Adaptive neural network control of fes-induced cyclical lower leg movements

As a first step to the control of paraplegic gait by functional electrical stimulation (FES), the control of the swinging lower leg is being studied. This paper deals with a neural control system, that has been developed for this case. The control system has been tested for a model of the swinging lower leg using computer simulations. The neural controller was trained by supervised learning (SL) and by backpropagation through time (BTT). The performance of the controller with random initial weights was poor after training with BTT and fair after SL. BTT training of the neural controller with weights, which had been initialized by SL, resulted in good control. Training with BTT thus improved the performance of the controller that initially had been trained by SL. An adaptive neural control system based on BTT has been proposed and partially tested. The controller adapted relatively fast to the change of an important model parameter

Assessing excellence in translational cancer research: a consensus based framework

Background: It takes several years on average to translate basic research findings into clinical research and eventually deliver patient benefits. An expert-based excellence assessment can help improve this process by: identifying high performing Comprehensive Cancer Centres; best practices in translational cancer research; improving the quality and efficiency of the translational cancer research process. This can help build networks of excellent Centres by aiding focused partnerships. In this paper we report on a consensus building exercise that was undertaken to construct an excellence assessment framework for translational cancer research in Europe. Methods: We used mixed methods to reach consensus: a systematic review of existing translational research models critically appraised for suitability in performance assessment of Cancer Centres; a survey among European stakeholders (researchers, clinicians, patient representatives and managers) to score a list of potential excellence criteria, a focus group with selected representatives of survey participants to review and rescore the excellence criteria; an expert group meeting to refine the list; an open validation round with stakeholders and a critical review of the emerging framework by an independent body: a committee formed by the European Academy of Cancer Sciences. Results: The resulting excellence assessment framework has 18 criteria categorized in 6 themes. Each criterion has a number of questions/sub-criteria. Stakeholders favoured using qualitative excellence criteria to evaluate the translational research “process” rather than quantitative criteria or judging only the outputs. Examples of criteria include checking if the Centre has mechanisms that can be rated as excellent for: involvement of basic researchers and clinicians in translational research (quality of supervision and incentives provided to clinicians to do a PhD in translational research) and well designed clinical trials based on ground-breaking concepts (innovative patient stratification, substantial fraction of phase I/II trials, investigator-initiated trials). Critically, the framework supports reduced bureaucracy by building on existing European evaluation systems. Conclusions: The excellence framework is the product of an intense stakeholder consensus building exercise. It will be piloted during an expert peer review/site visit of at least three European Comprehensive Cancer Centres. The findings regarding content, governance and implementation can have relevance for other clinical and research fields

Overcoming the Digital Divide for Older Patients With Respiratory Disease: Focus Group Study

Background: The need for and adoption of eHealth programs are growing worldwide. However, access can be limited among patients with low socioeconomic backgrounds, often resulting in a so-called “digital divide” due to a mismatch between eHealth and target populations that can gain benefit. This digital divide can result in unsuccessful eHealth implementations, which is of critical importance to health care.Objective: This study evaluated the opinions of elderly patients with asthma and chronic obstructive pulmonary disease (COPD) about an existing pharmacy-based personalized patient web portal that provides medication overview and information on associated diagnoses. The aim was to obtain insights on the common barriers of elderly people when using health-related websites, which can help to improve accessibility.Methods: This was a cross-sectional qualitative study of a patient panel of the Groningen Research Institute for Asthma and COPD in primary care. Participants were required to be older than 55 years, be Dutch speaking, have no prior experience with the study website, and be diagnosed with a chronic respiratory illness. Two focus groups were created, and they completed a 45-minute session for testing the website and a 120-minute session for semistructured interviews. The focus group sessions were recorded, transcribed verbatim, and analyzed by content analysis.Results: We enrolled 11 patients (9 women) with a mean age of 66 (SD 9) years. Of these, 5 had asthma, 3 had COPD, 2 had asthma-COPD overlap syndrome, and 1 had bronchiectasis. Participants were generally positive about the website, especially the areas providing disease-related information and the medication overview. They appreciated that the website would enable them to share this information with other health care providers. However, some difficulties were reported with navigation, such as opening a new tab, and others reported that the layout of the website was difficult either because of visual impairments or problems with navigation. It was also felt that monitoring would only be relevant if it is also checked by health care professionals as part of a treatment plan. Participants mentioned few privacy or safety concerns.Conclusions: It is feasible to develop websites for elderly patients; however, developers must take the specific needs and limitations of elderly people into account (eg, navigation problems, poor vision, or poor hand-eye coordination). The provision of information appears to be the most important aspect of the website, and as such, we should endeavor to ensure that the layout and navigation remain basic and accessible. Patients are only motivated to use self-management applications if they are an integrated part of their treatment. The usability of the website can be improved by including older people during development and by implementing design features that can improve accessibility in this group

SERIES:eHealth in primary care. Part 4: Addressing the challenges of implementation

Background The implementation of eHealth applications in primary care remains challenging. Enhancing knowledge and awareness of implementation determinants is critical to build evidence-based implementation strategies and optimise uptake and sustainability. Objectives We consider how evidence-based implementation strategies can be built to support eHealth implementation. Discussion What implementation strategies to consider depends on (potential) barriers and facilitators to eHealth implementation in a given situation. Therefore, we first discuss key barriers and facilitators following the five domains of the Consolidated Framework for Implementation Research (CFIR). Cost is identified as a critical barrier to eHealth implementation. Privacy, security problems, and a lack of recognised standards for eHealth applications also hinder implementation. Engagement of key stakeholders in the implementation process, planning the implementation of the intervention, and the availability of training and support are important facilitators. To support care professionals and researchers, we provide a stepwise approach to develop and apply evidence-based implementation strategies for eHealth in primary care. It includes the following steps: (1) specify the eHealth application, (2) define problem, (3) specify desired implementation behaviour, and (4) choose and (5) evaluate the implementation strategy. To improve the fit of the implementation strategy with the setting, the stepwise approach considers the phase of the implementation process and the specific context. Conclusion Applying an approach, as provided here, may help to improve the implementation of eHealth applications in primary care.Prevention, Population and Disease management (PrePoD)Public Health and primary car

SERIES: eHealth in primary care. Part 1: Concepts, conditions and challenges.

Primary care is challenged to provide high quality, accessible and affordable care for an increasingly ageing, complex, and multimorbid population. To counter these challenges, primary care professionals need to take up new and innovative practices, including eHealth. eHealth applications hold the promise to overcome some difficulties encountered in the care of people with complex medical and social needs in primary care. However, many unanswered questions regarding (cost) effectiveness, integration with healthcare, and acceptability to patients, caregivers, and professionals remain to be elucidated. What conditions need to be met? What challenges need to be overcome? What downsides must be dealt with? This first paper in a series on eHealth in primary care introduces basic concepts and examines opportunities for the uptake of eHealth in primary care. We illustrate that although the potential of eHealth in primary care is high, several conditions need to be met to ensure that safe and high-quality eHealth is developed for and implemented in primary care. eHealth research needs to be optimized; ensuring evidence-based eHealth is available. Blended care, i.e. combining face-to-face care with remote options, personalized to the individual patient should be considered. Stakeholders need to be involved in the development and implementation of eHealth via co-creation processes, and design should be mindful of vulnerable groups and eHealth illiteracy. Furthermore, a global perspective on eHealth should be adopted, and eHealth ethics, patients' safety and privacy considered.Published versio

SERIES:eHealth in primary care. Part 2: Exploring the ethical implications of its application in primary care practice

Background: eHealth promises to increase self-management and personalised medicine and improve cost-effectiveness in primary care. Paired with these promises are ethical implications, as eHealth will affect patients' and primary care professionals' (PCPs) experiences, values, norms, and relationships.Objectives: We argue what ethical implications related to the impact of eHealth on four vital aspects of primary care could (and should) be anticipated.Discussion: (1) EHealth influences dealing with predictive and diagnostic uncertainty. Machine-learning based clinical decision support systems offer (seemingly) objective, quantified, and personalised outcomes. However, they also introduce new loci of uncertainty and subjectivity. The decision-making process becomes opaque, and algorithms can be invalid, biased, or even discriminatory. This has implications for professional responsibilities and judgments, justice, autonomy, and trust. (2) EHealth affects the roles and responsibilities of patients because it can stimulate self-management and autonomy. However, autonomy can also be compromised, e.g. in cases of persuasive technologies and eHealth can increase existing health disparities. (3) The delegation of tasks to a network of technologies and stakeholders requires attention for responsibility gaps and new responsibilities. (4) The triangulate relationship: patient-eHealth-PCP requires a reconsideration of the role of human interaction and 'humanness' in primary care as well as of shaping Shared Decision Making.Conclusion: Our analysis is an essential first step towards setting up a dedicated ethics research agenda that should be examined in parallel to the development and implementation of eHealth. The ultimate goal is to inspire the development of practice-specific ethical recommendations

Excellent translational research in oncology : A journey towards novel and more effective anti-cancer therapies

Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will aspire to this status. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.Peer reviewe

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets