Requirements and Design of a Platform for Internet- and Mobile-based Interventions

Mental health and the therapeutic care of patients is a topic that is applied daily. Whether mental or physical health, usually everyone can complain about something. Due to digitalisation, the topic of mental health must also be raised to a higher level. The eSano system represents a platform that explicitly deals with the concept of e-health in order to provide online support for therapeutic care. The online therapy is provided via so-called Internet- and Mobile-based interventions (IMIs), which are carried out by the patients. The basic principle is that an eCoach accompanies the patient through guided interventions, but the patient also has the possibility to carry out an unguided intervention in a self-guiding manner. As a result of the possibility to perform the interventions on the mobile phone at any time, the use is very flexible, independent of location and can be easily integrated into everyday life. In addition to an application for patients and therapists, there is also a platform for intervention creation and editing, which is the beginning of the development of IMIs for psychological support. In this bachelor thesis the requirements and the conceptual design of the eSano platform are identified and presented. The functional and non-functional requirements to be realized in the final system form the basis of the design concept. Starting with the basic architecture of the platform, creating and participating in interventions and the implementation of individual modules of the therapy, this thesis presents the connection and communication between the systems and roles involved. Furthermore, aspects such as distribution of rights, privacy and security are addressed and basically defined. Due to the realization of a requirements engineering process of the complete eSano system, the results of this thesis form a good basis for any further work with the project

The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms

BACKGROUND: Dystrophins and dystrobrevins are distantly related proteins with important but poorly understood roles in the function of metazoan muscular and neuronal tissues. Defects in them and their associated proteins cause a range of neuromuscular disorders. Members of this superfamily have been discovered in a relatively serendipitous way; we set out to compile a comprehensive description of dystrophin- and dystrobrevin-related sequences from available metazoan genome sequences, validated in representative organisms by RT-PCR, or acquired de novo from key species. RESULTS: Features of the superfamily revealed by our survey include: a) Dystrotelin, an entirely novel branch of the superfamily, present in most vertebrates examined. Dystrotelin is expressed in the central nervous system, and is a possible orthologue of Drosophila DAH. We describe the preliminary characterisation of its function, evolution and expression. b) A novel vertebrate member of the dystrobrevin family, γ-dystrobrevin, an ancient branch now extant only in fish, but probably present in our own ancestors. Like dystrophin, zebrafish γ-dystrobrevin mRNA is localised to myosepta. c) The extent of conservation of alternative splicing and alternative promoter use in the dystrophin and dystrobrevin genes; alternative splicing of dystrophin exons 73 and 78 and α-dystrobrevin exon 13 are conserved across vertebrates, as are the use of the Dp116, Dp71 and G-utrophin promoters; the Dp260 and Dp140 promoters are tetrapod innovations. d) The evolution of the unique N-terminus of DRP2 and its relationship to Dp116 and G-utrophin. e) A C-terminally truncated common ancestor of dystrophin and utrophin in cyclostomes. f) A severely restricted repertoire of dystrophin complex components in ascidians. CONCLUSION: We have refined our understanding of the evolutionary history and isoform diversity of the five previously reported vertebrate superfamily members and describe two novel members, dystrotelin and γ-dystrobrevin. Dystrotelins, dystrophins and dystrobrevins are roughly equally related to each other. Vertebrates therefore have a repertoire of seven superfamily members (three dystrophins, three dystrobevins, and one dystrotelin), with one lost in tetrapods. Most invertebrates studied have one member from each branch. Although the basic shared function which is implied by the common architecture of these distantly related proteins remains unclear, it clearly permeates metazoan biology

Effects of cardiovascular single pill combinations compared with identical multi-pill therapies on healthcare cost and utilization in Germany

Aim: This study assessed whether a single pill combination (SPC) is associated with lower direct healthcare costs. Materials & methods: Anonymized claims data of patients ≥18 years treated with drugs for cardiovascular (CV)-related diseases either as a single pill combination or multi-pill combination (followup to 1 year) were evaluated. After propensity score matching, 59,336 out of 1,369,840 patients were analyzed. Results: In all cohorts, patients receiving a single pill combination had a lower frequency of general practitioner and specialist visits. The patients also had a significantly lower ratio of all-cause hospitalization days and number of CV-related prescriptions as well as all-cause prescriptions (with one exception) compared with those receiving a multi-pill combination. Conclusion: Direct CV-related costs were significantly lower in four out of seven comparisons, with a trend toward lower costs in the other three comparisons

Epigenetic control of alternative mRNA processing at the imprinted Herc3/Nap1l5 locus

Alternative polyadenylation increases transcriptome diversity by generating multiple transcript isoforms from a single gene. It is thought that this process can be subject to epigenetic regulation, but few specific examples of this have been reported. We previously showed that the Mcts2/H13 locus is subject to genomic imprinting and that alternative polyadenylation of H13 transcripts occurs in an allele-specific manner, regulated by epigenetic mechanisms. Here, we demonstrate that allele-specific polyadenylation occurs at another im-printed locus with similar features. Nap1l5 is a retrogene expressed from the paternally inherited allele, is situated within an intron of a ‘host ’ gene Herc3, and overlaps a CpG island that is differen-tially methylated between the parental alleles. In mouse brain, internal Herc3 polyadenylation sites upstream of Nap1l5 are used on the pater-nally derived chromosome, from which Nap1l5 is expressed, whereas a downstream site is used more frequently on the maternally derived chromo-some. Ablating DNA methylation on the maternal allele at the Nap1l5 promoter increases the use of an internal Herc3 polyadenylation site and alters exon splicing. These changes demonstrate the influ-ence of epigenetic mechanisms in regulating Herc3 alternative mRNA processing. Internal Herc3 polyadenylation correlates with expression levels of Nap1l5, suggesting a possible role for transcrip-tional interference. Similar mechanisms may regulate alternative polyadenylation elsewhere in the genome

Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci

This is an Open Access article. © 2015 The Author(s). Published by Springer Berlin Heidelberg.The susceptibility of 12 field-collected isolates and 4 laboratory strains of cat fleas, Ctenocephalides felis was determined by topical application of some of the insecticides used as on-animal therapies to control them. In the tested field-collected flea isolates the LD50 values for fipronil and imidacloprid ranged from 0.09 to 0.35 ng/flea and 0.02 to 0.19 ng/flea, respectively, and were consistent with baseline figures published previously. The extent of variation in response to four pyrethroid insecticides differed between compounds with the LD50 values for deltamethrin ranging from 2.3 to 28.2 ng/flea, etofenprox ranging from 26.7 to 86.7 ng/flea, permethrin ranging from 17.5 to 85.6 ng/flea, and d-phenothrin ranging from 14.5 to 130 ng/flea. A comparison with earlier data for permethrin and deltamethrin implied a level of pyrethroid resistance in all isolates and strains. LD50 values for tetrachlorvinphos ranged from 20.0 to 420.0 ng/flea. The rdl mutation (conferring target-site resistance to cyclodiene insecticides) was present in most field-collected and laboratory strains, but had no discernible effect on responses to fipronil, which acts on the same receptor protein as cyclodienes. The kdr and skdr mutations conferring target-site resistance to pyrethroids but segregated in opposition to one another, precluding the formation of genotypes homozygous for both mutations.Peer reviewedFinal Published versio

Visual Decision-Support for Live Digital Forensics

Performing a live digital forensics investigation on a running system is challenging due to the time pressure under which decisions have to be made. Newly proliferating and frequently applied types of malware (e.g., fileless malware) increase the need to conduct digital forensic investigations in real-time. In the course of these investigations, forensic experts are confronted with a wide range of different forensic tools. The decision, which of those are suitable for the current situation, is often based on the cyber forensics experts' experience. Currently, there is no reliable automated solution to support this decision-making. Therefore, we derive requirements for visually supporting the decision-making process for live forensic investigations and introduce a research prototype that provides visual guidance for cyber forensic experts during a live digital forensics investigation. Our prototype collects relevant core information for live digital forensics and provides visual representations for connections between occurring events, developments over time, and detailed information on specific events. To show the applicability of our approach, we analyze an exemplary use case using the prototype and demonstrate the support through our approach

ForCyRange: An Educational IoT Cyber Range for Live Digital Forensics

The Internet of Things (IoT) is finding increasing application in different areas, whether for private users or in industrial plants. The IoT increases the attack surface for Advanced Persistent Threats (APTs) due to insufficiently secured IoT devices and networks. The heterogeneous structure of the IoT poses several new challenges for the application of IoT forensics (IoTF). Due to limited resources and storage capacity on the devices, the application of traditional forensics is not possible. Therefore, the nature of these IoT devices urges forensic experts to extract and analyze possibly relevant data in a real-time manner from running devices by applying Live Digital Forensics (LDF). Although LDF investigations are not commonly applied in the IoT context yet, IoTF could benefit largely from a combined arms approach with LDF. Thus, security experts with sufficient skills and knowledge will be required to perform such procedures. Addressing the challenge to equip future forensic experts with these skills and knowledge, we propose a concept for an educational IoT Cyber Range for LDF for postgraduate cybersecurity learners. For a realistic learning experience, we outline the simulation of a simplistic, underlying IoT system. In order to create an environment that is as realistic as possible, we describe an illustrative scenario that serves as a motivational story. Following the scenario, learners carry out several tasks of an IoTF investigation for solving the scenario

Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat

<p>Abstract</p> <p>Background</p> <p>The dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin at the heart of the dystrophin glycoprotein complex in the main clinically affected tissues (skeletal muscle, heart and brain) is its distant relative, α-dystrobrevin. The α-dystrobrevin gene is subject to complex transcriptional and post-transcriptional regulation, generating a substantial range of isoforms by alternative promoter use, alternative polyadenylation and alternative splicing. The choice of isoform is understood, amongst other things, to determine the stoichiometry of syntrophins (and their ligands) in the dystrophin glycoprotein complex.</p> <p>Results</p> <p>We show here that, contrary to the literature, most α-dystrobrevin genes, including that of humans, encode three distinct syntrophin-binding sites, rather than two, resulting in a greatly enhanced isoform repertoire. We compare in detail the quantitative tissue-specific expression pattern of human and mouse α-dystrobrevin isoforms, and show that two major gene features (the novel syntrophin-binding site-encoding exon and the internal promoter and first exon of brain-specific isoforms α-dystrobrevin-4 and -5) are present in most mammals but specifically ablated in mouse and rat.</p> <p>Conclusion</p> <p>Lineage-specific mutations in the murids mean that the mouse brain has fewer than half of the α-dystrobrevin isoforms found in the human brain. Our finding that there are likely to be fundamental functional differences between the α-dystrobrevins (and therefore the dystrophin glycoprotein complexes) of mice and humans raises questions about the current use of the mouse as the principal model animal for studying Duchenne muscular dystrophy and other related disorders, especially the neurological aspects thereof.</p