Good Care in Ongoing Dialogue. Improving the Quality of Care Through Moral Deliberation and Responsive Evaluation

Recently, moral deliberation within care institutions is gaining more attention in medical ethics. Ongoing dialogues about ethical issues are considered as a vehicle for quality improvement of health care practices. The rise of ethical conversation methods can be understood against the broader development within medical ethics in which interaction and dialogue are seen as alternatives for both theoretical or individual reflection on ethical questions. In other disciplines, intersubjectivity is also seen as a way to handle practical problems, and methodologies have emerged to deal with dynamic processes of practice improvement. An example is responsive evaluation. In this article we investigate the relationship between moral deliberation and responsive evaluation, describe their common basis in dialogical ethics and pragmatic hermeneutics, and explore the relevance of both for improving the quality of care. The synergy between the approaches is illustrated by a case example in which both play a distinct and complementary role. It concerns the implementation of quality criteria for coercion in Dutch psychiatry

Gene Conversion Transfers the GAF-A Domain of Phosphodiesterase TbrPDEB1 to One Allele of TbrPDEB2 of Trypanosoma brucei

Cyclic nucleotide specific phosphodiesterases are important regulators of cyclic nucleotide signalling in eukaryotes. In many organisms, including humans and trypanosomes, some of these enzymes contain specific domains (GAF domains) that bind cyclic nucleotides, and that are involved in the regulation of the catalytic domain. In the parasitic protozoon that causes human sleeping sickness, Trypanosoma brucei, two closely related phosphodiesterases each contain two such GAF domains, GAF-A and GAF-B. Their genes are tandemly located on chromosome 9, spaced by only a few thousand nucleotides. We here show that a gene conversion event has exchanged the region that codes for the GAF-A domain of the downstream gene by the closely similar corresponding sequence of the upstream gene. This domain exchange has no effect on intracellular localization of the two enzymes. The gene conversion event has occurred in one particular strain of trypanosomes (Lister427) and is found in all its derivatives, but not in any other strain or isolate. The presence or absence of this gene conversion represents a useful analytical marker for the stringent discrimination of Lister427 derivatives from other trypanosome strains

An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine

An investigation into the depth of penetration of low level laser therapy through the equine tendon in vivo

Low level laser therapy (LLLT) is frequently used in the treatment of wounds, soft tissue injury and in pain management. The exact penetration depth of LLLT in human tissue remains unspecified. Similar uncertainty regarding penetration depth arises in treating animals. This study was designed to test the hypothesis that transmission of LLLT in horses is increased by clipping the hair and/or by cleaning the area to be treated with alcohol, but is unaffected by coat colour. A LLLT probe (810 nm, 500 mW) was applied to the medial aspect of the superficial flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied to the lateral aspect, directly opposite the laser probe to measure the amount of light transmitted. Light transmission was not affected by individual horse, coat colour or leg. However, it was associated with leg condition (F = 4.42, p = 0.0032). Tendons clipped dry and clipped and cleaned with alcohol, were both associated with greater transmission of light than the unprepared state. Use of alcohol without clipping was not associated with an increase in light transmission. These results suggest that, when applying laser to a subcutaneous structure in the horse, the area should be clipped and cleaned beforehand

Characterization and mitigation of gene expression burden in mammalian cells

Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of otherwise independent exogenous and endogenous genes, creating a divergence between intended and actual function. Guided by a resource-aware mathematical model, we identify and engineer natural and synthetic miRNA-based incoherent feedforward loop (iFFL) circuits that mitigate gene expression burden. The implementation of these circuits features the use of endogenous miRNAs as elementary components of the engineered iFFL device, a versatile hybrid design that allows burden mitigation to be achieved across different cell-lines with minimal resource requirements. This study establishes the foundations for context-aware prediction and improvement of in vivo synthetic circuit performance, paving the way towards more rational synthetic construct design in mammalian cells

Prognostic factors for disability claim duration due to musculoskeletal symptoms among self-employed persons

<p>Abstract</p> <p>Background</p> <p>Employees and self-employed persons have, among others, different personal characteristics and different working conditions, which may influence the prognosis of sick leave and the duration of a disability claim. The purpose of the current study is to identify prognostic factors for the duration of a disability claim due to non-specific musculoskeletal disorders (MSD) among self-employed persons in the Netherlands.</p> <p>Methods</p> <p>The study population consisted of 276 self-employed persons, who all had a disability claim episode due to MSD with at least 75% work disability. The study was a cohort study with a follow-up period of 12 months. At baseline, participants filled in a questionnaire with possible individual, work-related and disease-related prognostic factors.</p> <p>Results</p> <p>The following prognostic factors significantly increased claim duration: age > 40 years (Hazard Ratio 0.54), no similar symptoms in the past (HR 0.46), having long-lasting symptoms of more than six months (HR 0.60), self-predicted return to work within more than one month or never (HR 0.24) and job dissatisfaction (HR 0.54).</p> <p>Conclusions</p> <p>The prognostic factors we found indicate that for self-employed persons, the duration of a disability claim not only depends on the (history of) impairment of the insured, but also on age, self-predicted return to work and job satisfaction.</p

Appropriate model use for predicting elevations and inundation extent for extreme flood events

Flood risk assessment is generally studied using flood simulation models; however, flood risk managers often simplify the computational process; this is called a “simplification strategy”. This study investigates the appropriateness of the “simplification strategy” when used as a flood risk assessment tool for areas prone to flash flooding. The 2004 Boscastle, UK, flash flood was selected as a case study. Three different model structures were considered in this study, including: (1) a shock-capturing model, (2) a regular ADI-type flood model and (3) a diffusion wave model, i.e. a zero-inertia approach. The key findings from this paper strongly suggest that applying the “simplification strategy” is only appropriate for flood simulations with a mild slope and over relatively smooth terrains, whereas in areas susceptible to flash flooding (i.e. steep catchments), following this strategy can lead to significantly erroneous predictions of the main parameters—particularly the peak water levels and the inundation extent. For flood risk assessment of urban areas, where the emergence of flash flooding is possible, it is shown to be necessary to incorporate shock-capturing algorithms in the solution procedure, since these algorithms prevent the formation of spurious oscillations and provide a more realistic simulation of the flood levels

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell

Modeling of Intermediate Structures and Chain Conformation in Silica-Latex Nanocomposites Observed by SANS During Annealing

The evolution of the polymer structure during nanocomposite formation and annealing of silica-latex nanocomposites is studied using contrast-variation small angle neutron scattering. The experimental system is made of silica nanoparticles (Rsi \approx 8 nm) and a mixture of purpose-synthesized hydrogenated and deuterated nanolatex (Rlatex \approx 12.5 nm). The progressive disappearance of the latex beads by chain interdiffusion and release in the nanocomposites is analyzed quantitatively with a model for the scattered intensity of hairy latex beads and an RPA description of the free chains. In silica-free matrices and nanocomposites of low silica content (7%v), the annealing procedure over weeks at up to Tg + 85 K results in a molecular dispersion of chains, the radius of gyration of which is reported. At higher silica content (20%v), chain interdiffusion seems to be slowed down on time-scales of weeks, reaching a molecular dispersion only at the strongest annealing. Chain radii of gyration are found to be unaffected by the presence of the silica filler