Added value of randomised biopsy to multiparametric magnetic resonance imaging‐targeted biopsy of the prostate in a contemporary cohort

Objective To assess the added value of concurrent systematic randomised ultrasonography-guided biopsy (SBx) to multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy and the additional rate of overdiagnosis of clinically insignificant prostate cancer (ciPCa) by SBx in a large contemporary, real-world cohort. Patients and Methods A total of 1552 patients with positive mpMRI and consecutive mpMRI-targeted biopsy and SBx were enrolled. Added value and the rate of overdiagnosis by SBx was evaluated. Primary outcome: added value of SBx, defined as detection rate of clinically significant PCa (csPCa; International Society of Urological Pathology [ISUP] Grade ≥2) by SBx, while mpMRI-targeted biopsy was negative or showed ciPCa (ISUP Grade 1). Secondary outcome: rate of overdiagnosis by SBx, defined as detection of ciPCa in patients with negative mpMRI-targeted biopsy and PSA level of <10 ng/mL. Results Detection rate of csPCa by mpMRI-targeted biopsy and/or SBx was 753/1552 (49%). Added value of SBx was 145/944 (15%). Rate of overdiagnosis by SBx was 146/656 (22%). Added value of SBx did not change when comparing patients with previous prostate biopsy and biopsy naïve patients. In multivariable analysis, a Prostate Imaging-Reporting and Data System (PI-RADS) 4 index lesion (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.66–6.78; P = 0.001), a PI-RADS 5 index lesion (OR 2.89, 95% CI 1.39–6.46; P = 0.006) and age (OR 1.05, 95% CI 1.03–1.08; P < 0.001) were independently associated with added value of SBx. Conclusions In our real-world analysis, we saw a significant impact on added value and added rate of overdiagnosis by SBx. Subgroup analysis showed no significant decrease of added value in any evaluated risk group. Therefore, we do not endorse omitting concurrent SBx to mpMRI-guided biopsy of the prostate

Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis

CCL17 is produced by conventional dendritic cells, signals through CCR4 on regulatory T (Treg) cells and drives atherosclerosis by suppressing Treg functions through yet undefined mechanisms. Here we show that conventional dendritic cells from CCL17-deficient mice display a pro-tolerogenic phenotype and transcriptome that is not phenocopied in mice lacking its cognate receptor CCR4. In the plasma of CCL17-deficient mice, CCL3 was the only decreased cytokine/chemokine. We found that CCL17 signaled through CCR8 as an alternate high-affinity receptor, which induced CCL3 expression and suppressed Treg functions in the absence of CCR4. Genetic ablation of CCL3 and CCR8 in CD4+ T cells reduced CCL3 secretion, boosted FoxP3+ Treg numbers and limited atherosclerosis. Conversely, CCL3 administration exacerbated atherosclerosis and restrained Treg differentiation. In symptomatic versus asymptomatic human carotid atheroma, CCL3 expression was increased, whereas FoxP3 expression was reduced. Together, we identified a non-canonical chemokine pathway whereby CCL17 interacts with CCR8 to yield a CCL3-dependent suppression of atheroprotective Treg cells. Doring, van der Vorst, Yan, Neideck et al. present a non-canonical chemokine pathway involving CCL17 signaling through CCR8, which induces CCL3 expression independent of CCR4 and suppresses the functions of atheroprotective Treg cells

Some remarks on interrelating environmental changes and ecological, socio-economic problems in the development of the early Egyptian inundation culture

