Polymorphisms in the ATG16L1 Gene are associated with psoriasis vulgaris

Letter to the Edito

Absolute Present, Zen and Schrödinger’s One Mind

Erwin Schrödinger holds a prominent place in the history of science primarily due to his crucial role in the development of quantum physics. What is perhaps lesser known are his insights into subject-object duality, consciousness and mind. He documented himself that these were influenced by the Upanishads, a collection of ancient Hindu spiritual texts. Central to his thoughts in this area is that Mind is only One and there is no separation between subject and object. This chapter aims to bridge Schrödinger’s view on One Mind with the teachings of Dōgen, a twelfth century Zen master. This bridge is formed by addressing the question of how time relates to One Mind, and subject-object duality. Schrödinger describes the experience of One Mind to be like a timeless now, whereas subject-object duality involves a linear continuum of time. We show how these differing positions are unified in the notion of ‘absolute present’, which was put forward in the philosophy of Nishida Kitarō (1871–1945). In addition, we argue that it is in this notion of absolute present that the views of Schrödinger, Dōgen and Nishida meet

Data driven model for heat load prediction in buildings connected to District Heating by using smart heat meters

[EN] An accurate characterization and prediction of heat loads in buildings connected to a District Heating (DH) network is crucial for the effective operation of these systems. The high variability of the heat production process of DH networks with low supply temperatures and derived from the incorporation of different heat sources increases the need for heat demand prediction models. This paper presents a novel data-driven model for the characterization and prediction of heating demand in buildings connected to a DH network. This model is built on the so-called Q-algorithm and fed with real data from 42 smart energy meters located in 42 buildings connected to the DH in Tartu (Estonia). These meters deliver heat consumption data with a 1-h frequency. Heat load profiles are analysed, and a model based on supervised clustering methods in combination with multiple variable regression is proposed. The model makes use of four climatic variables, including outdoor ambient temperature, global solar radiation and wind speed and direction, combined with time factors and data from smart meters. The model is designed for deployment over large sets of the building stock, and thus aims to forecast heat load regardless of the construction characteristics or final use of the building. The low computational cost required by this algorithm enables its integration into machines with no special requirements due to the equations governing the model. The data-driven model is evaluated both statistically and from an engineering or energetic point of view. R-2 values from 0.70 to 0.99 are obtained for daily data resolution and R-2 values up to 0.95 for hourly data resolution. Hourly results are very promising for more than 90% of the buildings under study. (This study has been carried out in the context of RELaTED project. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 768567. This publication reflects only the authors' views and neither the Agency nor the Commission are responsible for any use that may be made of the information contained therein

Seven days treatment with the angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients; a placebo-controlled randomised multi-centre double-blind phase 2 trial

Background: COVID-19 morbidity and mortality remains high and the need for safe and effective drugs continues despite vaccines. Methods: Double-blind, placebo-controlled, multi-centre, randomised, parallel group phase 2 trial to evaluate safety and efficacy of oral angiotensin II type 2 receptor agonist C21 in hospitalized patients with COVID-19 and CRP ≥ 50-150 mg/L conducted at eight sites in India (NCT04452435). Patients were randomly assigned 100 mg C21 bid or placebo for 7 days in addition to standard of care. Primary endpoint: reduction in CRP. The study period was 21 July to 13 October 2020. Findings: 106 patients were randomised and included in the analysis (51 C21, 55 placebo). There was no significant group difference in reduction of CRP, 81% and 78% in the C21 and placebo groups, respectively, with a treatment effect ratio of 0.85 [90% CI 0.57, 1.26]. In a secondary analysis in patients requiring supplemental oxygen at randomisation, CRP was reduced in the C21 group compared to placebo. At the end of the 7-day treatment, 37 (72.5%) and 30 (54.5%) of the patients did not require supplemental oxygen in the C21 and placebo group, respectively (OR 2.20 [90% CI 1.12, 4.41]). A post hoc analysis showed that at day 14, the proportion of patients not requiring supplemental oxygen was 98% and 80% in the C21 group compared to placebo (OR 12.5 [90% CI 2.9, 126]). Fewer patients required mechanical ventilation (one C21 patient; four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one vs three in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated. Interpretation: Among hospitalised patients with COVID-19 receiving C21 for 7 days there was no reduction in CRP compared to placebo. However, a post-hoc analysis indicated a marked reduction of requirement for oxygen at day 14. The day 14 results from this study justify further evaluation in a Phase 3 study and such a trial is currently underway. Funding: Vicore Pharma AB and LifeArc, UK

Wfs1-deficient mice display altered function of serotonergic system and increased behavioral response to antidepressants

It has been shown that mutations in the WFS1 gene make humans more susceptible to mood disorders. Besides that, mood disorders are associated with alterations in the activity of serotonergic and noradrenergic systems. Therefore, in this study, the effects of imipramine, an inhibitor of serotonin (5-HT) and noradrenaline (NA) reuptake, and paroxetine, a selective inhibitor of 5-HT reuptake, were studied in tests of behavioral despair. The tail suspension test (TST) and forced swimming test (FST) were performed in Wfs1-deficient mice. Simultaneously, gene expression and monoamine metabolism studies were conducted to evaluate changes in 5-HT- and NA-ergic systems of Wfs1-deficient mice. The basal immobility time of Wfs1-deficient mice in TST and FST did not differ from that of their wild-type littermates. However, a significant reduction of immobility time in response to lower doses of imipramine and paroxetine was observed in homozygous Wfs1-deficient mice, but not in their wild-type littermates. In gene expression studies, the levels of 5-HT transporter (SERT) were significantly reduced in the pons of homozygous animals. Monoamine metabolism was assayed separately in the dorsal and ventral striatum of naive mice and mice exposed for 30 min to brightly lit motility boxes. We found that this aversive challenge caused a significant increase in the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-HT, in the ventral and dorsal striatum of wild-type mice, but not in their homozygous littermates. Taken together, the blunted 5-HT metabolism and reduced levels of SERT are a likely reason for the elevated sensitivity of these mice to the action of imipramine and paroxetine. These changes in the pharmacological and neurochemical phenotype of Wfs1-deficient mice may help to explain the increased susceptibility of Wolfram syndrome patients to depressive states

'You were quiet - I did all the marching': Research processes involved in hearing the voices of South Asian girls

This article is available open access through the publisher’s website at the link below. Copyright @ 2011 A B Academic Publishers.This article provides insights into the outcomes of reflection following two interview approaches used to explore narratives of the lived, individual experiences of South-Asian girls living in West London. In attempting to illuminate and re-present the cultural experiences as told by these girls, the choice of interview approach became critical in allowing the voices to be effectively heard (Rogers, 2005). This article therefore considers how a semi-structured interview approach offered valuable insights into the girls' experiences but became constraining for both researcher and participant in unveiling the complexity and depth of their lives. These constraints emerged through reflection by both participants and researcher. As a result of reflexivity during the research process, the researcher moved towards the use of research conversations during the second phase of the study. Ultimately the study revealed how the girls felt empowered by the opportunity to narrate their individual experiences and tell of their lives. In narrating their reflections on being part of the research, there was a clear recognition that the process facilitated the articulation of new voices and ‘multi-voicedness’ (Moen, 2006

Women's knowledge about cervical cancer risk factors, screening, and reasons for non-participation in cervical cancer screening programme in Estonia

<p>Abstract</p> <p>Background</p> <p>The attendance rate in Estonian cervical cancer screening programme is too low therefore the programme is hardly effective. A cross-sectional population based survey was performed to identify awareness of cervical cancer risk factors, reasons why women do not want to participate in cervical screening programme and wishes for better organisation of the programme.</p> <p>Method</p> <p>An anonymous questionnaire with a covering letter and a prepaid envelope was sent together with the screening invitation to 2942 randomly selected women. Results are based on the analysis of 1054 (36%) returned questionnaires.</p> <p>Results</p> <p>Main reasons for non-participation in the national screening programme were a recent visit to a gynaecologist (42.3%), fear to give a Pap-smear (14.3%), long appointment queues (12.9%) and unsuitable reception hours (11.8%). Fear to give a Pap-smear was higher among women aged 30 and 35 than 50 and 55 (RR 1.46; 95% CI: 0.82-2.59) and women with one or no deliveries (RR 1.56, 95% CI: 0.94-2.58). In general, awareness of cervical cancer risk factors is poor and it does not depend on socio-demographic factors. Awareness of screening was higher among Estonians than Russians (RR 1.64, 95% CI: 1.46-1.86). Most women prefer to receive information about screening from personally mailed invitation letters (74.8%).</p> <p>Conclusions</p> <p>Women need more information about cervical cancer risk factors and the screening programme. They prefer personally addressed information sharing. Minority groups should be addressed in their own language. A better collaboration with service providers and discouraging smears outside the programme are also required.</p

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited