the lifestyle behaviors of children, thereby making the risk of developing obesity even greater. Novel preventive tools and approaches are required to fight childhood obesity. We present a social robot-based platform which utilizes an interactive motivational strategy in communication with children, collects self-reports through the touch of tangible objects, and processes behavioral data, aiming to: (a) screen and assess the behaviors of children in the dimensions of physical activity, diet, and education, and (b) recommend individualized goals for health behavior change. The platform was integrated through a microservice architecture within a multi-component system targeting childhood obesity prevention. The platform was evaluated in an experimental study with 30 children aged 9-12 years in a real-life school setting, showing children's acceptance to use it, and an 80% success rate in achieving weekly personal health goals recommended by the social robot-based platform. The results provide preliminary evidence on the implementation feasibility and potential of the social robot-based platform toward the betterment of children's health behaviors in the context of childhood obesity prevention. Further rigorous longer-term studies are required.

RiskRadar: development and pilot results of a technical intervention targeting combination prevention regarding HIV, viral hepatitis, sexually transmitted infections and tuberculosis.

BACKGROUND: The HIV pandemic impacts the lives of millions and despite the global coordinated response, innovative actions are still needed to end it. A major challenge is the added burden of coinfections such as viral hepatitis, tuberculosis and various sexually transmitted infections in terms of prevention, treatment and increased morbidity in individuals with HIV infection. A need for combination prevention strategies, tailored to high-risk key populations arises and technology-based interventions can be a valuable asset. The COVID-19 pandemic challenged the delivery of existing services and added stress to existing public health and clinical structures but also highlighted the potential of exploiting technical solutions for interventions regarding infectious diseases. In this paper we report the design process, results and evaluation findings from the pilots of 'RiskRadar'-a web and mobile application aiming to support combination prevention, testing and linkage to care for HIV, viral hepatitis, various sexually transmitted infections and tuberculosis. METHODS: RiskRadar was developed for the INTEGRATE Joint Action's aim to improve, adapt and pilot innovative digital tools for combination prevention. RiskRadar was designed iteratively using informed end-user-oriented approaches. Emphasis was placed on the Risk Calculator that enables users to assess their risk of exposure to one or more of the four disease areas, make informed decisions to seek testing or care and adjust their behaviours ultimately aiming to harm/risk reduction. RiskRadar has been piloted in three countries, namely Croatia, Italy and Lithuania. RESULTS: RiskRadar has been used 1347 times across all platforms so far. More than 90% of users have found RiskRadar useful and would use it again, especially the Risk Calculator component. Almost 49.25% are men and 29.85% are in the age group of 25-34. The application has scored 5.2/7 in the User Experience Questionnaire, where it is mainly described as "supportive" and "easy-to-use". The qualitative evaluation of RiskRadar also yielded positive feedback. CONCLUSIONS: Pilot results demonstrate above average satisfaction with RiskRadar and high user-reported usability scores, supporting the idea that technical interventions could significantly support combination prevention actions on Sexually Transmitted Infections.

From a Low-Cost Air Quality Sensor Network to Decision Support Services: Steps towards Data Calibration and Service Development.

Air pollution is a widespread problem due to its impact on both humans and the environment. Providing decision makers with artificial intelligence based solutions requires to monitor the ambient air quality accurately and in a timely manner, as AI models highly depend on the underlying data used to justify the predictions. Unfortunately, in urban contexts, the hyper-locality of air quality, varying from street to street, makes it difficult to monitor using high-end sensors, as the cost of the amount of sensors needed for such local measurements is too high. In addition, development of pollution dispersion models is challenging. The deployment of a low-cost sensor network allows a more dense cover of a region but at the cost of noisier sensing. This paper describes the development and deployment of a low-cost sensor network, discussing its challenges and applications, and is highly motivated by talks with the local municipality and the exploration of new technologies to improve air quality related services. However, before using data from these sources, calibration procedures are needed to ensure that the quality of the data is at a good level. We describe our steps towards developing calibration models and how they benefit the applications identified as important in the talks with the municipality.

Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations.

The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Value of pre-existent bacterial colonization in patients with advanced/relapsed ovarian neoplasms undergoing cytoreductive surgery: a multicenter observational study (BONSAI).

OBJECTIVE: As an increasing number of patients with advanced/relapsed ovarian cancer need extensive cytoreductive procedures, there is an increasing number of complex cases collected in accredited tertiary cancer centers. With nosocomial infections and bacterial colonizations being a significant challenge in these patient cohorts, we aimed to evaluate the risk such infections pose to surgical outcome. METHODS: Prospective assessment of pathological bacterial colonization (vaginal, umbilical/groin, intraperitoneal, urine, oral/nose cavity) in patients who underwent open cytoreductive surgery for advanced/relapsed ovarian cancer in two large European tertiary referral centers for gynecologic malignancies. We recruited patients at initial diagnosis with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian cancer and patients undergoing surgery for relapse. Swabs or cultures were taken from the following sites: vagina, groin and/or umbilicus, urine, intraperitoneal, mouth and/or nose. Only evidence of pathogenic bacteria was considered positive for bacterial colonization. RESULTS: A total of 172 primary advanced (70.9%) or relapsed (29.1%) ovarian cancer patients were included; 63.4% of them had received chemotherapy±additional targeted agents (16.3%) by the time of cytoreduction. 39.5% of the patients had a long-term vascular access line in situ. A bowel resection was performed in 44.8% and a splenectomy in 16.3% of the patients. Predefined surgical morbidity and mortality were 22.3% and 0%, respectively. Forty-one patients (23.8%) screened positive for pathogenic bacterial colonization with the presence of long-term intravenous access as the only independent risk factor identified (OR 2.34; 95% CI 1.05 to 5.34; p=0.04). Type of systemic treatments, previous bowel resections, previous hospitalizations, and patient demographics did not appear to significantly impact the risk of bacterial colonization. Furthermore, pathogenic bacterial colonization was shown to have no significant effect on peri-operative infection-related complications such as abscesses, wound infection, pneumonia, relaparotomy, or anastomotic leak. CONCLUSIONS: A total of 24% of patients undergoing cytoreductive surgery for ovarian cancer were confirmed positive for pathogenic bacterial colonization. The presence of long-term intravenous access was identified as the only significant risk factor for that, however the presence of pathogenic bacterial colonization per se did not seem to adversely affect outcome of cytoreductive effort or increase perioperative infection related complications.

Using a Virtual Reality Serious Game to Assess the Performance of Older Adults with Frailty.

OBJECTIVES: The comparison of cognitive performance of older adults with frailty and non-frail ones (according to Fried's criteria) was investigated. METHODS/DESIGN: The differences in performance between people with frailty and individuals without frailty according to Fried were tested using a Virtual Reality (VR) application. The Fried criteria for frailty were used to categorize users into study groups, while standardized batteries were used for a Comprehensive Geriatric Assessment, including Activities of Daily Living (ADL), lifestyle, cognition, and depression screening. A group of 80 elders (78.08 years old in average) played the VR game entitled Virtual Supermarket (VSM). From those, 39 were healthy controls and 30 were categorized as pre-frail and 11 as frail. The VSM application presented users with a virtual shopping experience where users had to locate and purchase items displayed in a shopping list. This application was designed to test player's ability to reproduce a typical customer behavior in a simulated environment which requires spatial orientation, short-term memory, selective attention, and cognition speed. The performance, duration, and error rate were used as measurements. RESULTS: The analysis showed that there was a statistically significant difference in game performance between the different user groups with X2 (2) = 9.929, p = 0.007. Moreover, the multinomial logistic regression model generated, which based on game performance metrics, was found to be statistically significant with X2 (4) = 15.662, p = 0.004. CONCLUSIONS: Results shed more light toward the possible use of VR for distant self-administered evaluation of the frail status.

COVID-19 Mobile Apps: A Systematic Review of the Literature.

BACKGROUND: A vast amount of mobile apps have been developed during the past few months in an attempt to "flatten the curve" of the increasing number of COVID-19 cases. OBJECTIVE: This systematic review aims to shed light into studies found in the scientific literature that have used and evaluated mobile apps for the prevention, management, treatment, or follow-up of COVID-19. METHODS: We searched the bibliographic databases Global Literature on Coronavirus Disease, PubMed, and Scopus to identify papers focusing on mobile apps for COVID-19 that show evidence of their real-life use and have been developed involving clinical professionals in their design or validation. RESULTS: Mobile apps have been implemented for training, information sharing, risk assessment, self-management of symptoms, contact tracing, home monitoring, and decision making, rapidly offering effective and usable tools for managing the COVID-19 pandemic. CONCLUSIONS: Mobile apps are considered to be a valuable tool for citizens, health professionals, and decision makers in facing critical challenges imposed by the pandemic, such as reducing the burden on hospitals, providing access to credible information, tracking the symptoms and mental health of individuals, and discovering new predictors.

Real-Time Abnormal Event Detection for Enhanced Security in Autonomous Shuttles Mobility Infrastructures.

Autonomous vehicles (AVs) are already operating on the streets of many countries around the globe. Contemporary concerns about AVs do not relate to the implementation of fundamental technologies, as they are already in use, but are rather increasingly centered on the way that such technologies will affect emerging transportation systems, our social environment, and the people living inside it. Many concerns also focus on whether such systems should be fully automated or still be partially controlled by humans. This work aims to address the new reality that is formed in autonomous shuttles mobility infrastructures as a result of the absence of the bus driver and the increased threat from terrorism in European cities. Typically, drivers are trained to handle incidents of passengers' abnormal behavior, incidents of petty crimes, and other abnormal events, according to standard procedures adopted by the transport operator. Surveillance using camera sensors as well as smart software in the bus will maximize the feeling and the actual level of security. In this paper, an online, end-to-end solution is introduced based on deep learning techniques for the timely, accurate, robust, and automatic detection of various petty crime types. The proposed system can identify abnormal passenger behavior such as vandalism and accidents but can also enhance passenger security via petty crimes detection such as aggression, bag-snatching, and vandalism. The solution achieves excellent results across different use cases and environmental conditions.

The European cross-border health data exchange roadmap: Case study in the Italian setting.

Health data exchange is a major challenge due to the sensitive information and the privacy issues entailed. Considering the European context, in which health data must be exchanged between different European Union (EU) Member States, each having a different national regulatory framework as well as different national healthcare structures, the challenge appears even greater. Europe has tried to address this challenge via the epSOS ("Smart Open Services for European Patients") project in 2008, a European large-scale pilot on cross-border sharing of specific health data and services. The adoption of the framework is an ongoing activity, with most Member States planning its implementation by 2020. Yet, this framework is quite generic and leaves a wide space to each EU Member State regarding the definition of roles, processes, workflows and especially the specific integration with the National Infrastructures for eHealth. The aim of this paper is to present the current landscape of the evolving eHealth infrastructure for cross-border health data exchange in Europe, as a result of past and ongoing initiatives, and illustrate challenges, open issues and limitations through a specific case study describing how Italy is approaching its adoption and accommodates the identified barriers. To this end, the paper discusses ethical, regulatory and organizational issues, also focusing on technical aspects, such as interoperability and cybersecurity. Regarding cybersecurity aspects per se, we present the approach of the KONFIDO EU-funded project, which aims to reinforce trust and security in European cross-border health data exchange by leveraging novel approaches and cutting-edge technologies, such as homomorphic encryption, photonic Physical Unclonable Functions (p-PUF), a Security Information and Event Management (SIEM) system, and blockchain-based auditing. In particular, we explain how KONFIDO will test its outcomes through a dedicated pilot based on a realistic scenario, in which Italy is involved in health data exchange with other European countries.

A Low-Cost Indoor Activity Monitoring System for Detecting Frailty in Older Adults.

Indoor localization systems have already wide applications mainly for providing localized information and directions. The majority of them focus on commercial applications providing information such us advertisements, guidance and asset tracking. Medical oriented localization systems are uncommon. Given the fact that an individual's indoor movements can be indicative of his/her clinical status, in this paper we present a low-cost indoor localization system with room-level accuracy used to assess the frailty of older people. We focused on designing a system with easy installation and low cost to be used by non technical staff. The system was installed in older people houses in order to collect data about their indoor localization habits. The collected data were examined in combination with their frailty status, showing a correlation between them. The indoor localization system is based on the processing of Received Signal Strength Indicator (RSSI) measurements by a tracking device, from Bluetooth Beacons, using a fingerprint-based procedure. The system has been tested in realistic settings achieving accuracy above 93% in room estimation. The proposed system was used in 271 houses collecting data for 1⁻7-day sessions. The evaluation of the collected data using ten-fold cross-validation showed an accuracy of 83% in the classification of a monitored person regarding his/her frailty status (Frail, Pre-frail, Non-frail).

Deep Learning on Multi Sensor Data for Counter UAV Applications-A Systematic Review.

