BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Colour ConText

For several centuries, the literature of artists’ recipe books has been considered one of the most original and comprehensive primary sources for the historical study of artistic practices and materials. In addition to the famous Libro dell’arte of Cennino Cennini, nearly five hundred European manuscripts containing artistic recipes survive from before circa 1550. A great number of these are still unpublished and virtually unknown. Our work on a large corpus of recipe collections has generated the material for a database that facilitates consultation and exploitation of the source material.Current structure of the database The core data consists of mediaeval and pre-modern manuscripts and printed books from Northern and Southern Europe. The various layouts of the ‘Colour ConText’ database allow access to the metadata of the sources with details such as title, current location, place and date of origin, scribes or authors, previous owners, and description of any other (non-recipe) content. The database also allows access to digital images of these sources via European Cultural Heritage Online (ECHO) or via digital collections made available by external institutes, and to the transcription and translation of the recipe texts. Reference to primary and secondary sources, together with the related bibliographical data, is integrated throughout the database. To date, over 400 manuscripts have been considered and 4,500 recipes - some constituting only a few lines, others covering several folios - have been transcribed and recorded within the database. The database also includes a complete index of the ‘simples’ (substances mentioned as ingredients). Thus materials are indexed both by their current scientific name and by the terms exactly as they appear in the source texts. Each ingredient’s appellation is linked by relational tables to its contemporary and modern synonyms. This allows the retrieval of all the different appellations used for one ingredient – detailing the historical written context – but also the various ingredients that may be related to one ‘appellation’. A survey of artistic materials and techniques The database helps not only to observe the global frequency and recurrence of each ingredient and technical instruction, but also to deduce the availability of artistic material within a chronologically and geographically defined area. Many of these recipes can be used to identify specific, datable practices and materials, as compilers often specify the name and/or place of origin of the artists from whom they obtained their information. Information related to the historical provenance of the source material (obtained through codicological or philological analysis) has also been recorded within the database and may be used for that purpose. Moreover, it is possible to observe, through factors such as frequency within the corpus, basic structure, and evolution, how recipes were modified over time or by other external phenomena. It is also possible to link the development of specific artistic procedures and technical traditions, and to correlate these with more widely diffused techniques. Thus, recipe books allow us to study the geography, chronology, circulation and dissemination of artists’ knowledge. Colour material and terminology This project notably aims at considering and evaluating the importance and interest accorded to knowledge of the materials and substances used by artists and shared with other professionals (such as apothecaries), focusing on pigments and colouring material. For that purpose, other written sources related to colour will be included (notably texts on colour theory, on colour symbolism, on colour systems, on the pharmaceutical qualities of colours, etc.). In parallel to the physical descriptions of pigments and colourants, these written sources deliver information concerning their optical characteristics, conservation, (in)compatibility with other sorts of materials and their ageing properties. The diversity of colour denominations and the complexity of the varied technical terminology will be made transparent through a glossary of all the substances, ingredients, and their synonyms mentioned in the recipe books. Transmission of artists’ knowledge Such collections of recipes were often gathered in the same book with other subjects (such as theology, alchemy, botany or medicine) and these are also described within the database. The database also includes information concerning the provenance and circulation of these books outside the workshop. This allows other questions to be addressed - notably those related to the ownership and readership of collections of recipes

Understanding Monastic Practices of Oral Communication (Western Europe, Tenth-thirteenth Centuries), edited by Steven Vanderputten, Brepols, Turnhout 2011 (Utrecht Studies in Medieval Literacy, 21)

peer reviewe