Evaluation of simulated responses to climate forcings: a flexible statistical framework using confirmatory factor analysis and structural equation modelling – Part 2: Numerical experiment

The performance of a new statistical framework, developed for the evaluation of simulated temperature responses to climate forcings against temperature reconstructions derived from climate proxy data for the last millennium, is evaluated in a so-called pseudo-proxy experiment, where the true unobservable temperature is replaced with output data from a selected simulation with a climate model. Being an extension of the statistical model used in many detection and attribution (D&amp;A) studies, the framework under study involves two main types of statistical models, each of which is based on the concept of latent (unobservable) variables: confirmatory factor analysis (CFA) models and structural equation modelling (SEM) models. Within the present pseudo-proxy experiment, each statistical model was fitted to seven continental-scale regional data sets. In addition, their performance for each defined region was compared to the performance of the corresponding statistical model used in D&amp;A studies. The results of this experiment indicated that the SEM specification is the most appropriate one for describing the underlying latent structure of the simulated temperature data in question. The conclusions of the experiment have been confirmed in a cross-validation study, presuming the availability of several simulation data sets within each studied region. Since the experiment is performed only for zero noise level in the pseudo-proxy data, all statistical models, chosen as final regional models, await further investigation to thoroughly test their performance for realistic levels of added noise, similar to what is found in real proxy data for past temperature variations.</p

New kid on the ID block: Neural functions of the Nab2/ZC3H14 class of Cys3His tandem zinc-finger polyadenosine RNA binding proteins

Polyadenosine RNA binding proteins (Pabs) play critical roles in regulating the polyadenylation, nuclear export, stability, and translation of cellular RNAs. Although most Pabs are ubiquitously expressed and are thought to play general roles in post-transcriptional regulation, mutations in genes encoding these factors have been linked to tissue-specific diseases including muscular dystrophy and now intellectual disability (ID). Our recent work defined this connection to ID, as we showed that mutations in the gene encoding the ubiquitously expressed Cys3His tandem zinc-finger (ZnF) Pab, ZC3H14 (Zinc finger protein, CCCH-type, number 14) are associated with non-syndromic autosomal recessive intellectual disability (NS-ARID). This study provided a first link between defects in Pab function and a brain disorder, suggesting that ZC3H14 plays a required role in regulating RNAs in nervous system cells. Here we highlight key questions raised by our study of ZC3H14 and its ortholog in the fruit fly Drosophila melanogaster, dNab2, and comment on future approaches that could provide insights into the cellular and molecular roles of this class of zinc finger-containing Pabs. We propose a summary model depicting how ZC3H14-type Pabs might play particularly important roles in neuronal RNA metabolism

Evaluation of simulated responses to climate forcings: a flexible statistical framework using confirmatory factor analysis and structural equation modelling – Part 1: Theory

Evaluation of climate model simulations is a crucial task in climate research. Here, a new statistical framework is proposed for evaluation of simulated temperature responses to climate forcings against temperature reconstructions derived from climate proxy data for the last millennium. The framework includes two types of statistical models, each of which is based on the concept of latent (unobservable) variables: confirmatory factor analysis (CFA) models and structural equation modelling (SEM) models. Each statistical model presented is developed for use with data from a single region, which can be of any size. The ideas behind the framework arose partly from a statistical model used in many detection and attribution (D&amp;A) studies. Focusing on climatological characteristics of five specific forcings of natural and anthropogenic origin, the present work theoretically motivates an extension of the statistical model used in D&amp;A studies to CFA and SEM models, which allow, for example, for non-climatic noise in observational data without assuming the additivity of the forcing effects. The application of the ideas of CFA is exemplified in a small numerical study, whose aim was to check the assumptions typically placed on ensembles of climate model simulations when constructing mean sequences. The result of this study indicated that some ensembles for some regions may not satisfy the assumptions in question.</p

Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients?

Objectives Based on its well-documented anti-inflammatory and restorative properties we propose trials with the natural hormone oxytocin for treatment of hospitalised Covid-19 patients. Methods We searched for, retrieved, and commented on specific literature regarding multiple functions of oxytocin with a special focus on its modulation of inflammatory, immune, and restorative functions. Results Available data gathered in animals and humans support the anti-inflammatory properties of oxytocin. The multiple anti-inflammatory effects of oxytocin have been demonstrated in vitro and in vivo in various animal models and also in humans in response to intravenous infusion of oxytocin. Furthermore, oxytocin has been documented to activate several types of protective and restorative mechanisms and to exert positive effects on the immune system. Conclusions In addition, to being anti-inflammatory, it may be hypothesised, that oxytocin may be less suppressive on adaptive immune systems, as compared with glucocorticoids. Finally, by its restorative effects coupled with its anti-stress and healing properties, oxytocin may shorten the recovery period of the Covid-19 patients

Transnational reflections on transnational research projects on men, boys and gender relations

This article reflects on the research project, ‘Engaging South African and Finnish youth towards new traditions of non-violence, equality and social well-being’, funded by the Finnish and South African national research councils, in the context of wider debates on research, projects and transnational processes. The project is located within a broader analysis of research projects and projectization (the reduction of research to separate projects), and the increasing tendencies for research to be framed within and as projects, with their own specific temporal and organizational characteristics. This approach is developed further in terms of different understandings of research across borders: international, comparative, multinational and transnational. Special attention is given to differences between research projects that are in the Europe and the EU, and projects that are between the global North and the global South. The theoretical, political and practical challenges of the North-South research project are discussed

Analytical considerations in deriving 99th percentile upper reference limits for high-sensitivity cardiac troponin assays: Educational recommendations from the IFCC committee on clinical application of cardiac bio-markers

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee’s goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.publishedVersio

EQ-5D in skin conditions: an assessment of validity and responsiveness

Aims and objectives This systematic literature review aims to assess the reliability, validity and responsiveness of three widely used generic preference-based measures of health-related quality of life (HRQL), i.e., EQ-5D, Health Utility Index 3 (HUI3) and SF-6D in patients with skin conditions. Methods A systematic search was conducted to identify studies reporting health state utility values obtained using EQ-5D, SF-6D, or HUI3 alongside other HRQL measures or clinical indices for patients with skin conditions. Data on test-retest analysis for reliability, known group differences or correlation and regression analyses for validity, and change over time or responsiveness indices analysis were extracted and reviewed. Results A total of 16 papers reporting EQ-5D utilities in people with skin conditions were included in the final review. No papers for SF-6D and HUI3 were found. Evidence of reliability was not found for any of these measures. The majority of studies included in the review (12 out of 16) examined patients with plaque psoriasis or psoriatic arthritis and the remaining four studies examined patients with either acne, hidradenitis suppurativa, hand eczema, or venous leg ulcers. The findings were generally positive in terms of performance of EQ-5D. Six studies showed that EQ-5D was able to reflect differences between severity groups and only one reported differences that were not statistically significant. Four studies found that EQ-5D detected differences between patients and the general population, and differences were statistically different for three of them. Further, moderate-to-strong correlation coefficients were found between EQ-5D and other skin-specific HRQL measures in four studies. Eight studies showed that EQ-5D was able to detect change in HRQL appropriately over time and the changes were statistically significant in seven studies. Conclusions Overall, the validity and responsiveness of the EQ-5D was found to be good in people with skin diseases, especially plaque psoriasis or psoriatic arthritis. No evidence on SF-6D and HUI3 was available to enable any judgments to be made on their performance

