Objective The aim of the present study was to explore the use of complementary consent methodologies to support a potentially vulnerable group of people, namely those aging with intellectual ...disability, to provide personal input. It was premised on the view that processes to determine capacity for consent, appropriately modified to account for individual capabilities and current circumstances, could facilitate meaningful participation in the development of personal health care plans of people previously excluded from contributing. Methods The present descriptive case study research was undertaken in New South Wales, Australia. A seven-step process for determining capacity for consent was developed, and 10 participants aged between 54 and 73 years with lifelong intellectual disability and health comorbidities were involved. A variety of assistive communication tools was used to support individuals to demonstrate their capacity for giving informed consent. Results After being provided with tailored support mechanisms, seven participants were considered to meet all seven components for determining capacity for consent. Three participants were deemed not to have capacity to give consent regardless of the type of support provided. Conclusions Three critical factors for facilitating personal involvement in decision making for individuals with an intellectual disability were identified: (1) defining consent specifically for the target outcome; (2) outlining the criteria needed for consent to be obtained; and (3) using appropriately modified alternative communication mechanisms as necessary. What is known about the topic? Self-determination is one of the fundamental principles of human rights legislation around the world and, as such, it is considered desirable to have personal input by individuals into the development of their own health care plans. However, this is not always considered feasible if the person comes from a group in the community perceived to be vulnerable to exploitation and viewed as lacking capacity to give informed consent. This results in the use of proxy respondents, who may not accurately represent the desires and life aspirations of the individual. What does this paper add? This paper examines the development and implementation of a targeted program to support individuals aging with lifelong intellectual disability to demonstrate their capacity to provide informed consent. Specifically, it outlines how alternative communications methods, tailored to personal needs and capacity, can assist an individual to both understand and then confirm their understanding of consent in order to participate in developing health care plans. What are the implications for practitioners? People with intellectual disability are now living longer and are increasingly at risk of serious health conditions. The development of long-term health management plans has traditionally not included individuals with more complex needs and moderate intellectual disability, but the present study shows that members of this cohort can successfully understand and consent to participate in health care decision making. By proactively supporting this process, community and healthcare settings may be able to directly facilitate contribution from more individuals, therefore better meeting the goal of person-centred support.
Digital mobility assessment using wearable sensor systems has the potential to capture walking performance in a patient's natural environment. It enables monitoring of health status and disease ...progression and evaluation of interventions in real-world situations. In contrast to laboratory settings, real-world walking occurs in non-conventional environments and under unconstrained and uncontrolled conditions. Despite the general understanding, there is a lack of agreed definitions about what constitutes real-world walking, impeding the comparison and interpretation of the acquired data across systems and studies. The goal of this study was to obtain expert-based consensus on specific aspects of real-world walking and to provide respective definitions in a common terminological framework. An adapted Delphi method was used to obtain agreed definitions related to real-world walking. In an online survey, 162 participants from a panel of academic, clinical and industrial experts with experience in the field of gait analysis were asked for agreement on previously specified definitions. Descriptive statistics was used to evaluate whether consent (> 75% agreement as defined a priori) was reached. Of 162 experts invited to participate, 51 completed all rounds (31.5% response rate). We obtained consensus on all definitions ("Walking" > 90%, "Purposeful" > 75%, "Real-world" > 90%, "Walking bout" > 80%, "Walking speed" > 75%, "Turning" > 90% agreement) after two rounds. The identification of a consented set of real-world walking definitions has important implications for the development of assessment and analysis protocols, as well as for the reporting and comparison of digital mobility outcomes across studies and systems. The definitions will serve as a common framework for implementing digital and mobile technologies for gait assessment and are an important link for the transition from supervised to unsupervised gait assessment.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diskriminierungen und Benachteiligungen gehören für viele Menschen zu allgegenwärtigen Erfahrungen des Alltags. Während Diskriminierungen zum Beispiel aufgrund von Behinderung oder Geschlecht mit ...gesetzlichen Vorkehrungen begegnet wird, gelten Benachteiligungen aufgrund der sozialen Lage noch immer als sozial legitimiert, wenn sie auf individuellen Leistungsdifferenzen beruhen.Arne Müller hinterfragt und kritisiert diese Unterscheidung mit dem theoretischen Rüstzeug Pierre Bourdieus. Seine empirische Untersuchung der Wechselwirkungen von Behinderung, Geschlecht und sozialer Lage liefert viele neue und instruktive Einsichten.
The majority of efforts in the field of sim-to-real Deep Reinforcement Learning focus on robot manipulators, which is justified by their importance for modern production plants. However, there are ...only a few studies for a more extensive use in manufacturing processes. In this paper, we contribute to this by automating a complex manufacturing-like process using simulation-based Deep Reinforcement Learning. The setup and workflow presented here are designed to mimic the characteristics of real manufacturing processes and proves that Deep Reinforcement Learning can be applied to physical systems built from industrial drive and control components by transferring policies learned in simulation to the real machine. Aided by domain randomization, training in a virtual environment is crucial due to the benefit of accelerated training speed and the desire for safe Reinforcement Learning. Our key contribution is to demonstrate the applicability of simulation-based Deep Reinforcement Learning in industrial automation technology. We introduce an industrial drive and control system, based on the classic pub game Foosball, from both an engineering and a simulation perspective, describing the strategies applied to increase transfer robustness. Our approach allowed us to train a self-learning agent to independently learn successful control policies for demanding Foosball tasks based on sparse reward signals. The promising results prove that state-of-the-art Deep Reinforcement Learning algorithms are able to produce models trained in simulation, which can successfully control industrial use cases without using the actual system for training beforehand.
A technique for determining the material-specific morphology of a polymer–fullerene blend is presented. This technique is applied to solution processed bulk-heterojunction organic solar cells with ...different weight ratios of polymer–fullerene blend using the PTB7:PCBM material system. Optical and electrical characterizations show that the light absorption increases for larger polymer (PTB7) content, while the fill factor of the fabricated solar cells is improved for larger fullerene (PCBM) content. The material-specific morphologies of polymer–fullerene bulk-heterojunctions are measured by employing AFM phase imaging. The measured AFM phase images reveal that fullerene material forms flake-like clusters which are embedded in the polymer network. The size of the flakes is increasing with larger content of fullerene material. By correlating the optical and electrical properties with the measured bulk-heterojunction morphologies, the relation between bulk-heterojunction structure and solar cell performances is discussed.
Flux variability analysis (FVA) is an important tool to further analyse the results obtained by flux balance analysis (FBA) on genome-scale metabolic networks. For many constraint-based models, FVA ...identifies unboundedness of the optimal flux space. This reveals that optimal flux solutions with net flux through internal biochemical loops are feasible, which violates the second law of thermodynamics. Such unbounded fluxes may be eliminated by extending FVA with thermodynamic constraints.
We present a new algorithm for efficient flux variability (and flux balance) analysis with thermodynamic constraints, suitable for analysing genome-scale metabolic networks. We first show that FBA with thermodynamic constraints is NP-hard. Then we derive a theoretical tractability result, which can be applied to metabolic networks in practice. We use this result to develop a new constraint programming algorithm Fast-tFVA for fast FVA with thermodynamic constraints (tFVA). Computational comparisons with previous methods demonstrate the efficiency of the new method. For tFVA, a speed-up of factor 30-300 is achieved. In an analysis of genome-scale metabolic networks in the BioModels database, we found that in 485 of 716 networks, additional irreversible or fixed reactions could be detected.
Fast-tFVA is written in C++ and published under GPL. It uses the open source software SCIP and libSBML. There also exists a Matlab interface for easy integration into Matlab. Fast-tFVA is available from page.mi.fu-berlin.de/arnem/fast-tfva.html.
Supplementary data are available at Bioinformatics online.
Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system ...and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.
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•Global chromatin proteomics reveal TP53 stabilization in SARS-CoV-2 infection•Host cell spike expression drives TP53 stabilization and chromatin accessibility changes•Fusogenicity of variant spikes affects TP53, chromatin accessibility, and senescence
Lee et al. find that spike-mediated cell-cell fusion triggers TP53 stabilization, chromatin accessibility changes, and activation of senescence. The extent of these effects differs based on the fusogenicity of various SARS-CoV-2 variant spike sequences.
We retrospectively analyzed all endovascular procedures of infrapopliteal arterial lesions (n = 383) performed in 270 patients at our institution between December 2008 and January 2018. The overall ...technical success rate was 97% and yielded 98% for stenoses (n = 214) and 95% for occlusions (n = 169). Trans-Atlantic Inter-Society Consensus (TASC II) classification had no impact on success rates (TASC A + B vs C + D; 96.5% vs 96.9%, p = 0.837). Freedom from clinically driven target lesion revascularization (TLR) after 6 and 12 months was 88.3% and 77.2%. TLR was comparable for TASC A to C lesions and no difference was observed comparing groups of moderately complex TASC A/B lesions and more complex TASC C/D lesions (TASC A + B vs C + D; 78.5% vs 74.2%, p = 0.457). Freedom from TLR was significantly lower in very complex TASC D lesions (TASC A + B + C vs D; 79.7% vs 42.5%, p < 0.001). Multivariate analysis identified TASC D lesions (hazard ratio D/A: 1.5; overall p = 0.002), Fontaine class III and IV (hazard ratio III or IV/IIa or IIb: 2.4; p = 0.041), and occlusive lesions (hazard ratio occlusion/stenosis: 2.4; p = 0.026) as predictors for TLR. In conclusion, endovascular therapy for infrapopliteal artery disease was safe and accompanied with a promising long-term outcome.
We retrospectively analyzed patient records of all patients with a history of internal mammarian artery (IMA) coronary bypass undergoing coronary angiography at two cardiovascular centers between ...January 1st 1999 and December 31st 2019. A total of 11,929 coronary angiographies with or without percutaneous coronary intervention were carried out in 3921 patients. Our analysis revealed 82 (2%) patients with documented subclavian artery stenosis. Of these, 8 (10%) patients were classified as having mild, 18 (22%) moderate, and 56 (68%) severe subclavian artery stenosis. In 7 (9%) patients with subclavian artery stenosis, angiography revealed occlusion of the IMA graft. 26 (32%) patients with severe subclavian artery stenosis underwent endovascular or surgical revasculararization of the subclavian artery. In this retrospective multicenter study, subclavian artery stenosis was a relevant finding in patients with an internal mammarian artery coronary bypass graft undergoing coronary angiography. The development of dedicated algorithms for screening and ischemia evaluation in affected individuals may improve treatment of this potentially underdiagnosed and undertreated condition.
Evidence suggests that epigenetic perturbations are involved in the adverse effects associated with some drugs and toxicants, including certain classes of non-genotoxic carcinogens. Such epigenetic ...changes (altered DNA methylation and covalent histone modifications) may take place at the earliest stages of carcinogenesis and their identification holds great promise for biomedical research. Here, we evaluate the sensitivity and specificity of genome-wide epigenomic and transcriptomic profiling in phenobarbital (PB)-treated B6C3F1 mice, a well-characterized rodent model of non-genotoxic liver carcinogenesis. Methylated DNA Immunoprecipitation (MeDIP)-coupled microarray profiling of 17,967 promoter regions and 4,566 intergenic CpG islands was combined with genome-wide mRNA expression profiling to identify liver tissue-specific PB-mediated DNA methylation and transcriptional alterations. Only a limited number of significant anti-correlations were observed between PB-induced transcriptional and promoter-based DNA methylation perturbations. However, the constitutive androstane receptor (CAR) target gene Cyp2b10 was found to be concomitantly hypomethylated and transcriptionally activated in a liver tissue-specific manner following PB treatment. Furthermore, analysis of active and repressive histone modifications using chromatin immunoprecipitation revealed a strong PB-mediated epigenetic switch at the Cyp2b10 promoter. Our data reveal that PB-induced transcriptional perturbations are not generally associated with broad changes in the DNA methylation status at proximal promoters and suggest that the drug-inducible CAR pathway regulates an epigenetic switch from repressive to active chromatin at the target gene Cyp2b10. This study demonstrates the utility of integrated epigenomic and transcriptomic profiling for elucidating early mechanisms and biomarkers of non-genotoxic carcinogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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