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Concept: Insertion

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PURPOSE: The long-term success rate of dilation and/or internal urethrotomy is low in cases of recurrent urethral stricture disease. This study investigated the Memokath™044TW stent’s ability to maintain urethral patency after dilation or internal urethrotomy of recurrent urethral stricture. MATERIALS AND METHODS: Ninety-two patients with recurrent bulbar urethral strictures (mean length 2.7 cm) were treated with dilation or internal urethrotomy and randomized to short-term urethral catheter diversion (N=29) or insertion of a Memokath™044 stent (N=63). The primary endpoint was urethral patency as assessed by the passage of a calibrated endoscope. Secondary endpoints included urinary symptoms and uroflowmetry parameters. Stents were scheduled to remain in situ 12 months. RESULTS: The rate of successful stent insertion was 93.6% (59/63). The stented patients maintained patency significantly longer than controls (292 days vs. 84 days (median), p<0.001). The patency was reflected in significantly improved uroflowmetry and symptom scores. The stent was removed in 100% of patients. The most frequently noted side-effects in the stented patients were bacteriuria, hematuria, and penile pain - all usually mild and transient. There were no differences in sexual function between the Memokath and control patients. Stent dislocation and occlusion were observed in eight and three patients, respectively. CONCLUSIONS: Patients with recurrent bulbar urethral strictures treated with dilation or urethrotomy and a Memokath™044 stent maintained urethral patency significantly longer than those treated with dilation or urethrotomy alone. The stent's side-effect profile was favorable. The stent was straightforward to insert and was removed without difficulty - even after long-term placement.

Concepts: Time, Medical terms, Urethra, Stent, Restenosis, Urethral stricture, Urethrotomy, Insertion

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MOTIVATION: Next-generation sequencing techniques have facilitated a large-scale analysis of human genetic variation. Despite the advances in sequencing speed, the computational discovery of structural variants is not yet standard. It is likely that many variants have remained undiscovered in most sequenced individuals. RESULTS: Here, we present a novel internal segment size based approach, which organizes all, including concordant, reads into a read alignment graph, where max-cliques represent maximal contradiction-free groups of alignments. A novel algorithm then enumerates all max-cliques and statistically evaluates them for their potential to reflect insertions or deletions. For the first time in the literature, we compare a large range of state-of-the-art approaches using simulated Illumina reads from a fully annotated genome and present relevant performance statistics. We achieve superior performance, in particular, for deletions or insertions (indels) of length 20-100 nt. This has been previously identified as a remaining major challenge in structural variation discovery, in particular, for insert size based approaches. In this size range, we even outperform split-read aligners. We achieve competitive results also on biological data, where our method is the only one to make a substantial amount of correct predictions, which, additionally, are disjoint from those by split-read aligners. AVAILABILITY: CLEVER is open source (GPL) and available from http://clever-sv.googlecode.com. CONTACT: as@cwi.nl or tm@cwi.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Concepts: DNA, Genetics, Molecular biology, Human genome, Biotechnology, Data, Population genetics, Insertion

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♦ Background: There are no large studies that have examined ultra-short break-in period with a blind, bedside, midline approach to Tenckhoff catheter insertion.♦ Methods: Observational cohort study of 245 consecutive adult patients who underwent percutaneous catheter insertion for chronic peritoneal dialysis (PD) at our center from January 2009 to December 2013. There were 132 (53.9%) diabetics and 113 (46.1%) non-diabetics in the cohort.♦ Results: The mean break-in period for the percutaneous group was 2.68 ± 2.6 days. There were significantly more males among the diabetics (103 [78%] vs 66 [58.4%], p = 0.001). Diabetics had a significantly higher body mass index (BMI) (23.9 ± 3.7 kg/m(2)vs 22.2 ± 4 kg/m(2), p < 0.001) and lower serum albumin (33.1± 6.3 g/L vs 37 ± 6 g/L, p < 0.001) compared with non- diabetics. Poor catheter outflow was present in 6 (4.5%) diabetics and 16 (14.2%) non-diabetics (p= 0.009). Catheter migration was also significantly more common in the non-diabetic group (11 [9.7%] vs 2 [1.5%], p = 0.004). Primary catheter non-function was present in 17(15%) of the non-diabetics and in 7(5.3%) of the diabetics (p = 0.01). There were no mortality or major non-procedural complications during the catheter insertions. Among patients with 1 year of follow-up data, catheter survival (93/102 [91.2%] vs 71/82 [86.6%], p = 0.32) and technique survival (93/102 [91.2%] vs 70/82 [85.4%], p = 0.22) at 1 year was comparable between diabetics and non-diabetics, respectively.♦ Conclusions: Percutaneous catheter insertion by practicing nephrologists provides a short break-in period with very low mechanical and infective complications. Non-diabetic status emerged as a significant risk factor for primary catheter non-function presumed to be due to more patients with lower BMI and thus smaller abdominal cavities. This is the first report that systematically compares diabetic and non-diabetic patients.

Concepts: Cohort study, Nephrology, Dialysis, Obesity, Body mass index, Peritoneum, Insertion, Insertion sort

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Background Three anatomical sites are commonly used to insert central venous catheters, but insertion at each site has the potential for major complications. Methods In this multicenter trial, we randomly assigned nontunneled central venous catheterization in patients in the adult intensive care unit (ICU) to the subclavian, jugular, or femoral vein (in a 1:1:1 ratio if all three insertion sites were suitable [three-choice scheme] and in a 1:1 ratio if two sites were suitable [two-choice scheme]). The primary outcome measure was a composite of catheter-related bloodstream infection and symptomatic deep-vein thrombosis. Results A total of 3471 catheters were inserted in 3027 patients. In the three-choice comparison, there were 8, 20, and 22 primary outcome events in the subclavian, jugular, and femoral groups, respectively (1.5, 3.6, and 4.6 per 1000 catheter-days; P=0.02). In pairwise comparisons, the risk of the primary outcome was significantly higher in the femoral group than in the subclavian group (hazard ratio, 3.5; 95% confidence interval [CI], 1.5 to 7.8; P=0.003) and in the jugular group than in the subclavian group (hazard ratio, 2.1; 95% CI, 1.0 to 4.3; P=0.04), whereas the risk in the femoral group was similar to that in the jugular group (hazard ratio, 1.3; 95% CI, 0.8 to 2.1; P=0.30). In the three-choice comparison, pneumothorax requiring chest-tube insertion occurred in association with 13 (1.5%) of the subclavian-vein insertions and 4 (0.5%) of the jugular-vein insertions. Conclusions In this trial, subclavian-vein catheterization was associated with a lower risk of bloodstream infection and symptomatic thrombosis and a higher risk of pneumothorax than jugular-vein or femoral-vein catheterization. (Funded by the Hospital Program for Clinical Research, French Ministry of Health; ClinicalTrials.gov number, NCT01479153 .).

Concepts: Clinical trial, Blood, Vein, Central venous catheter, Catheter, Deep vein thrombosis, Deep vein, Insertion

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High-throughput sequencing of transposon (Tn) libraries created within entire genomes identifies and quantifies the contribution of individual genes and operons to the fitness of organisms in different environments. We used insertion-sequencing (INSeq) to analyze the contribution to fitness of all non-essential genes in the chromosome of Pseudomonas aeruginosa strain PA14 based on a library of ∼300,000 individual Tn insertions. In vitro growth in LB provided a baseline for comparison with the survival of the Tn insertion strains following 6 days of colonization of the murine gastrointestinal tract as well as a comparison with Tn-inserts subsequently able to systemically disseminate to the spleen following induction of neutropenia. Sequencing was performed following DNA extraction from the recovered bacteria, digestion with the MmeI restriction enzyme that hydrolyzes DNA 16 bp away from the end of the Tn insert, and fractionation into oligonucleotides of 1,200-1,500 bp that were prepared for high-throughput sequencing. Changes in frequency of Tn inserts into the P. aeruginosa genome were used to quantify in vivo fitness resulting from loss of a gene. 636 genes had <10 sequencing reads in LB, thus defined as unable to grow in this medium. During in vivo infection there were major losses of strains with Tn inserts in almost all known virulence factors, as well as respiration, energy utilization, ion pumps, nutritional genes and prophages. Many new candidates for virulence factors were also identified. There were consistent changes in the recovery of Tn inserts in genes within most operons and Tn insertions into some genes enhanced in vivo fitness. Strikingly, 90% of the non-essential genes were required for in vivo survival following systemic dissemination during neutropenia. These experiments resulted in the identification of the P. aeruginosa strain PA14 genes necessary for optimal survival in the mucosal and systemic environments of a mammalian host.

Concepts: DNA, Gene, Bacteria, Evolution, Molecular biology, Genome, Pseudomonas aeruginosa, Insertion

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OBJECTIVES:: The vast majority of ICU patients require some form of venous access. There are no evidenced-based guidelines concerning the use of either central or peripheral venous catheters, despite very different complications. It remains unknown which to insert in ICU patients. We investigated the rate of catheter-related insertion or maintenance complications in two strategies: one favoring the central venous catheters and the other peripheral venous catheters. DESIGN:: Multicenter, controlled, parallel-group, open-label randomized trial. SETTING:: Three French ICUs. PATIENTS:: Adult ICU patients with equal central or peripheral venous access requirement. INTERVENTION:: Patients were randomized to receive central venous catheters or peripheral venous catheters as initial venous access. MEASUREMENTS AND RESULTS:: The primary endpoint was the rate of major catheter-related complications within 28 days. Secondary endpoints were the rate of minor catheter-related complications and a composite score-assessing staff utilization and time spent to manage catheter insertions. Analysis was intention to treat. We randomly assigned 135 patients to receive a central venous catheter and 128 patients to receive a peripheral venous catheter. Major catheter-related complications were greater in the peripheral venous catheter than in the central venous catheter group (133 vs 87, respectively, p = 0.02) although none of those was life threatening. Minor catheter-related complications were 201 with central venous catheters and 248 with peripheral venous catheters (p = 0.06). 46% (60/128) patients were managed throughout their ICU stay with peripheral venous catheters only. There were significantly more peripheral venous catheter-related complications per patient in patients managed solely with peripheral venous catheter than in patients that received peripheral venous catheter and at least one central venous catheter: 1.92 (121/63) versus 1.13 (226/200), p < 0.005. There was no difference in central venous catheter-related complications per patient between patients initially randomized to peripheral venous catheters but subsequently crossed-over to central venous catheter and patients randomized to the central venous catheter group. Kaplan-Meier estimates of survival probability did not differ between the two groups. CONCLUSION:: In ICU patients with equal central or peripheral venous access requirement, central venous catheters should preferably be inserted: a strategy associated with less major complications. (Crit Care Med 2013; 41:0-0).

Concepts: Epidemiology, Randomized controlled trial, Central venous catheter, Catheter, Catheters, Peripheral venous catheter, Insertion, Intention to treat analysis

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The pivotal step on the mitochondrial pathway to apoptosis is permeabilization of the mitochondrial outer membrane (MOM) by oligomers of the B-cell lymphoma-2 (Bcl-2) family members Bak or Bax. However, how they disrupt MOM integrity is unknown. A longstanding model is that activated Bak and Bax insert two α-helices, α5 and α6, as a hairpin across the MOM, but recent insights on the oligomer structures question this model. We have clarified how these helices contribute to MOM perforation by determining that, in the oligomers, Bak α5 (like Bax α5) remains part of the protein core and that a membrane-impermeable cysteine reagent can label cysteines placed at many positions in α5 and α6 of both Bak and Bax. The results are inconsistent with the hairpin insertion model but support an in-plane model in which α5 and α6 collapse onto the membrane and insert shallowly to drive formation of proteolipidic pores.

Concepts: DNA, Protein, Apoptosis, Oligomer, Caspase, Bcl-2, BH3 interacting domain death agonist, Insertion

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Use of a bougie is not without risk, and insertion too far may cause airway injury. We designed a new bougie with a ‘traffic light’ system to indicate depth of insertion. Forty anaesthetists were randomly assigned to insert either a conventional single-coloured bougie or a novel traffic light bougie. Depth of insertion was measured before and after railroading a tracheal tube. Participants were not informed as to the purpose of the colouring system. The median (IQR [range]) insertion depth of the traffic light bougie was 22 (21-24 [19-27]) cm and for the conventional bougie was 28 (21-32 [20-35]) cm (p = 0.011). Median (IQR [range]) insertion depth after railroading for the traffic light bougie was 25 (25-28 [21-34]) cm and for the conventional bougie was 30.5 (27-35 [23-40]) cm (p = 0.003). This simple colouring system appears to allow intuitive use and significantly reduced the depth of bougie insertion. This system could be also used with other airway exchange devices to improve safety.

Concepts: Interquartile range, Insertion

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INTRODUCTION: Intraosseous access is increasingly recognised as an effective alternative vascular access to peripheral venous access. We aimed to prospectively study the patients receiving prehospital intraosseous access with the EZ-IO®, and to compare our results with those of the available literature. METHODS: Every patient who required an intraosseous access with the EZ-IO from January 1(st), 2009 to December 31(st), 2011 was included. The main data collected were: age, sex, indication for intraosseous access, localisation of insertion, success rate, drugs and fluids administered, and complications. All published studies concerning the EZ-IO device were systematically searched and reviewed for comparison. RESULTS: Fifty-eight patients representing 60 EZ-IO procedures were included. Mean age was 47 years (range 0.5-91), and the success rate was 90%. The main indications were cardiorespiratory arrest (74%), major trauma (12%), and shock (5%). The anterior tibia was the main route. The main drugs administered were adrenaline (epinephrine), atropine and amiodarone. No complications were reported. We identified 30 heterogeneous studies representing 1603 EZ-IO insertions. The patients' characteristics and success rate were similar to our study. Complications were reported in 13 cases (1.3%). CONCLUSION: The EZ-IO provides an effective way to achieve vascular access in the pre-hospital setting. Our results were similar to the cumulative results of all studies involving the use of the EZ-IO, and that can be used for comparison for further studies.

Concepts: Cardiac arrest, Cardiopulmonary resuscitation, Epinephrine, Emergency medical services, Insertion, Insertion sort, Bubble sort, Selection sort

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To determine the effects of administration of 25 mg of PGF2α 7 d prior to the initiation of the 7-d CO-Synch + controlled internal drug release (CIDR) fixed-time AI (TAI) protocol, 985 Bos taurus beef heifers were enrolled in a completely randomized design at 9 locations from April to July of 2016. Within location, all heifers were randomly assigned to 1 of 2 treatments: 1) CONTROL (n = 496); 100 µg injection of GnRH and a CIDR insert for 7 d [day 7], administration of 25 mg of PGF2α at CIDR removal [day 0], followed by a second injection of GnRH and TAI 54 ± 2 h later; or 2) PRESYNCH (n = 489); same as CONTROL but heifers received an additional injection of 25 mg of PGF2α 7 d prior [day 14] to CIDR insertion. Estrous detection patches were applied to all heifers on day 14 and were evaluated for estrual activity on day 7. Similarly, estrus alert patches were placed on all heifers on day 0 and evaluated for estrual activity at the time of TAI. Pregnancy was diagnosed via transrectal ultrasonography between 35 and 55 d after TAI. The percentage of heifers exhibiting estrus between days 14 and 7 was greater (P < 0.001) for the PRESYNCH (70.1 ± 2.4%) than the CONTROL (41.1 ± 2.3%) treatment, whereas the percentage of heifers exhibiting estrus between day 0 and TAI was greater (P < 0.001) for the CONTROL (55.6 ± 2.4%) than the PRESYNCH (39.7 ± 2.5%) treatment. Estrus response rates differed (P < 0.001) among locations. Pregnancy rates to TAI differed (P = 0.023) among locations; however, they did not differ (P = 0.739) between CONTROL and PRESYNCH treatments (45.4 ± 2.5 vs. 43.2 ± 2.5%, respectively). Final breeding season pregnancy rates did not differ (P = 0.811) between treatments. Therefore, an injection of PGF2α 7 d prior to initiation of the 7-d CO-Synch + CIDR protocol failed to improve pregnancy rates to TAI in replacement beef heifers.

Concepts: Cattle, Medical ultrasonography, Randomness, Initiation, Transrectal ultrasonography, Control, Insertion, Bos