Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Involving decision-makers in the transformation of results into urban sustainability policies

Mind mapping tools are used to stimulate thinking about sustainability and define its significance for urban planning. Such tools are based on keywords that are identified and structured through dialogue-based procedures. The approach can be used also for switching between highlighting sectorial aspects, such as territorial management and urban design, social and economic cohesion and cross-sectorial aspects, such as sustainable mobility and energy efficiency. This paper emphasizes a structured dialogue with desicion-makers at national, regional and local levels, aimed at identifying what decision-makers really need to decide and the key barriers to the implementation of existing urban sustainability tools. This study was organized in four discrete steps. Initially, what EU urban sustainability projects can deliver (studies, methodologies, tools, policies, etc.) was identified. The deliverables were evaluated against certain criteria and categorized into cross-cutting aspects (territorial management and urban design, social and economic cohesion) and sectorial aspects (sustainable mobility, energy efficiency). The structured dialogue was implemented in parallel with the evaluation of the deliverables in order to match them with decision-makers’ needs, priorities and expectations. The ultimate goal was to develop and make available an operational Decision Support System (DSS) for public Authorities and urban planners, which combines their needs, priorities and expectations (structured dialogue results) with existing deliverables, developed within the framework of EU projects that up to now have had a low transferability and applicability rate

Preservation of the Mediterranean Identity: An Intra-City Analysis Towards a Macro-Regional Approach for the Characterisation of Urban Sustainability

Globalisation combined with high urbanisation trends affects not only the traditional pillars of sustainability (environment, society, and economy), but also local identity. Customs and traditions are fading away and alienation is the result of new lifestyles deriving mainly from high interaction between locals and foreigners (focus on tourism). Facing the challenge of characterising urban sustainability, reflection on special characteristics of the urban fabric that are affected (spatial dimension of sustainability) is not always considered. Even though a lot of research is dedicated to the characterisation of urban areas&rsquo; sustainability, the element of local, regional, and macro-regional identity seems not to be systematically incorporated. This work attempts to develop and test a methodological framework to identify and prioritise the common symbolic elements that constitute the identity of a group of cities and that need to be sustained. The study focuses on the Euro-Mediterranean region. A survey is addressed to 64 scientists from five cities: Dubrovnik, Genoa, Rhodes, Valencia, and Venice. &ldquo;Urban structure&rdquo; is revealed as the most important element that constitutes the &ldquo;Mediterranean identity&rdquo;. Moreover, the level of threat deriving from mass tourism on the &ldquo;Mediterranean identity&rdquo; is estimated. The survey provides insight into the definition of the spatial dimension of sustainability and the determination/weighting of the case-specific component of an integrated urban sustainability assessment tool

Decision Support System to Implement Units of Alternative Biowaste Treatment for Producing Bioenergy and Boosting Local Bioeconomy

Lately, the model of circular economy has gained worldwide interest. Within its concept, waste is viewed as a beneficial resource that needs to be re-introduced in the supply chains, which also requires the use of raw materials, energy, and water to be minimized. Undeniably, a strong link exists between the bioeconomy, circular economy, bioproducts, and bioenergy. In this light, in order to promote a circular economy, a range of alternative options and technologies for biowaste exploitation are currently available. In this paper, we propose a generic methodological scheme for the development of small, medium, or large-scale units of alternative biowaste treatment, with an emphasis on the production of bioenergy and other bioproducts. With the use of multi-criteria decision analysis, the model simultaneously considers environmental, economic, and social criteria to support robust decision-making. In order to validate the methodology, the latter was demonstrated in a real-world case study for the development of a facility in the region of Serres, Greece. Based on the proposed methodological scheme, the optimal location of the facility was selected, based on its excellent assessment in criteria related to environmental performance, financial considerations, and local acceptance. Moreover, anaerobic digestion of agricultural residues, together with farming and livestock wastes, was recommended in order to produce bioenergy and bioproducts

Delaying surgery for patients with a previous SARS-CoV-2 infection

Not availabl