A calibrated diversity assay for nucleic acid libraries using DiStRO—a Diversity Standard of Random Oligonucleotides

We have determined diversities exceeding 1012 different sequences in an annealing and melting assay using synthetic randomized oligonucleotides as a standard. For such high diversities, the annealing kinetics differ from those observed for low diversities, favouring the remelting curve after annealing as the best indicator of complexity. Direct comparisons of nucleic acid pools obtained from an aptamer selection demonstrate that even highly complex populations can be evaluated by using DiStRO, without the need of complicated calculations

Sequence–structure relationships in RNA loops: establishing the basis for loop homology modeling

The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three-dimensional structures of RNA molecules. A comprehensive loop-structure data set was created and organized into distinct clusters based on structural and sequence similarity. We detected clear evidence of the hallmark of homology present in the sequence–structure relationships in loops. Loops differing by <25% in sequence identity fold into very similar structures. Thus, our results support the application of homology modeling for RNA loop model building. We established a threshold that may guide the sequence divergence-based selection of template structures for RNA loop homology modeling. Of all possible sequences that are, under the assumption of isosteric relationships, theoretically compatible with actual sequences observed in RNA structures, only a small fraction is contained in the Rfam database of RNA sequences and classes implying that the actual RNA loop space may consist of a limited number of unique loop structures and conserved sequences. The loop-structure data sets are made available via an online database, RLooM. RLooM also offers functionalities for the modeling of RNA loop structures in support of RNA engineering and design efforts

Significance of Dynamic Pore PressureVariations - Comparison of Observations on Mud Volcanoes on the Costa Rica Margin and in the Gulf of Cadiz

Research in the cooperative research center (SFB) 574 "Volatiles and Fluids in Subduction Zones" at the University Kiel focuses on volatile and fluid exchange processes at subduction zones. These have a significant impact on the long-term geochemical evolution of the hydrosphere and atmosphere. In the SFB 574 working area off Central America more than 120 mud volcanoes, mud diapirs and cold seeps have been identified and sampled. To better understand the internal dynamics of these structures and the temporal variability of fluid expulsion an in-situ tool for monitoring shallow pore pressure variations was devised. The tool (PWPL) monitors pore pressure variations along a 2m profile in the shallow subsurface using a stinger with 4 pressure ports. Positioned with a video-guided lander the stinger is gently pushed into the seafloor where it remains for several weeks or months in autonomous mode before being retrieved. While particular emphasis was placed on the convergent margin of Central America, mud volcanoes in other tectonic settings suitable for long-term observations of fluid flux are used for comparison. Here we will present data and interpretations from two mud volcanoes off Costa Rica and in the Gulf of Cadiz where we have conducted successful tests. Pore pressure data from short-term tests on Mound 11 on the continental slope off Costa Rica are compared with new results from a long-term (3-month) campaign on the Captain Arutjunov deep water mud volcano in the Gulf of Cadiz. Rates of fluid flow at both structures have been thoroughly characterized and quantified with geochemical methods providing a frame of reference for judging the significance of dynamic pore pressure variations

Medical Expulsive Therapy for Ureterolithiasis: The EAU Recommendations in 2016

Medical expulsive therapy (MET), in particular alpha-blockers, have been recommended as supportive medication if observational treatment of a ureteral stone was an option. Over the years, a considerable number of randomized controlled trials (RCT) as well as several meta-analyses have been published on MET, supporting the use of a-blockers. However, several recently published high quality, large, placebo-controlled randomized trials raised serious doubts about the effectiveness of alpha-blockers. The contradictory results of meta-analyses of small RCTs versus the findings of large, well conducted multicenter trials show the methodological vulnerability of meta-analyses, in particular if small single center, lower quality, papers have been included. Small single center trials, for instance, tend to show larger treatment effects compared to multicenter RCTs. It also shows the responsibility of careful planning when conducting a RCT. Trial registration as a prerequisite for approval by ethics committees could in addition minimize publication bias. Weighting the current evidence on whether to use MET, or not, it seems that in distal ureteral stones larger than 5 mm, there may be a potential therapeutic benefit for the use of alpha-blockers. Patients should be informed about the possible, but as yet unproven benefit of using alpha-blockers in this situation, as well as their off-label use and potential side effects. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved

Tract Sizes in Miniaturized Percutaneous Nephrolithotomy: A Systematic Review from the European Association of Urology Urolithiasis Guidelines Panel

Context: Miniaturized instruments for percutaneous nephrolithotomy (PNL), utilizing tracts sized &lt;= 22 Fr, have been developed in an effort to reduce the morbidity and increase the efficiency of stone removal compared with standard PNL (&gt; 22 Fr). Objective: We systematically reviewed all available evidence on the efficacy and safety of miniaturized PNL for removing renal calculi. Evidence acquisition: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Since it was not possible to perform a meta-analysis, the data were summarized in a narrative synthesis. Evidence synthesis: After screening 2945 abstracts, 18 studies were included (two randomized controlled trials [RCTs], six nonrandomized comparative studies, and 10 case series). Thirteen studies were full-text articles and five were only available as congress abstracts. The size of tracts used in miniaturized procedures ranged from 22 Fr to 4.8 Fr. The largest mean stone size treated using small instruments was 980 mm(2). Stone-free rates were comparable in miniaturized and standard PNL procedures. Procedures performed with small instruments tended to be associated with significantly lower blood loss, while the procedure duration tended to be significantly longer. Other complications were not notably different between PNL types. Study designs and populations were heterogeneous. Study limitations included selection and outcome reporting bias, as well as a lack of information on relevant confounding factors. Conclusions: The studies suggest that miniaturized PNL is at least as efficacious and safe as standard PNL for the removal of renal calculi. However, the quality of the evidence was poor, drawn mainly from small studies, the majority of which were single-arm case series, and only two of which were RCTs. Furthermore, the tract sizes used and types of stones treated were heterogeneous. Hence, the risks of bias and confounding were high, highlighting the need for more reliable data from RCTs. Patient summary: Removing kidney stones via percutaneous nephrolithotomy (PNL) using smaller sized instruments (mini-PNL) appears to be as effective and safe as using larger (traditional) instruments, but more clinical research is needed. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved

What are the Benefits and Harms of Ureteroscopy Compared with Shock-wave Lithotripsy in the Treatment of Upper Ureteral Stones? : A Systematic Review

Funding/Support and role of the sponsor: None.Peer reviewedPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprin

What are the Benefits and Harms of Ureteroscopy Compared with Shock-wave Lithotripsy in the Treatment of Upper Ureteral Stones? A Systematic Review

Context: Extracorporeal shock wave lithotripsy (SWL) and ureteroscopy (URS), with or without intracorporeal lithotripsy, are the most common treatments for upper ureteric stones. With advances in technology, it is unclear which treatment is most effective and/or safest. Objective: To systematically review literature reporting benefits and harms of SWL and URS in the management of upper ureteric stones. Evidence acquisition: Databases including Medline, Embase, and the Cochrane library were searched from January 2000 to November 2014. All randomised controlled trials (RCTs), quasi-randomised controlled trials, and nonrandomised studies comparing any subtype or variation of URS and SWL were included. The primary benefit outcome was stone-free rate (SFR). The primary harm outcome was complications. Secondary outcomes included retreatment rate, need for secondary, and/or adjunctive procedures. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the quality of evidence. Evidence synthesis: Five thousand-three hundred and eighty abstracts and 387 full-text articles were screened. Forty-seven studies met inclusion criteria; 19 (39.6%) were RCTs. No studies on children met inclusion criteria. URS and SWL were compared in 22 studies (4 RCTs, 1 quasi-randomised controlled trial, and 17 nonrandomised studies). Meta-analyses were inappropriate due to data heterogeneity. SFR favoured URS in 9/22 studies. Retreatment rates were higher for SWL compared with URS in all studies but one. Longer hospital stay and adjunctive procedures (most commonly the insertion of a JJ stent) were more common when primary treatment was URS. Complications were reported in 11 out of 22 studies. In eight studies, it was possible to report this as a Clavien-Dindo Grade. Higher complication rates across all grades were reported for URS compared with SWL. For intragroup (intra-SWL and intra-URS) comparative studies, 25 met the inclusion criteria. These studies varied greatly in outcomes measured with data being heterogeneous. Conclusions: Compared with SWL, URS was associated with a significantly greater SFR up to 4 wk but the difference was not significant at 3 mo in the included studies. URS was associated with fewer retreatments and need for secondary procedures, but with a higher need for adjunctive procedures, greater complication rates, and longer hospital stay. Patient summary: In this paper, the relative benefits and harms of the two most commonly offered treatment options for urinary stones located in the upper ureter were reviewed. We found that both treatments are safe and effective options that should be offered based on individual patient circumstances and preferences. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved