The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark

Background: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. Objectives: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. Methods: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997�2017) and Danish nationwide registries (1997�2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. Results: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0�88 [95% confidence interval (CI) 0�84�0�92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1�17, 95% CI 1�06�1�30), with the peak occurring during the first year of follow-up (HR 1�31, 95% CI 1�07�1�60). Conclusions: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic?. Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add?. We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607�608. � 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists</p

Psoriasis and dementia: A population-based matched cohort study of adults in England

Objective: Evidence for an association between psoriasis and dementia is limited and conflicting. We aimed to investigate the association using large and representative population-based data and describe risk by dementia subtype and over time. Methods: We compared dementia risk between people with and without psoriasis using an age-, sex- and primary care practice-matched cohort of adults aged ?40 years from the Clinical Practice Research Datalink Aurum in England (1997�2021) linked to hospital admissions data, analysed with stratified Cox regression. Results: Among 360,014 individuals with psoriasis and 1,799,617 without, psoriasis was associated with a small increased risk of all-cause dementia (adjusted hazard ratio [aHR] 1.06, 95% CI 1.04�1.08; absolute rate difference 24 per 100,000 person-years). Strength of association increased with time since psoriasis diagnosis (e.g. aHR 0.99, 0.96�1.03 within 0 to 5 years; 1.20, 1.05�1.37 within 20 to 25 years). The association was stronger for vascular dementia (aHR 1.10, 1.06�1.14) than Alzheimer's dementia (aHR 1.03, 1.00�1.06). Hazard ratios were larger for severe psoriasis (all-cause aHR 1.32, 1.25�1.39; vascular aHR 1.58, 1.44�1.74; Alzheimer's aHR 1.11, 1.02�1.21). Interpretation: Long-term risk of all-cause dementia and vascular dementia, but not Alzheimer's dementia, was slightly higher in people with psoriasis, but absolute risk differences were small. Risks were more substantially raised with time since psoriasis diagnosis and in severe psoriasis compared to mild to moderate psoriasis, suggesting a potential dose�response relationship.</p

Beyond the Shrine: The Material Landscape of the Camino to Santiago

The five books of the Codex Calixtinus present many instances of natural objects and artefacts encountered by pilgrims and travelers in the environment along the Camino to Santiago. The Codex offers insight into their genesis, functions, and agency, showing how their material qualities engaged with the sensorial sphere and the imagination of beholders. This article is concerned with the issues these objects raise in relation to memory, materiality, and the senses. Scattered along the road to Santiago, these objects formed a material landscape of the Camino, creating a route of sensorial memory.</p

Remembering the early childhood home exploring a leisure lifeworld of crannies mirrors drawer knobs and corners

Taking as its starting point Gaston Bachelard’s Poetics of Space which is about architecture and environment, this paper sets out to explore the deep recesses of the home. As Bachelard writes, out of the home spin worlds within worlds where it is possible to get caught up in the remarkable dialectics of “deep” that deepens and “large” that extends beyond all limits. Focusing specifically on the home of our early childhood in a way that will hopefully resonate with most readers, the main argument is that it shelters a leisure lifeworld comprising impressions of protected intimacy and immensities that flow from objects. Having employed a methodology that is underpinned by auto-hermeneutics and ethnography, the paper should be viewed first and foremost as an attempt to recapture something that vibrates at the edges of imagination in our early years. The paper should be viewed secondly as a reminder that the value of “otherness” in our leisure lives begins in the early childhood home because this is where it is first dreamt, discovered and invented. As the paper indicates in its final conclusions, to lose touch with this “otherness” is to lose something about leisure and living that is truly magical.</p

Autoinduction through the coupling of nucleation-dependent self-assembly of a supramolecular gelator and a reaction network.

 Autocatalytic and/or self-replicating systems are important aspects of understanding the link between living systems (origins of life) and chemical networks. As a result, many scientists around the world are attempting to better understand these phenomena by producing chemical networks and linking them to self-assembly and pathway complexity (systems chemistry). We present here a superficially autocatalytic, self-replicating system by utilising dynamic imine chemistry coupled with self-assembling supramolecular hydrogelation kinetics that is driven by a nucleation autocatalytic cycle (autoinduction). The dynamic nature of the imine bond within water allows “error checking” correction and driving of the imine equilibrium to starting materials but when coupled to the self-assembly gives rise to one reaction product from a possible thirteen intermediates and/or products (of a mixed four-step reaction). This product represents a thermodynamic minimum within the system's and reaction network's energy landscape. The self-assembly in solution of the replicator results in the formation of supramolecular polymers which would normally markedly reduce the catalytic efficiency of the system if a template mechanism of autocatalysis is in play. By overcoming the limiting effects of the self-assembly process it is possible to demonstrate exponential growth in replicator concentration once nucleation has occurred. It is only once the completed imine can undergo non-reversible tautomerisation that the product is prevented from reacting with water. We thus suggest that this sigmoidal kinetic characterisation is not inherent to autocatalysis kinetics (lowering reaction barriers and/or templating) but rather a result of the nucleation-based assembly allowing for intermediates to be prevented from reacting with water in a water-deficient environment (an autoinduction autocatalytic mechanism). Not only does this study provide a basis with which to explore aspects of self-replication connected with self-assembly, but also explores how nucleation and self-assembly growth can play a crucial role in self-replication. By controlling the kinetics of the autocatalytic chemical reaction at one end of the hierarchical assembly process we can influence the physical properties of the supramolecular gel at the other. This may have wide-ranging applications with in situ formed small molecular gelators where specific mechanical properties (rheology) are desired. </p

Exploring multi-couple field modelling and simulation for surface roughness in MRSTP of blade tenons using shear thickening effect and magnetohydrodynamics

Abstract Magnetorheological Shear Thickening Polishing (MRSTP) has emerged as a promising technique for achieving nano-level surface quality. This study investigates the dynamics of MRSTP applied to the complex geometries of turbine blade tenons, made of Inconel-718. A theoretical model was developed to predict surface roughness during MRSTP, by integrating experimental and simulation data. The model is based on surface generation principles and accounts for shape changes into a Gaussian cone during material removal. It integrates hydrodynamics, rheological properties of the MRSTP media, and magnetic field effects along with plastic indentation theory. Computational fluid dynamics simulations were used to analyse wall shear stress, and results were incorporated into the theoretical model. A custom magnetic field generation device was designed and MRSTP media was prepared in-house. A series of MRSTP experiments were conducted to validate the model, measuring and analysing surface topographies to align with the proposed mechanism. The experimental validation revealed that the model accurately predicts transient roughness reduction with errors ranging from 4.2% to 7.9% for experimental results and 3.4% to 7.5% for theoretical to experimental errors. The MRSTP process effectively removed all scratches from the surface within 90 minutes, demonstrating substantial improvements in surface quality, reduced roughness, and emphasizing the need to adapt machining parameters for different materials.</p

Virtual reality in clinical and experimental gambling research a review of methodologies

A meta analysis reviewing the current data on Gambling VR methodologies. </p

Bishopscourt, Isle of Man: Historic Architecture & Decorative Interior

CONFIDENTIALThe report describes a series of studies undertaken to establish the sequence of buildings at Bishopscourt, their likely dates and the history of the decorative interiors. That work included a consideration of readily available topographical prints and drawings, an examination of published accounts and a study of the historic fabric. An archaeological study was made of the buildings to identify the main phases of construction, using both internal and external evidence. A study of 85 paint samples revealed the decorative history of the interior. All these studies were brought together to provide a preliminary summary account of the history of the buildings.</p

Prevalence, incidence, indication, and choice of antidepressants in patients with and without chronic kidney disease: a matched cohort study in UK Clinical Practice Research Datalink

Purpose: People with chronic kidney disease (CKD) have an increased prevalence of depression, anxiety, and neuropathic pain. We examined prevalence, incidence, indication for, and choice of antidepressants among patients with and without CKD. Methods: Using the UK Clinical Practice Research Datalink, we identified patients with CKD (two measurements of estimated glomerular filtration rate�<�60�mL/min/1.73m2 for ?3�months) between April 2004 and March 2014. We compared those with CKD to a general population cohort without CKD (matched on age, sex, general practice, and calendar time [index date]). We identified any antidepressant prescribing in the six months prior to index date (prevalence), the first prescription after index date among non-prevalent users (incidence), and recorded diagnoses (indication). We compared antidepressant choice between patients with and without CKD among patients with a diagnosis of depression. Results: There were 242�349 matched patients (median age 76 [interquartile range 70�82], male 39.3%) with and without CKD. Prevalence of antidepressant prescribing was 16.3 and 11.9%, and incidence was 57.2 and 42.4/1000 person-years, in patients with and without CKD, respectively. After adjusting for confounders, CKD remained associated with higher prevalence and incidence of antidepressant prescription. Regardless of CKD status, selective serotonin reuptake inhibitors were predominantly prescribed for depression or anxiety, while tricyclic antidepressants were prescribed for neuropathic pain or other reasons. Antidepressant choice was similar in depressed patients with and without CKD. Conclusions: The rate of antidepressant prescribing was nearly one and a half times higher among people with CKD than in the general population. � 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. � 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd</p

Comparative effectiveness of fourth-line anti-hypertensive agents in resistant hypertension: A systematic review and meta-analysis

Aim We assessed the effectiveness of fourth-line mineralocorticoid receptor antagonists in comparison with other fourth-line anti-hypertensive agents in resistant hypertension. Methods and results We systematically searched Medline, EMBASE and the Cochrane library from database inception until January 2016. We included randomised and non-randomised studies that compared mineralocorticoid receptor antagonists with other fourth-line anti-hypertensive agents in patients with resistant hypertension. The outcome was change in systolic blood pressure, measured in the office, at home or by ambulatory blood pressure monitoring. Secondary outcomes were changes in serum potassium and occurrence of hyperkalaemia. We used random effects models and assessed statistical heterogeneity using the I2 test and corresponding 95% confidence intervals. From 2,506 records, 5 studies met our inclusion criteria with 755 included patients. Two studies were randomised and three were non-randomised. Comparative fourth-line agents included bisoprolol, doxazosin, furosemide and additional blockade of the renin angiotensin-aldosterone system. Using data from randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 7.4 mmHg (95%CI 3.2 - 11.6) more than the active comparator. When limited to non-randomised studies, mineralocorticoid receptor antagonists reduced blood pressure by 11.9 mmHg (95% CI 9.3 - 14.4) more than the active comparator. Conclusion On the basis of this meta-analysis, mineralocorticoid receptor antagonists reduce blood pressure more effectively than other fourth-line agents in resistant hypertension. Effectiveness stratified by ethnicity and comorbidities, in addition to information on clinical outcomes such as myocardial infarction and stroke, now needs to be determined. � European Society of Cardiology.</p