Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.     

The value of laparoscopic cholecystectomy in the treatment of gallbladder pathologies]

We have prospectively studied all cholecystectomies performed in one year in our clinic in two groups: 190 cases performed laparoscopically and 98 open. We used standardized records and the EPI 5 program on an IBM compatible computer. There were no significant differences between groups regarding weight, sex and proportion of cases with acute cholecystitis. There were however major differences regarding age, type of habitat, ASA score and association with acute pancreatitis, obstructive jaundice and angiocholitis. Conversion of laparoscopic cholecystectomy to open procedure was imposed in 17 cases (not included in statistical analysis) due to technical difficulties (12 cases), haemorrhagic accidents (6 cases), injury of the common bile duct (1 case), stones lost in the abdominal cavity (3 cases), local peritonitis (5 cases). Laparoscopic cholecystectomy lasted a mean of 74 minutes. We encountered 3 specific complications: one CBD injury recognized intraoperatively and managed by Kehr's procedure (one CBD injury in the open cholecystectomy group), one small bowel perforation and one of biloma. Mortality averaged 0.5% in the LC group (one case of late postoperative stroke considered not related to the procedure) and 1% in the open cholecystectomy group. The hospital admission period was significantly reduced in the LC group (5 days vs. 12 days). LC appears as a safe procedure with a low complication rate. Conversion to open procedure is not a complication. Our study recommend LC as the method of choice in the treatment of gallbladder lithiasis.     

Assembly of a 1-Mb restriction-mapped cosmid contig spanning the candidate region for Finnish congenital nephrosis (NPHS1) in 19q13.1

We describe the assembly of a 1-Mb cosmid contig and restriction map spanning the candidate region for Finnish congenital nephrosis (NPHS1) in 19q13.1. The map was constructed from 16 smaller contigs assembled by fingerprinting, a BAC and a PAC clone, and 42 previously unmapped cosmids. In most cases, single-step cosmid walks were sufficient to join two previously assembled contigs, and all but one gap was filled from this cosmid contig library. The remaining gap of about 19 kb was spanned with a single BAC and a single PAC clone. EcoRI mapping of a dense set of overlapping clones validated the assembly of the map and indicated a length of 1040 kb for the contig. This high-resolution clone map provides an ideal resource for gene identification through cDNA selection, exon trapping, and DNA sequencing.     

Intrinsic limits of the efficiency of erbium 3-/spl mu/m lasers

Mathematical modeling, based on rate equations, is used to estimate the theoretical limit of the emission efficiency of 3-/spl mu/m Er:YAG laser (laser transition /sup 4/I/sub 11/2//spl rarr//sup 4/I/sub 13/2/) in both continuous wave (CW) and free-generation regimes. This model exclusively uses spectroscopic data and includes upconversion from both initial and terminal laser levels as well as the cross relaxation from the "pump level" /sup 4/S/sub 3/2/. The recirculation of the excitation on the metastable levels of the Er/sup 3+/ ion - produced by the energy-transfer processes, very active at high erbium concentrations - leads to supraunitary quantum efficiency and high emission efficiency in the CW regime. In the Q-switch regime, in contrast with CW (or free generation) regime, the energy-transfer processes are "frozen" during the giant pulse generation, the access to the stored energy is limited and the laser efficiency is rather low. In this paper, we find simple analytic expressions for the emission efficiency in CW, free-generation, and Q-switch regimes. The same figures of merit are used for all these regimes. The predictions of our model are then compared with available experimental results. Some suggestions to improve the overall efficiency of the 3-/spl mu/m erbium lasers, working in the Q-switch regime, are given.     

Alginit – ein effektives Adsorbens für die Entfernung endokrin wirksamer Substanzen aus Wässern

The detected concentrations and the variety of endocrine disrupting chemicals (EDC) in surface waters increase from year to year. The toxicity for various environmental organisms is a long known fact. Current methods for the removal of EDC, such as ozonation or activated carbon adsorption are associated with high costs. The naturally occurring rock alginite can complement the existing methods effectively. Its heterogeneous structure allows for removing polar and nonpolar EDC from water. Elimination rates up to 100 % were achieved.     

Drastic Attenuation of Pseudomonas aeruginosa Pathogenicity in a Holoxenic Mouse Experimental Model Induced by Subinhibitory Concentrations of Phenyllactic acid (PLA)

The discovery of communication systems regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. In this paper we describe the effect of subinhibitory concentrations of phenyllactic acid (PLA) on the pathogenicity of Pseudomonas aeruginosa in mice. The animals were inoculated by oral (p.o.), intranasal (i.n.), intravenous (i.v.) and intraperitoneal (i.p.) routes with P. aeruginoasa wild and PLA-treated cultures. The mice were followed up during 16 days after infection and the body weight, mortality and morbidity rate were measured every day. The microbial charge was studied by viable cell counts in lungs, spleen, intestinal mucosa and blood. The mice batches infected with wild P. aeruginosa bacterial cultures exhibited high mortality rates (100 % after i.v. and i.p. route) and very high cell counts in blood, lungs, intestine and spleen. In contrast, the animal batches infected with PLA treated bacterial cultures exhibited good survival rates (0 % mortality) and the viable cell counts in the internal organs revealed with one exception the complete abolition of the invasive capacity of the tested strains. In this study, using a mouse infection model we show that D-3-phenyllactic acid (PLA) can act as a potent antagonist of Pseudomonas (P.) aeruginosa pathogenicity, without interfering with the bacterial growth, as demonstrated by the improvement of the survival rates as well as the clearance of bacterial strains from the body.     

Expected utility operators and possibilistic risk aversion

In this paper expected utility operators are introduced as an abstractization of some notions of possibilistic expected utility, already existing in the literature. A general theory of possibilistic risk aversion which encompasses the already existing treatments is developed. The possibilistic risk premium associated with a fuzzy number, a utility function, an expected utility operator and a weighting function is defined. An approximate calculation formula of possibilistic risk premium expressed in terms of Arrow–Pratt index and a possibilistic variance associated with an expected utility operator is obtained. In an abstract context a Pratt-type theorem is proved.