Adapting to domiciliary non-invasive ventilation in chronic obstructive pulmonary disease:a qualitative interview study

Background: Domiciliary non-invasive ventilation may be used in palliative care of patients with chronic obstructive pulmonary disease, although there is uncertainty regarding effect on quality of life. Aim: Explore experiences of domiciliary non-invasive ventilation in chronic obstructive pulmonary disease, to understand decision-making processes and improve future palliative care. Design: Qualitative interview study, based on constructivist grounded theory, and using the framework method for data management and analysis. Participants: 20 chronic obstructive pulmonary disease patients, 4 carers and 15 healthcare professionals. Results: Most patients had very severe chronic obstructive pulmonary disease. Data were categorised into four domains – clinical, technical, socio-economic and experiential. Healthcare professionals felt uncertain regarding clinical evidence, emphasising social support and tolerance as deciding factors in non-invasive ventilation use. Conversely, patients reported symptomatic benefit, which generally outweighed negative experiences and led to continued use. Healthcare professionals felt that patients chose to be on non-invasive ventilation; however, most patients felt that they had no choice as healthcare professionals recommended non-invasive ventilation or their poor health mandated it. Conclusions: Our study identifies ‘adapting to non-invasive ventilation’ as the central process enabling long-term use in palliative care, although the way in which this is approached by healthcare professionals and patients does not always converge. We present ideas emerging from the data on potential interventions to improve patient experience and adaptation. </jats:sec

Crystal Structure and Twisted Aggregates of Oxcarbazepine Form III

Polymorphism and crystal habit play vital roles in dictating the properties of crystalline materials. Here, the structure and properties of oxcarbazepine (OXCBZ) form III are reported along with the occurrence of twisted crystalline aggregates of this metastable polymorph. OXCBZ III can be produced by crystallization from the vapor phase and by recrystallization from solution. The crystallization process used to obtain OXCBZ III is found to affect the pitch, with the most prominent effect observed from the sublimation-grown OXCBZ III material where the pitch increases as the length of aggregates increases. Sublimation-grown OXCBZ III follows an unconventional mechanism of formation with condensed droplet formation and coalescence preceding nucleation and growth of aggregates. A crystal structure determination of OXCBZ III from powder X-ray diffraction methods, assisted by crystal structure prediction (CSP), reveals that OXCBZ III, similar to carbamazepine form II, contains void channels in its structure with the channels, aligned along the c crystallographic axis, oriented parallel to the twist axis of the aggregates. The likely role of structural misalignment at the lattice or nanoscale is explored by considering the role of molecular and closely related structural impurities informed by crystal structure prediction

Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

The P2X3 receptor antagonist filapixant in patients with refractory chronic cough: a randomized controlled trial

BACKGROUND: P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled study, we investigated the efficacy, safety, and tolerability of the novel selective P2X3 receptor antagonist filapixant (BAY1902607) in patients with refractory chronic cough. METHODS: Following a crossover design, 23 patients with refractory chronic cough (age: 60.4 ± 9.1 years) received ascending doses of filapixant in one period (20, 80, 150, and 250 mg, twice daily, 4-days-on/3-days-off) and placebo in the other. The primary efficacy endpoint was the 24-h cough frequency on Day 4 of each dosing step. Further, subjective cough severity and health-related quality of life were assessed. RESULTS: Filapixant at doses ≥ 80 mg significantly reduced cough frequency and severity and improved cough health-related quality of life. Reductions in 24-h cough frequency over placebo ranged from 17% (80 mg dose) to 37% (250 mg dose), reductions over baseline from 23% (80 mg) to 41% (250 mg) (placebo: 6%). Reductions in cough severity ratings on a 100-mm visual analog scale ranged from 8 mm (80 mg) to 21 mm (250 mg). No serious or severe adverse events or adverse events leading to discontinuation of treatment were reported. Taste-related adverse events occurred in 4%, 13%, 43%, and 57% of patients treated with filapixant 20, 80, 150, and 250 mg, respectively, and in 12% treated with placebo. CONCLUSIONS: Filapixant proved to be efficacious, safe, and-apart from the occurrence of taste disturbances, especially at higher dosages-well tolerated during the short therapeutic intervention. Clinical trial registration EudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168

Twelve tips for organising speed mentoring events for healthcare professionals at small or large-scale venues

Mentors play a critical role in the development of professionals, influencing their job satisfaction, career aspirations and evolving professional identity. A variety of mentoring models exist, each with distinct benefits and challenges. Speed mentoring, based on the concept of speed dating, provides mentees with opportunities to meet multiple mentors over a short time and pose focussed career development questions. At large-scale events such as the annual AMEE (Association for Medical Education in Europe) meeting, speed mentoring sessions can successfully connect aspiring, novice and mid-career educators with international educational leaders to facilitate transfer of valuable insights for professional growth. For some mentors and mentees, this might spur ongoing communications or even longitudinal relationships. In this paper, we aim to provide strategies for planning and implementing speed mentoring events, combining insights gained from the literature and our experience of organising speed mentoring at the 2019 AMEE meeting in Vienna. These tips will be useful to a variety of professionals planning to organise speed mentoring initiatives

Deep learning‐based quantification of arbuscular mycorrhizal fungi in plant roots

Summary: Soil fungi establish mutualistic interactions with the roots of most vascular land plants. Arbuscular mycorrhizal (AM) fungi are among the most extensively characterised mycobionts to date. Current approaches to quantifying the extent of root colonisation and the abundance of hyphal structures in mutant roots rely on staining and human scoring involving simple yet repetitive tasks which are prone to variation between experimenters. We developed Automatic Mycorrhiza Finder (AMFinder) which allows for automatic computer vision‐based identification and quantification of AM fungal colonisation and intraradical hyphal structures on ink‐stained root images using convolutional neural networks. AMFinder delivered high‐confidence predictions on image datasets of roots of multiple plant hosts (Nicotiana benthamiana, Medicago truncatula, Lotus japonicus, Oryza sativa) and captured the altered colonisation in ram1‐1, str, and smax1 mutants. A streamlined protocol for sample preparation and imaging allowed us to quantify mycobionts from the genera Rhizophagus, Claroideoglomus, Rhizoglomus and Funneliformis via flatbed scanning or digital microscopy, including dynamic increases in colonisation in whole root systems over time. AMFinder adapts to a wide array of experimental conditions. It enables accurate, reproducible analyses of plant root systems and will support better documentation of AM fungal colonisation analyses. AMFinder can be accessed at https://github.com/SchornacklabSLCU/amfinder

From clinical educators to educational scholars and leaders: strategies for developing and advancing a career in health professions education

This toolbox article provides ideas and recommendations for academic and clinical educators seeking roles as educational scholars and leaders

Crystal structure and twisted aggregates of oxcarbazepine form III

Polymorphism and crystal habit play vital roles in dictating the properties of crystalline materials. Here, the structure and properties of oxcarbazepine (OXCBZ) form III are reported along with the occurrence of twisted crystalline aggregates of this metastable polymorph. OXCBZ III can be produced by crystallization from the vapor phase and by recrystallization from solution. The crystallization process used to obtain OXCBZ III is found to affect the pitch, with the most prominent effect observed from the sublimation-grown OXCBZ III material where the pitch increases as the length of aggregates increases. Sublimation-grown OXCBZ III follows an unconventional mechanism of formation with condensed droplet formation and coalescence preceding nucleation and growth of aggregates. A crystal structure determination of OXCBZ III from powder X-ray diffraction methods, assisted by crystal structure prediction (CSP), reveals that OXCBZ III, similar to carbamazepine form II, contains void channels in its structure with the channels, aligned along the c crystallographic axis, oriented parallel to the twist axis of the aggregates. The likely role of structural misalignment at the lattice or nanoscale is explored by considering the role of molecular and closely related structural impurities informed by crystal structure prediction

Phenotypic screen for oxygen consumption rate identifies an anti-cancer naphthoquinone that induces mitochondrial oxidative stress.

A hallmark of cancer cells is their ability to reprogram nutrient metabolism. Thus, disruption to this phenotype is a potential avenue for anti-cancer therapy. Herein we used a phenotypic chemical library screening approach to identify molecules that disrupted nutrient metabolism (by increasing cellular oxygen consumption rate) and were toxic to cancer cells. From this screen we discovered a 1,4-Naphthoquinone (referred to as BH10) that is toxic to a broad range of cancer cell types. BH10 has improved cancer-selective toxicity compared to doxorubicin, 17-AAG, vitamin K3, and other known anti-cancer quinones. BH10 increases glucose oxidation via both mitochondrial and pentose phosphate pathways, decreases glycolysis, lowers GSH:GSSG and NAPDH/NAPD+ ratios exclusively in cancer cells, and induces necrosis. BH10 targets mitochondrial redox defence as evidenced by increased mitochondrial peroxiredoxin 3 oxidation and decreased mitochondrial aconitase activity, without changes in markers of cytosolic or nuclear damage. Over-expression of mitochondria-targeted catalase protects cells from BH10-mediated toxicity, while the thioredoxin reductase inhibitor auranofin synergistically enhances BH10-induced peroxiredoxin 3 oxidation and cytotoxicity. Overall, BH10 represents a 1,4-Naphthoquinone with an improved cancer-selective cytotoxicity profile via its mitochondrial specificity

Domestic cats (Felis silvestris catus) do not show signs of secure attachment to their owners

The Ainsworth Strange Situation Test (SST) has been widely used to demonstrate that the bond between both children and dogs to their primary carer typically meets the requirements of a secure attachment (i.e. the carer being perceived as a focus of safety and security in otherwise threatening environments), and has been adapted for cats with a similar claim made. However methodological problems in this latter research make the claim that the cat-owner bond is typically a secure attachment, operationally definable by its behaviour in the SST, questionable. We therefore developed an adapted version of the SST with the necessary methodological controls which include a full counterbalance of the procedure. A cross-over design experiment with 20 cat-owner pairs (10 each undertaking one of the two versions of the SST first) and continuous focal sampling was used to record the duration of a range of behavioural states expressed by the cats that might be useful for assessing secure attachment. Since data were not normally distributed, non-parametric analyses were used on those behaviours shown to be reliable across the two versions of the test (which excluded much cat behaviour). Although cats vocalised more when the owner rather the stranger left the cat with the other individual, there was no other evidence consistent with the interpretation of the bond between a cat and its owner meeting the requirements of a secure attachment. These results are consistent with the view that adult cats are typically quite autonomous, even in their social relationships, and not necessarily dependent on others to provide a sense of security and safety. It is concluded that alternative methods need to be developed to characterise the normal psychological features of the cat-owner bond