Jejunal perforation in gallstone ileus – a case series

<p>Abstract</p> <p>Introduction</p> <p>Gallstone ileus is an uncommon complication of cholelithiasis but an established cause of mechanical bowel obstruction in the elderly. Perforation of the small intestine proximal to the obstructing gallstone is rare, and only a handful of cases have been reported. We present two cases of perforation of the jejunum in gallstone ileus, and remarkably in one case, the gallstone ileus caused perforation of a jejunal diverticulum and is to the best of our knowledge the first such case to be described.</p> <p>Case presentations</p> <p><b>Case 1</b></p> <p>A 69 year old man presented with two days of vomiting and central abdominal pain. He underwent laparotomy for small bowel obstruction and was found to have a gallstone obstructing the mid-ileum. There was a 2 mm perforation in the anti-mesenteric border of the dilated proximal jejunum. The gallstone was removed and the perforated segment of jejunum was resected.</p> <p><b>Case 2</b></p> <p>A 68 year old man presented with a four day history of vomiting and central abdominal pain. Chest and abdominal radiography were unremarkable however a subsequent CT scan of the abdomen showed aerobilia. At laparotomy his distal ileum was found to be obstructed by an impacted gallstone and there was a perforated diverticulum on the mesenteric surface of the mid-jejunum. An enterolithotomy and resection of the perforated small bowel was performed.</p> <p>Conclusion</p> <p>Gallstone ileus remains a diagnostic challenge despite advances in imaging techniques, and pre-operative diagnosis is often delayed. Partly due to the elderly population it affects, gallstone ileus continues to have both high morbidity and mortality rates. On reviewing the literature, the most appropriate surgical intervention remains unclear.</p> <p>Jejunal perforation in gallstone ileus is extremely rare. The cases described illustrate two quite different causes of perforation complicating gallstone ileus. In the first case, perforation was probably due to pressure necrosis caused by the gallstone. The second case was complicated by the presence of a perforated jejunal diverticulum, which was likely to have been secondary to the increased intra-luminal pressure proximal to the obstructing gallstone.</p> <p>These cases should raise awareness of the complications associated with both gallstone ileus, and small bowel diverticula.</p

How much synthetic oxytocin is infused during labour? A review and analysis of regimens used in 12 countries.

OBJECTIVE: To compare synthetic oxytocin infusion regimens used during labour, calculate the International Units (IU) escalation rate and total amount of IU infused over eight hours. DESIGN: Observational study. SETTING: Twelve countries, eleven European and South Africa. SAMPLE: National, regional or institutional-level regimens on oxytocin for induction and augmentation labour. METHODS: Data on oxytocin IU dose, infusion fluid amount, start dose, escalation rate and maximum dose were collected. Values for each regimen were converted to IU in 1000ml diluent. One IU corresponded to 1.67μg for doses provided in grams/micrograms. IU hourly dose increase rates were based on escalation frequency. Cumulative doses and total IU amount infused were calculated by adding the dose administered for each previous hour. Main Outcome Measures Oxytocin IU dose infused. RESULTS: Data were obtained on 21 regimens used in 12 countries. Details on the start dose, escalation interval, escalation rate and maximum dose infused were available from 16 regimens. Starting rates varied from 0.06 IU/hour to 0.90 IU/hour, and the maximum dose rate varied from 0.90 IU/hour to 3.60 IU/hour. The total amount of IU oxytocin infused, estimated over eight hours, ranged from 2.38 IU to 27.00 IU, a variation of 24.62 IU and an 11-fold difference. CONCLUSION: Current variations in oxytocin regimens for induction and augmentation of labour are inexplicable. It is crucial that the appropriate minimum infusion regimen is administered because synthetic oxytocin is a potentially harmful medication with serious consequences for women and babies when inappropriately used. Estimating the total amount of oxytocin IU received by labouring women, alongside the institution's mode of birth and neonatal outcomes, may deepen our understanding and be the way forward to identifying the optimal infusion regimen

Barriers, emotions, and motivational levers for lifestyle transformation in Norwegian household decarbonization pathways

Meeting the Paris Agreement targets requires strong near-term climate change mitigation in all sectors of the economy. Increasing demand-side emission abatement efforts is one important area to pursue, yet there are significant barriers that must be overcome in order to realize its potential. We ask: What barriers may be hindering deep emissions reduction at the household level? What kinds of levers are available to achieve emission reductions? Based on an original and extensive qualitative dataset, our in-depth study of households in Bergen, Norway, shows that individuals perceive they are confronted with considerable individual, economic, and infrastructural barriers that prevent them from taking deep mitigation actions. Our results however also suggest that some barriers can be overcome with motivational levers such as the availability of more sustainable alternatives, support networks and by the positive emotions felt when having a positive impact on the environment. Other barriers are more difficult to overcome, pointing to the overarching lesson from our study that households will need to be forced or incentivized beyond voluntary efforts to achieve rapid and comprehensive decarbonization. The current policy approach, aimed mostly at nudging for voluntary mitigation actions, is wholly inadequate to achieve significant emission reductions. Our study indicates that households are open for increasingly including more “sticks” into climate policymaking. While there are significant challenges to individuals taking stronger mitigation action, these can be overcome by strengthening government policies targeting the patterns and, importantly, volumes of household consumption