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Prostate cancer is the commonest cancer in men in Europe and many countries worldwide, and the second commonest cause of cancer-related death. A screening programme to detect clinically relevant prostate cancer at a time when it can be cured, without burdensome overdiagnosis and subsequent overtreatment, is a laudable goal. We will set out the advances in MRI imaging, and the progress in MRI for men prior to biopsy, discussing whether MRI has a place before biopsy, or as a primary screening tool, in a modern approach to prostate cancer screening. [ABSTRACT FROM AUTHOR]

This article asks: what is the significance of design history within higher education? It reviews the practice and purpose of design history, in the education of historically aware and critically engaged designers, as an emerging independent discipline, and in terms of what the subject has to offer allied fields such as history, sociology, cultural studies, history of technology, area studies and anthropology. It considers the development and current state of design history as it is taught in the UK and non-Anglophone Europe (including France, Italy, Scandinavia, Spain, Turkey and Greece), in the US, Australia and East Asia. The argument that follows is grounded in recent design historical scholarship, combined with the views of design historians working in the abovementioned countries, in order to provide both a contemporary perspective on current practice and suggestions about possible futures. [ABSTRACT FROM PUBLISHER]

This study was focused on the evaluation of the microbiological indices, defined by European legislation, before and after the depuration of clams ( Chamelea gallina) landed in category B seawater. The survival of depurated clams and the meat yield were also evaluated. The results obtained from October 2002 to September 2003 evidenced a mean microbial reduction during depuration of 62% for Escherichia coli and 54% for fecal coliforms (FC). All the samples had FC counts below the limit after 24 h depuration with the exception of the August samples. E. coli was found in concentration slightly higher than the legal limit only in the samples of December and January. In August, the E. coli concentration did not decrease during the depuration, while in the other samples significant reduction of E. coli concentration was observed. Salmonella spp. and V. parahaemolyticus were never detected in the clams harvested between March and September. Vibrio alginolyticus was found in the clams harvested in May and September both before and after the depuration process. The viability of clam was not negatively affected by depuration, in fact, an increase of viability was observed with the exception of the samples of April. The meat yield was not influenced by the depurative treatment in C. gallina; the mean value found before depuration, 10.47% (with 1.95 SD), did not significantly vary after the treatment (10.58%, SD 2.07). In conclusion, the depuration conditions can improve the quality of C. gallina; however, its effects on microbiological quality depended on environmental conditions. [ABSTRACT FROM AUTHOR]

Abstract: Background: Unsedated transnasal oesogastroduodenoscopy significantly improves patient tolerance compared to unsedated conventional peroral oesogastroduodenoscopy. Aims: To assess the adoption of transnasal oesogastroduodenoscopy among endoscopists from various European countries and its determinants. Methods: A survey was distributed to 624 endoscopists attending a live course on digestive endoscopy; a poll was also performed immediately before and after live video retransmission of a transnasal oesogastroduodenoscopy. Results: Answer rate was 48%; transnasal oesogastroduodenoscopy was practised by 31% of respondents. In multivariate analysis, practice of transnasal oesogastroduodenoscopy was associated with location in France and Netherlands (P <0.0001), availability of many gastroscopes (P <0.0001) and less frequent use of sedation (P =0.006). Endoscopists who did not practise transnasal oesogastroduodenoscopy cited doubts about its advantages over conventional oesogastroduodenoscopy and lack of training (34% each) as barriers to adoption. Seventy-four percent of endoscopists practicing transnasal oesogastroduodenoscopy did actually use it in <20% of eligible cases. Live video retransmission of a transnasal oesogastroduodenoscopy increased the proportion of endoscopists interested in this technique (P =0.006). Conclusions: Adoption of transnasal oesogastroduodenoscopy largely varies between European countries; endoscopists practicing this technique use it in a minority of eligible cases. Live case demonstration may decrease barriers to the adoption of this technique. [Copyright &y& Elsevier]

Purpose - The main features of evolvable systems include distributed control, a modularized, intelligent and open architecture, a comprehensive and multi-dimensional methodological support that comprises the reference architecture. Furthermore, integration of legacy subsystems and modules has been addressed in the methodology. This paper aims to present the latest developments, applications and conclusions drawn to date. Design/methodology/approach - Evolvable assembly system is a new methodology in itself, and is currently being applied within several European projects. Evolvable assembly goes beyond reconfigurability and offers continuous evolution of the system. Findings - The work has been, and is being, implemented through large European research projects. Evolvability, being a system concept, is envisaged addressing every aspect of an assembly system throughout its life cycle, i.e. design and development, operation and evolution. Research limitations/implications - This paper presents the latest developments, applications and conclusions drawn to date. Originality/value - The paper presents the methodology and the latest application of it, which is industrial. This is the first application that offers self-configuration of the equipment. [ABSTRACT FROM AUTHOR]

The phytohormone auxin is involved in almost every process of a plant's life, from germination to plant development. Nowadays, auxin research connects synthetic chemistry, plant biology and computational chemistry in order to develop innovative and safe compounds to be used in sustainable agricultural practice. In this framework, we developed new fluorescent compounds, ethanolammonium p-aminobenzoate (HEA-pABA) and p-nitrobenzoate (HEA-pNBA), and investigated their auxin-like behavior on two main commercial vegetables cultivated in Europe, cucumber (Cucumis sativus) and tomato (Solanumlycopersicum), in comparison to the model plant Arabidopsis (Arabidopsis thaliana). Moreover, the binding modes and affinities of two organic salts in relation to the natural auxin indole-3-acetic acid (IAA) into TIR1 auxin receptor were investigated by computational approaches (homology modeling and molecular docking). Both experimental and theoretical results highlight HEA-pABA as a fluorescent compound with auxin-like activity both in Arabidopsis and the commercial cucumber and tomato. Therefore, alkanolammonium benzoates have a great potential as promising sustainable plant growth stimulators to be efficiently used in vegetable crops. [ABSTRACT FROM AUTHOR]

Background and Aims: Although much has been written about the conventional cardiovascular risk factor correlates of the extent of coronary artery calcification (CAC), few studies have been carried out on symptomatic patients. This paper assesses the potential ability of risk factors to associate with an increasing CAC score.Methods: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had conventional cardiovascular risk factor assessment and CT scanning for CAC scoring.Results: Among all patients, male sex (OR = 4.85, p<0.001) and diabetes (OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with age, hypertension, dyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p<0.001 for both). These results were echoed in quantile regression, where diabetes was consistently the most important correlate with CAC extent in every quantile in both males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively.Conclusion: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes. [ABSTRACT FROM AUTHOR]

In the last decades, the demand for air conditioning and cooling systems for buildings continues to increase, despite the awareness campaigns and the Green Policies adopted by European Countries. The adoption of such policies is dictated by climate change, and by the will to reduce GHG emissions and increase the use of energy from renewable sources. Among all the different air conditioning systems, the split systems represent most Room Air Conditioners (RAC) units installed in Europe. Their integration with the buildings of historical centres is not successful due to the sound emissions of external units and their visual impact on buildings' facades. The acoustic and the visual impact are evaluated separately, by comparing the results of outdoor noise prediction models with noise limits levels at receivers or using local regulations. A virtual reality environment has been prepared to carry out a laboratory experiment to understand better how Air Conditioning (AC) split units affect the residents' overall perceptions. This paper investigates the combined (auditory and visual) impacts of installing external units of split systems on historical buildings' facades. By combining different Visual Aspects and Noise Levels, the noise annoyance and other perceptual attributes of the environment have been studied. Main conclusions suggest that visual elements more integrated on the façade of the historical building can help reduce the auditory and the visual impact of these elements. Moreover, well-integrated and pleasant elements led to a lower auditory perception of the loudness and noise annoyance than less integrated elements. [ABSTRACT FROM AUTHOR]

Four European Reference Networks (ERN-EYE, ERKNet, Endo-ERN, ERN-ITHACA) have teamed up to establish a consensus statement and recommendations for Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive ciliopathy with at least 26 genes identified to date. The clinical manifestations are pleiotropic, can be observed in utero and will progress with age. Genetic testing has progressively improved in the last years prompting for a revision of the diagnostic criteria taking into account clinical Primary and Secondary features, as well as positive or negative molecular diagnosis. This consensus statement also emphasizes on initial diagnosis, monitoring and lifelong follow-up, and symptomatic care that can be provided to patients and family members according to the involved care professionals. For paediatricians, developmental anomalies can be at the forefront for diagnosis (such as polydactyly) but can require specific care, such as for associated neuro developmental disorders. For ophthalmology, the early onset retinal degeneration requires ad hoc functional and imaging technologies and specific care for severe visual impairment. For endocrinology, among other manifestations, early onset obesity and its complications has benefited from better evaluation of eating behaviour problems, improved lifestyle programs, and from novel pharmacological therapies. Kidney and urinary track involvements warrants lifespan attention, as chronic kidney failure can occur and early management might improve outcome. This consensus recommends revised diagnostic criteria for BBS that will ensure certainty of diagnosis, giving robust grounds for genetic counselling as well as in the perspective of future trials for innovative therapies., Competing Interests: Competing interests The development of this work was made without external financial support from industries involved in the manufacturing of therapies for BBS. Competing interests of members of the guideline development group have been recorded in writing and addressed. HD has consulted for Novartis, Rhythm Pharmaceuticals, Jansen Pharmaceutical, GenSight Biologics and Sparing Vision. JK, DL, AG, MMVH and JM have consulted for Rhythm Pharmaceuticals. EVDA’s institute was the recipient of a research grant from Rhythm Pharmaceuticals. MC is a principal investigator for the RM-IMC-901 study (a Registry of Patients with Biallelic Proopiomelanocortin (POMC), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), or Leptin Receptor (LEPR) Deficiency Obesity, or Bardet-Biedl Syndrome (BBS), Treated with Setmelanotide) and received payments for lectures, expert testimony and consulting fees and study support from Rhythm Pharmaceuticals; MC also received payments for lectures from Canon Medical Systems. CB is the medical and managing director of Medizinische Genetik Mainz and Limbach Genetics. BPL has consulted for Novartis, Jansen Pharmaceutical, GenSight Biologics and Sparing Vision. CP has consulted for Rhythm Pharmaceuticals and Novo Nordisk. SR has consulted for Rhythm Pharmaceuticals, Sandoz and Novo Nordisk. MRL, PM, AV, GMB, MGP, FT, MFS, FS, AG, MZ, HM, AMVE, DM, AS, DV, have no competing interests to declare., (© 2024. The Author(s).)

Introduction: Non-statin therapy (NST) is used as second-line treatment when statin monotherapy is inadequate or poorly tolerated., Objective: To determine the association of NST with plaque composition, alone or in combination with statins, in patients undergoing coronary computed tomography angiography (coronary CTA)., Methods: From the multicenter CONFIRM registry, we analyzed individuals who underwent coronary CTA with known lipid-lowering therapy status and without prior coronary artery disease at baseline. We created a propensity score for being on NST, followed by stepwise multivariate linear regression, adjusting for the propensity score as well as risk factors, to determine the association between NST and the number of coronary artery segments with each plaque type (non-calcified (NCP), partially calcified (PCP) or calcified (CP)) and segment stenosis score (SSS)., Results: Of the 27,125 subjects in CONFIRM, 4,945 met the inclusion criteria; 371 (7.5%) took NST. At baseline, patients on NST had more prevalent risk factors and were more likely to be on concomitant cardiac medications. After multivariate and propensity score adjustment, NST was not associated with plaque composition: NCP (0.07 increase, 95% CI: -0.05, 0.20; p = 0.26), PCP (0.10 increase, 95% CI: -0.10, 0.31; p = 0.33), CP (0.18 increase, 95% CI: -0.10, 0.46; p = 0.21) or SSS (0.45 increase, 95% CI: -0.02,0.93; p = 0.06). The absence of an effect of NST on plaque type was not modified by statin use (p for interaction > 0.05 for all)., Conclusion: In this cross-sectional study, non-statin therapy was not associated with differences in plaque composition as assessed by coronary CTA., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: This study sought to describe the impact of statins on individual coronary atherosclerotic plaques., Background: Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear., Methods: We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications., Results: Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features were lower in lesions in statin-taking patients (0.49 ± 2.39% per year vs. 1.06 ± 2.42% per year and 0.9% per year vs. 1.6% per year, respectively; all p < 0.001). The rates of progression to >50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development., Conclusions: Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of coronary artery disease and management strategies have relied solely on the presence of diameter stenosis ≥50%. We assessed whether direct quantification of plaque burden (PB) and plaque characteristics assessed by coronary computed tomography angiography could provide additional value in terms of predicting rapid plaque progression., Methods and Results: From a 13-center, 7-country prospective observational registry, 1345 patients (60.4±9.4 years old; 57.1% male) who underwent repeated coronary computed tomography angiography >2 years apart were enrolled. For conventional angiographic analysis, the presence of stenosis ≥50%, number of vessel involved, segment involvement score, and the presence of high-risk plaque feature were determined. For quantitative analyses, PB and annual change in PB (△PB/y) in the entire coronary tree were assessed. Clinical outcomes (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were recorded. Rapid progressors, defined as a patient with ≥median value of △PB/y (0.33%/y), were older, more frequently male, and had more clinical risk factors than nonrapid progressors (all P <0.05). After risk adjustment, addition of baseline PB improved prediction of rapid progression to each angiographic assessment of coronary artery disease, and the presence of high-risk plaque further improved the predictive performance (all P <0.001). For prediction of adverse outcomes, adding both baseline PB and △PB/y showed best predictive performance (C statistics, 0.763; P <0.001)., Conclusions: Direct quantification of atherosclerotic PB in addition to conventional angiographic assessment of coronary artery disease might be beneficial for improving risk stratification of coronary artery disease., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02803411., (© 2018 American Heart Association, Inc.)

Background: Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use., Methods and Results: Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age-sex percentiles of segment involvement score (SIS) at each year of life (40-79 years). The relationship between SIS age-sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (≤50th, 51-75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age-sex percentiles were well fitted to second-order polynomial curves (men: R 2 =0.86±0.12; women: R 2 =0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ≤50th, 51-75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%-2.7%], 3.9% [95% confidence interval: 3.0%-5.1%], and 7.2% [95% confidence interval: 5.4%-9.6%] in ≤50th, 51-75th, and >75th SIS% groups, respectively; P <0.001). Adjusted MACE risk was significantly increased among patients in SIS% groups above the median compared with patients below the median (hazard ratio [95% confidence interval]: 1.9 [1.3-2.8] for 51-75th SIS% group and 3.4 [2.3-5.0] for >75th SIS% group; P <0.01 for both)., Conclusions: We have developed clinically pragmatic age- and sex-specific nomograms of CAD prevalence using coronary computed tomography angiography findings. Global plaque burden measured using SIS% is predictive of cardiac events independent of traditional risk assessment., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443637., (© 2017 American Heart Association, Inc.)

Studies examining coronary computed tomographic angiography (CCTA) have demonstrated increased mortality related to coronary artery disease (CAD) severity but are limited to relatively nondiverse ethnic populations. The aim of this study was to evaluate the prognostic significance of CAD on CCTA according to ethnicity for patients without previous CAD in a prospective international CCTA registry of 11 sites (7 countries) who underwent 64-slice CCTA from 2005 to 2010. CAD was defined as any coronary artery atherosclerosis and obstructive CAD as ≥50% stenosis. All-cause mortality and nonfatal myocardial infarction (MI) were assessed by ethnicity using Kaplan-Meier and Cox proportional hazards, controlling for baseline risk factors, medications, and revascularization. A total of 16,451 patients of mean age 58 years (55% men) were followed over a median of 2.0 years (interquartile range 1.4 to 3.2). Patients were 60.1% Caucasian, 34.4% East Asian, and 5.5% African. Death or MI occurred in 0.5% (38 of 7,109) among patients with no CAD, 1.6% (91 of 5,600) among those with nonobstructive CAD, and 3.8% (142 of 3,742) among those with ≥50% stenosis (p <0.001 among all groups). The annualized incidence of death or MI comparing obstructive to no obstructive CAD among Caucasians was 2.2% versus 0.7% (adjusted hazard ratio [aHR] 2.77, 95% confidence interval [CI] 1.73 to 4.43, p <0.001), among Africans 4.8% versus 1.1% (aHR 6.25, 95% CI 1.12 to 34.97, p = 0.037), and among East Asians 0.8% versus 0.1% (aHR 4.84, 95% CI 2.24 to 10.9, p <0.001). Compared to other ethnicities, East Asians had fewer than expected events (aHR 0.25, 95% CI 0.16 to 0.38, p <0.001). In conclusion, the presence and severity of CAD visualized by CCTA predict death or MI across 3 large ethnicities, whereas normal results on CCTA identify patients at very low risk., (Published by Elsevier Inc.)

Background and Objectives: The few existing studies of sexual dysfunction in women on hemodialysis are limited by small sample size. This large, cross-sectional study evaluated the prevalence and correlates of female sexual dysfunction in advanced kidney disease. DESIGN, SETTING, PARTICIPANTS, METHODS: A total of 1472 women with ESRD undergoing hemodialysis were recruited to a multinational, cross-sectional study conducted within a collaborative dialysis network in Europe and South America. Sexual dysfunction was identified by the Female Sexual Function Index. Correlates of self-reported sexual dysfunction were identified by regression analyses., Results: Of the 1472 women, 659 completed questionnaires (45%). More than half (362 of 659 [55%]) lived with a partner, and 232 of 659 (35%) reported being sexually active. Of these 659 respondents, 555 (84%) reported sexual dysfunction. Women with a partner (282 of 362 [78%]) were less likely to report sexual dysfunction than those without a partner (273 of 297 [92%]) (P<0.001). Sexual dysfunction was independently associated with age, depressive symptoms, less education, menopause, diabetes, and diuretic therapy. Nearly all women who were not wait-listed for a kidney transplant and were living without a partner (249 of 260 [96%]) reported sexual dysfunction. More than half (128 of 232 [55%]) of sexually active women reported sexual dysfunction, associated with age, depressive symptoms, menopause, low serum albumin, and diuretic therapy., Conclusions: This descriptive study suggests most women on hemodialysis experience sexual problems. Additional research on the relevance of sexual dysfunction to symptom burden and quality of life in these women is needed.

We recently reported that Swedish VH3-21-using chronic lymphocytic leukemia (CLL) patients showed restricted immunoglobulin gene features and poor prognosis despite VH mutation status. To investigate this further, we analyzed the VH and VL gene rearrangements in 90 VH3-21+ patients from Sweden, Germany, Italy, United States, Finland, and Australia and correlated these data with survival and other prognostic markers. Sixty-three percent exhibited mutated VH genes and 37% unmutated VH genes. Fifty (56%) patients displayed a short and homologous heavy-chain CDR3, many of these with the amino acid motif DANGMDV. Also, a highly biased Vlambda2-14 use was evident in 72% of patients with a restricted light-chain CDR3, QVWDS(S/G)SDHPWV. Combined restricted heavy- and light-chain CDR3s were found in patients from all included countries. Although VH3-21+ CLLs have a remarkably predominant lambda expression, analyses of kappa deleting element indicated a conserved light-chain rearrangement order. The overall survival was poor in the VH3-21+ cohort (median survival, 88 months), with no significant difference in relation to mutation status or CDR3 homology. High ZAP-70 and CD38 expression was found in both mutated and unmutated VH3-21+ cases as well as a slight increase of 11q-aberrations. In summary, highly restricted B-cell receptors and worse outcome characterize VH3-21+ CLLs independent of geographic origin and mutation status.