Usage of Unmanned Aerial Vehicles (UAVs) is growing rapidly in a wide range of consumer applications, as they prove to be both autonomous and flexible in a variety of environments and tasks. However, this versatility and ease of use also brings a rapid evolution of threats by malicious actors that can use UAVs for criminal activities, converting them to passive or active threats. The need to protect critical infrastructures and important events from such threats has brought advances in counter UAV (c-UAV) applications. Nowadays, c-UAV applications offer systems that comprise a multi-sensory arsenal often including electro-optical, thermal, acoustic, radar and radio frequency sensors, whose information can be fused to increase the confidence of threat's identification. Nevertheless, real-time surveillance is a cumbersome process, but it is absolutely essential to detect promptly the occurrence of adverse events or conditions. To that end, many challenging tasks arise such as object detection, classification, multi-object tracking and multi-sensor information fusion. In recent years, researchers have utilized deep learning based methodologies to tackle these tasks for generic objects and made noteworthy progress, yet applying deep learning for UAV detection and classification is considered a novel concept. Therefore, the need to present a complete overview of deep learning technologies applied to c-UAV related tasks on multi-sensor data has emerged. The aim of this paper is to describe deep learning advances on c-UAV related tasks when applied to data originating from many different sensors as well as multi-sensor information fusion. This survey may help in making recommendations and improvements of c-UAV applications for the future.

Automated shape-based clustering of 3D immunoglobulin protein structures in chronic lymphocytic leukemia.

BACKGROUND: Although the etiology of chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, is still unclear, strong evidence implicates antigen involvement in disease ontogeny and evolution. Primary and 3D structure analysis has been utilised in order to discover indications of antigenic pressure. The latter has been mostly based on the 3D models of the clonotypic B cell receptor immunoglobulin (BcR IG) amino acid sequences. Therefore, their accuracy is directly dependent on the quality of the model construction algorithms and the specific methods used to compare the ensuing models. Thus far, reliable and robust methods that can group the IG 3D models based on their structural characteristics are missing. RESULTS: Here we propose a novel method for clustering a set of proteins based on their 3D structure focusing on 3D structures of BcR IG from a large series of patients with CLL. The method combines techniques from the areas of bioinformatics, 3D object recognition and machine learning. The clustering procedure is based on the extraction of 3D descriptors, encoding various properties of the local and global geometrical structure of the proteins. The descriptors are extracted from aligned pairs of proteins. A combination of individual 3D descriptors is also used as an additional method. The comparison of the automatically generated clusters to manual annotation by experts shows an increased accuracy when using the 3D descriptors compared to plain bioinformatics-based comparison. The accuracy is increased even more when using the combination of 3D descriptors. CONCLUSIONS: The experimental results verify that the use of 3D descriptors commonly used for 3D object recognition can be effectively applied to distinguishing structural differences of proteins. The proposed approach can be applied to provide hints for the existence of structural groups in a large set of unannotated BcR IG protein files in both CLL and, by logical extension, other contexts where it is relevant to characterize BcR IG structural similarity. The method does not present any limitations in application and can be extended to other types of proteins.

Comprehensive user requirements engineering methodology for secure and interoperable health data exchange.

BACKGROUND: Increased digitalization of healthcare comes along with the cost of cybercrime proliferation. This results to patients' and healthcare providers' skepticism to adopt Health Information Technologies (HIT). In Europe, this shortcoming hampers efficient cross-border health data exchange, which requires a holistic, secure and interoperable framework. This study aimed to provide the foundations for designing a secure and interoperable toolkit for cross-border health data exchange within the European Union (EU), conducted in the scope of the KONFIDO project. Particularly, we present our user requirements engineering methodology and the obtained results, driving the technical design of the KONFIDO toolkit. METHODS: Our methodology relied on four pillars: (a) a gap analysis study, reviewing a range of relevant projects/initiatives, technologies as well as cybersecurity strategies for HIT interoperability and cybersecurity; (b) the definition of user scenarios with major focus on cross-border health data exchange in the three pilot countries of the project; (c) a user requirements elicitation phase containing a threat analysis of the business processes entailed in the user scenarios, and (d) surveying and discussing with key stakeholders, aiming to validate the obtained outcomes and identify barriers and facilitators for HIT adoption linked with cybersecurity and interoperability. RESULTS: According to the gap analysis outcomes, full adherence with information security standards is currently not universally met. Sustainability plans shall be defined for adapting existing/evolving frameworks to the state-of-the-art. Overall, lack of integration in a holistic security approach was clearly identified. For each user scenario, we concluded with a comprehensive workflow, highlighting challenges and open issues for their application in our pilot sites. The threat analysis resulted in a set of 30 user goals in total, documented in detail. Finally, indicative barriers of HIT acceptance include lack of awareness regarding HIT risks and legislations, lack of a security-oriented culture and management commitment, as well as usability constraints, while important facilitators concern the adoption of standards and current efforts for a common EU legislation framework. CONCLUSIONS: Our study provides important insights to address secure and interoperable health data exchange, while our methodological framework constitutes a paradigm for investigating diverse cybersecurity-related risks in the health sector.

Chronic Lymphocytic Leukemia Patient Clustering Based on Somatic Hypermutation (SHM) Analysis.

Somatic Hypermutation (SHM) load in the immunoglobulin heavy variable (IGHV) gene of the clonotypic B cell receptor immunoglobulin (BcR IG) is one of the most important prognostic markers in CLL, segregating patients into two distinct categories, with contrariwise disease course. Over the last years, immunogenetic studies have identified that ∼30% of CLL patients carry (quasi)identical BcR IG and thus can be assigned to different subsets with distinct clinicobiological profiles. This characterization was achieved by applying rules mainly concerning the diversity of the VH complementarity determining region 3 (CDR3). Following, studies have also identified subset-specific somatic hypermutation further highlighting antigen selection in disease ontogeny and evolution. In this study, an innovative attempt to explore possible associations amongst SHMs in different CLL patients is implemented and also the potential correlations with VH CDR3 stereotypy is examined, leading to a new classification algorithm implicating both SHM and CDR3 patterns. All results are classified to a ground level analysis, focusing on the most frequent SHMs, their paired associated amino acid changes and the formation of subgroups sharing the same VH CDR3 pattern, the latter being used as a similarity metric. In addition, all results are compared to established VH CDR3 patterns of the well-known CLL subsets in order to confirm the validity of our findings.

Substance deposition assessment in obstructed pulmonary system through numerical characterization of airflow and inhaled particles attributes.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are considered as the two most widespread obstructive lung diseases, whereas they affect more than 500 million people worldwide. Unfortunately, the requirement for detailed geometric models of the lungs in combination with the increased computational resources needed for the simulation of the breathing did not allow great progress to be made in the past for the better understanding of inflammatory diseases of the airways through detailed modelling approaches. In this context, computational fluid dynamics (CFD) simulations accompanied by fluid particle tracing (FPT) analysis of the inhaled ambient particles are deemed critical for lung function assessment. Also they enable the understanding of particle depositions on the airways of patients, since these accumulations may affect or lead to inflammations. In this direction, the current study conducts an initial investigation for the better comprehension of particle deposition within the lungs. More specifically, accurate models of the airways obstructions that relate to pulmonary disease are developed and a thorough assessment of the airflow behavior together with identification of the effects of inhaled particle properties, such as size and density, is conducted. Our approach presents a first step towards an effective personalization of pulmonary treatment in regards to the geometric characteristics of the lungs and the in depth understanding of airflows within the airways. METHODS: A geometry processing technique involving contraction algorithms is established and used to employ the different respiratory arrangements associated with lung related diseases that exhibit airways obstructions. Apart from the normal lung case, two categories of obstructed cases are examined, i.e. models with obstructions in both lungs and models with narrowings in the right lung only. Precise assumptions regarding airflow and deposition fraction (DF) over various sections of the lungs are drawn by simulating these distinct incidents through the finite volume method (FVM) and particularly the CFD and FPT algorithms. Moreover, a detailed parametric analysis clarifies the effects of the particles size and density in terms of regional deposition upon several parts of the pulmonary system. In this manner, the deposition pattern of various substances can be assessed. RESULTS: For the specific case of the unobstructed lung model most particles are detected on the right lung (48.56% of total, when the air flowrate is 12.6 L/min), a fact that is also true when obstructions arise symmetrically in both lungs (51.45% of total, when the air flowrate is 6.06 L/min and obstructions occur after the second generation). In contrast, when narrowings are developed on the right lung only, most particles are pushed on the left section (68.22% of total, when the air flowrate is 11.2 L/min) indicating that inhaled medication is generally deposited away from the areas of inflammation. This observation is useful when designing medical treatment of lung diseases. Furthermore, particles with diameters from 1 µm to 10 µm are shown to be mainly deposited on the lower airways, whereas particles with diameters of 20 µm and 30 µm are mostly accumulated in the upper airways. As a result, the current analysis indicates increased DF levels in the upper airways when the particle diameter is enlarged. Additionally, when the particles density increases from 1000 Kg/m3 to 2000 Kg/m3, the DF is enhanced on every generation and for all cases investigated herein. The results obtained by our simulations provide an accurate and quantitative estimation of all important parameters involved in lung modeling. CONCLUSIONS: The treatment of respiratory diseases with inhaled medical substances can be advanced by the clinical use of accurate CFD and FPT simulations and specifically by evaluating the deposition of inhaled particles in a regional oriented perspective in regards to different particle sizes and particle densities. Since a drug with specific characteristics (i.e. particle size and density) exhibits maximum deposition on particular lung areas, the current study provides initial indications to a qualified physician for proper selection of medication.