Vascular complications after liver transplantation: A 5-year experience

During the past 5 years, 104 angiographic studies were performed in 87 patients (45 children and 42 adults) with 92 transplanted livers for evaluation of possible vascular complications. Seventy percent of the studies were abnormal. Hepatic artery thrombosis was the most common complication (seen in 42% of children studied, compared with only 12% of adults) and was a major complication that frequently resulted in graft failure, usually necessitating retransplantation. In six children, reconstitution of the intrahepatic arteries by collaterals was seen. Three survived without retransplant. Arterial stenosis at the anastomosis or in the donor hepatic artery was observed in 11% of patients. Portal vein thrombosis or stenosis occurred in 13% of patients. Two children and one adult with portal vein thrombosis demonstrated hepatopetal collaterals that reconstituted the intrahepatic portal vessels. Uncommon complications included anastomotic and donor hepatic artery pseudoaneurysms, a hepatic artery-dissecting aneurysm, pancreaticoduodenal mycotic aneurysms, hepatic artery-portal vein fistula, biliary-portal vein fistula, hepatic vein occlusion, and inferior vena cava thrombosis

Horizontal partial laryngectomy for supraglottic squamous cell carcinoma

Between 1981-1999, 75 patients treated for supraglottic SCC with horizontal supraglottic laryngectomy (HSL) at the Otolaryngology Head and Neck Surgery Department of Lausanne University Hospital were retrospectively studied. There were 16 patients with T1, 46 with T2 and 13 with T3 tumors. Among these, 16 patients (21%) had clinical neck disease corresponding to stage I, II, III and IV in 12, 39, 18 and 6 patients, respectively. All patients had HSL. Most patients had either elective or therapeutic bilateral level II-IV selective neck dissection. Six patients (8%) with advanced neck disease had ipsilateral radical and controlateral elective II-IV selective neck dissections. Adjuvant radiotherapy was given to 25 patients (30%) for either positive surgical margins (n=8), pathological nodal status (n=14) or both (n=3). Median follow-up was 48months (range, 24-199). Five-year disease-specific survival and locoregional and local control were 92, 90 and 92.5%, respectively. Among five patients who were diagnosed with local recurrence, one had a total laryngectomy (1.4%); the others were treated by endoscopic laser surgery. Two patients had both a local and regional recurrence. They were salvaged with combined surgery and radiotherapy, but eventually died of their disease. Cartilage infiltration seems to influence both local control (P=0.03) and disease-specific survival (P=0.06). There was a trend for worse survival with pathological node involvement (P=0.15) and extralaryngeal extension of the cancer (P=0.1). All patients except one recovered a close to normal function after the treatment. Aspiration was present in 16 patients (26%) in the early postoperative period. A median of 16days (7-9) was necessary to recover a close to normal diet. Decannulation took a median of 17days (8-93). Seven patients kept a tracheotomy tube for up to 3months because of persistent aspiration. There was no permanent tracheostomy or total laryngectomy for functional purposes. Horizontal supraglottic laryngectomy remains an adequate therapeutic alternative for supraglottic squamous cell carcinoma, offering an excellent oncological outcome. The postoperative functional morbidity is substantial, indicating the need for careful patient selection, but good laryngeal function recovery is the rule. The surgical alternative is endoscopic laser surgery, which may offer comparable oncological results with less functional morbidity. Nevertheless, these two different techniques need to be compared prospectivel

A Computational Comparison of Optimization Methods for the Golomb Ruler Problem

The Golomb ruler problem is defined as follows: Given a positive integer n, locate n marks on a ruler such that the distance between any two distinct pair of marks are different from each other and the total length of the ruler is minimized. The Golomb ruler problem has applications in information theory, astronomy and communications, and it can be seen as a challenge for combinatorial optimization algorithms. Although constructing high quality rulers is well-studied, proving optimality is a far more challenging task. In this paper, we provide a computational comparison of different optimization paradigms, each using a different model (linear integer, constraint programming and quadratic integer) to certify that a given Golomb ruler is optimal. We propose several enhancements to improve the computational performance of each method by exploring bound tightening, valid inequalities, cutting planes and branching strategies. We conclude that a certain quadratic integer programming model solved through a Benders decomposition and strengthened by two types of valid inequalities performs the best in terms of solution time for small-sized Golomb ruler problem instances. On the other hand, a constraint programming model improved by range reduction and a particular branching strategy could have more potential to solve larger size instances due to its promising parallelization features

Antagonism of the proinflammatory and pronociceptive actions of canonical and biased agonists of protease-activated receptor-2

Diverse proteases cleave protease-activated receptor-2 (PAR2) on primary sensory neurons and epithelial cells to evoke pain and inflammation. Trypsin and tryptase activate PAR2 by a canonical mechanism that entails cleavage within the extracellular N-terminus revealing a tethered ligand that activates the cleaved receptor. Cathepsin-S and elastase are biased agonists that cleave PAR2 at different sites to activate distinct signalling pathways. Although PAR2 is a therapeutic target for inflammatory and painful diseases, the divergent mechanisms of proteolytic activation complicate the development of therapeutically useful antagonists