The Egyptian inundation culture was a special kind of the so-called hydraulic cultures. Gradual cultural developments with socio-economic changes took place under the special conditions of repeated far-reaching and drastic environmental and ecological changes during late Pleistocene and early Holocene times, not only in the Nile valley. The development of the Egyptian and other early high civilizations was only possible after the development of agriculture providing a sufficient surplus in food. Agriculture and the production of (staple) food represented a new existence basis with effects on the accumulation of goods and the extension and intensification of economic and social inequality, therewith opening the possibility of new socio-economic relationships. But the development of the early high civilizations cannot be explained solely through the intensification of the agricultural component within a complex economy, other factors must have entered into play. The necessity of a permanent, supervised, intensive cooperation among a representative number of members within a society in great socially relevant enterprises formed one decisive criterium for the development of early high civilizations, not only in Egypt.La culture égyptienne de l'inondation constitue un type spécial de ce qu'on appelle les cultures hydrauliques. Des changements écologiques et environnementaux de grande portée - voire radicaux - dus à certaines conditions spécifiques et répétées, menèrent vers la fin du Pleistocène et le début de l'Holocène à des développements culturels qui, peu à peu, aboutirent aussi à des changements socio-économiques. Ce fait n'est pas exclusif à la vallée du Nil. Le développement de la civilisation égyptienne et d'autres grandes cultures n'est devenu possible qu'après l'existence d'une composante agricole permettant une production suffisante de denrées alimentaires. Ainsi l'économie rurale et la production de denrées alimentaires formèrent une nouvelle base d’existence avec la conséquence logique d'une accumulation des biens, et, par là, une extension et une intensification de l'inégalité économique et sociale. Ce fait a rendu possible la formation de nouvelles relations socio-économiques. Mais la formation des premières hautes cultures ne s'explique pas seulement par une intensification de la composante agricole à l'intérieur d'économies complexes ; d'autres facteurs doivent avoir eu leur influence. La nécessité d'une coopération permanente, guidée et intensive, d'un nombre représentatif de membres d'une société à de grandes entreprises constitue un des critères décisifs pour la formation des premières grandes civilisations, pas seulement dans la vallée du Nil.Atzler Michael. Some remarks on interrelating environmental changes and ecological, socio-economic problems in the development of the early Egyptian inundation culture. In: Archéo-Nil. Revue de la société pour l'étude des cultures prépharaoniques de la vallée du Nil, n°5, 1995. L'eau et le pouvoir. pp. 7-65

MECHANICAL CHARACTERISATION OF IN-SITU BONDING BETWEEN PEEK FILAMENTS AND LAMINATES IN THE FFF PROCESS

Fused filament fabrication (FFF) of high-temperature, aerospace-grade thermoplastics like PEEK has made significant progress in recent years and has become an established process for 3D-printing of complex parts. However, possibilities of adding long or continuous fibres are still limited and the introduced thermal stresses limit the maximum part dimensions. To overcome these limitations, this work investigates the potential of bonding FFF printed parts in-situ onto continuous fibre reinforced laminates. This process allows the combination of the complexity of 3D-printing with large scale manufacturing processes for high-performance structures. The investigation is divided in two steps. Firstly, the effect of process temperatures on the inter-layer bonding of printed PEEK is investigated. On this basis, the optimal process parameters for the bonding of printed PEEK onto PEEK laminates are analysed. The results show a strong correlation between the process temperatures and the inter-layer bonding as well as the bonding between filament and laminates. The process influences shown form the basis for future hybrid component and process designs

Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis

Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated as lipid particles accumulate and become trapped in vessel walls. The subsequent immune response, involving both adaptive and immune cells, progresses plaque development, which may be exacerbated under dyslipidemic conditions. Broad evidence, especially from animal models, clearly demonstrates the effect of lipids on immune cells from their development in the bone marrow to their phenotypic switching in circulation. Interestingly, recent research has also shown a long-lasting epigenetic signature from lipids on immune cells. Traditionally, cardiovascular therapies have approached atherosclerosis through lipid-lowering medications because, until recently, anti-inflammatory therapies have been largely unsuccessful in clinical trials. However, the recent Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) provided pivotal support of the inflammatory hypothesis of atherosclerosis in man spurring on anti-inflammatory strategies to treat atherosclerosis. In this review, we describe the interactions between lipids and immune cells along with their specific outcomes as well as discuss their future perspective as potential cardiovascular targets