Optimality Clue for Graph Coloring Problem

In this paper, we present a new approach which qualifies or not a solution found by a heuristic as a potential optimal solution. Our approach is based on the following observation: for a minimization problem, the number of admissible solutions decreases with the value of the objective function. For the Graph Coloring Problem (GCP), we confirm this observation and present a new way to prove optimality. This proof is based on the counting of the number of different k-colorings and the number of independent sets of a given graph G. Exact solutions counting problems are difficult problems (\#P-complete). However, we show that, using only randomized heuristics, it is possible to define an estimation of the upper bound of the number of k-colorings. This estimate has been calibrated on a large benchmark of graph instances for which the exact number of optimal k-colorings is known. Our approach, called optimality clue, build a sample of k-colorings of a given graph by running many times one randomized heuristic on the same graph instance. We use the evolutionary algorithm HEAD [Moalic et Gondran, 2018], which is one of the most efficient heuristic for GCP. Optimality clue matches with the standard definition of optimality on a wide number of instances of DIMACS and RBCII benchmarks where the optimality is known. Then, we show the clue of optimality for another set of graph instances. Optimality Metaheuristics Near-optimal

A novel class of heat and secretion stress-responsive genes is controlled by the autoregulated CssRS two-component system of Bacillus subtilis

Bacteria need dedicated systems that allow appropriate adaptation to the perpetual changes in their environments. In Bacillus subtilis, two HtrA-like proteases, HtrA and HtrB, play critical roles in the cellular response to secretion and heat stresses. Transcription of these genes is induced by the high-level production of a secreted protein or by a temperature upshift. The CssR-CssS two-component regulatory system plays an essential role in this transcriptional activation. Transcription of the cssRS operon is autoregulated and can be induced by secretion stress, by the absence of either HtrA or HtrB, and by heat stress in a HtrA null mutant strain. Two start sites are used for cssRS transcription, only one of which is responsive to heat and secretion stress. The divergently transcribed htrB and cssRS genes share a regulatory region through which their secretion and heat stress-induced expression is linked. This study shows that CssRS-regulated genes represent a novel class of heat-inducible genes, which is referred to as class V and currently includes two genes: htrA and htrB

High-salinity growth conditions promote tat-independent secretion of tat substrates in Bacillus subtilis

The Gram-positive bacterium Bacillus subtilis contains two Tat translocases, which can facilitate transport of folded proteins across the plasma membrane. Previous research has shown that Tat-dependent protein secretion in B. subtilis is a highly selective process and that heterologous proteins, such as the green fluorescent protein (GFP), are poor Tat substrates in this organism. Nevertheless, when expressed in Escherichia coli, both B. subtilis Tat translocases facilitated exclusively Tat-dependent export of folded GFP when the twin-arginine (RR) signal peptides of the E. coli AmiA, DmsA, or MdoD proteins were attached. Therefore, the present studies were aimed at determining whether the same RR signal peptide-GFP precursors would also be exported Tat dependently in B. subtilis. In addition, we investigated the secretion of GFP fused to the full-length YwbN protein, a strict Tat substrate in B. subtilis. Several investigated GFP fusion proteins were indeed secreted in B. subtilis, but this secretion was shown to be completely Tat independent. At high-salinity growth conditions, the Tat-independent secretion of GFP as directed by the RR signal peptides from the E. coli AmiA, DmsA, or MdoD proteins was significantly enhanced, and this effect was strongest in strains lacking the TatAy-TatCy translocase. This implies that high environmental salinity has a negative influence on the avoidance of Tat-independent secretion of AmiA-GFP, DmsA-GFP, and MdoD-GFP. We conclude that as-yet-unidentified control mechanisms reject the investigated GFP fusion proteins for translocation by the B. subtilis Tat machinery and, at the same time, set limits to their Tat-independent secretion, presumably via the Sec pathway

Efficient propagation of systematic uncertainties from calibration to analysis with the SnowStorm method in IceCube

Efficient treatment of systematic uncertainties that depend on a large number of nuisance parameters is a persistent difficulty in particle physics and astrophysics experiments. Where low-level effects are not amenable to simple parameterization or re-weighting, analyses often rely on discrete simulation sets to quantify the effects of nuisance parameters on key analysis observables. Such methods may become computationally untenable for analyses requiring high statistics Monte Carlo with a large number of nuisance degrees of freedom, especially in cases where these degrees of freedom parameterize the shape of a continuous distribution. In this paper we present a method for treating systematic uncertainties in a computationally efficient and comprehensive manner using a single simulation set with multiple and continuously varied nuisance parameters. This method is demonstrated for the case of the depth-dependent effective dust distribution within the IceCube Neutrino Telescope

Time-Integrated Neutrino Source Searches with 10 Years of IceCube Data.

This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1  TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector