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The objective of this study was to identify sources and linkages among methicillin-resistant Staphylococcus aureus infections using whole-genome sequencing (WGS).A total of 56 samples were obtained from all patients with a confirmed MRSA infection over 6 months at University of Florida-Health Jacksonville. Samples were cultured and sequenced; data was analyzed on an automated cloud-based platform. Genetic Clusters were defined as40 single nucleotide polymorphisms. Temporal Clusters were defined as ≥5 MRSA cases over 3 days.We found 7 Genetic Clusters comprising 15 samples. Four Genetic Clusters contained patients with non-overlapping stays (3-10 weeks apart), 3 of which contained patients who shared the same Unit. We also found 5 Temporal Clusters comprising 23 samples, although none of the samples were genetically related.Results showed that temporal clustering may be a poor indicator of genetic linkage. Shared epidemiological characteristics between patients in Genetic Clusters may point toward previously unidentified hospital sources. Repeated observation of related strains is also consistent with ongoing MRSA transmission within the surrounding high-risk community.WGS is a valuable tool for hospital infection prevention and control.

We report on the first γ-ray spectroscopy of 51,53K produced via the 52,54Ca(p,2p) reactions at ∼250 MeV/nucleon. Unambiguous final-state angular-momentum assignments were achieved for beam intensities down to few particles per second by using a new technique based on reaction vertex tracking combined with a thick liquid-hydrogen target. Through γ-ray spectroscopy and exclusive parallel momentum distribution analysis, 3/2+ ground states and 1/2+ first excited states in 51,53K were established quantifying the natural ordering of the 1 d 3 / 2 and 2 s 1 / 2 proton-hole states that are restored at N = 32 and 34. State-of-the-art ab initio calculations and shell-model calculations with improved phenomenological effective interactions reproduce the present data and predict consistently the increase of the E(1/2 1 + ) - E(3/2 1 + ) energy differences towards N = 40.

The Spallation Neutron Source (SNS) was designed and constructed by a collaboration of six U.S. Department of Energy national laboratories. The SNS accelerator system consists of a 1 GeV linear accelerator and an accumulator ring providing 1.4 MW of proton beam power in microsecond-long beam pulses to a liquid mercury target for neutron production. The accelerator complex consists of a front-end negative hydrogen-ion injector system, an 87 MeV drift tube linear accelerator, a 186 MeV side-coupled linear accelerator, a 1 GeV superconducting linear accelerator, a 248-m circumference accumulator ring and associated beam transport lines. The accelerator complex is supported by ~100 high-power RF power systems, a 2 K cryogenic plant, ~400 DC and pulsed power supply systems, ~400 beam diagnostic devices and a distributed control system handling ~100,000 I/O signals. The beam dynamics design of the SNS accelerator is presented, as is the engineering design of the major accelerator subsystems.

We demonstrate concentration-dependent Forster-type energy transfer in a luminescent solar concentrator (LSC) material containing two high quantum yield laser dyes in a PMMA matrix. FRET heterotransfer is shown to be approximately 50% efficient in the regime of 2×10 −3 molal acceptor dye by weight in the host polymer. The two dyes used have been well studied for solar concentrator applications: BASF's Lumogen Red 305, and Exciton Chemical Company's DCM both demonstrate desirable stability, quantum yield, and complementary absorption spectra. We demonstrate how multiple-dye LSC devices employing FRET increase the absorption of air mass 1.5 solar irradiance without affecting the self-absorption properties of the film. Color tunability may be achieved through the addition of additional absorbers while minimizing the impact on waveguide efficiency.

We characterize the infinite upper triangular matrices (which we call formal proximity matrices) that can arise as proximity matrices associated with zero-dimensional valuations dominating regular noetherian local rings. In particular, for every regular noetherian local ring R of the appropriate dimension, we give a sufficient condition for such a formal proximity matrix to be the proximity matrix associated with a real rank one valuation dominating R. Furthermore, we prove that in the special case of rational function fields, each formal proximity matrix arises as the proximity matrix of a valuation whose value group is computable from the formal proximity matrix. We also give an example to show that this is false for more general fields. Finally in the case of characteristic zero, our constructions can be seen as a particular case of a structure theorem for zero-dimensional valuations dominating equicharacteristic regular noetherian local rings.

We study zero-dimensional valuations dominating a regular local ring of dimension n ≥ 2 . For this we introduce the proximity matrix and the multiplicity sequence (extending classical definitions of the case n = 2 ) that are associated with the sequence of the successive quadratic transforms of the ring along the valuation. We describe the precise relations between these invariants and study their properties.

Background Asthma functional genomics studies are challenging because it is difficult to relate gene expression changes to specific disease mechanisms or pathophysiologic features. Use of simplified model systems might help to address this problem. One such model is the IL-13/Epi (IL-13–overexpressing transgenic mice with STAT6 expression limited to epithelial cells) focused transgenic mouse, which isolates the effects of a single mediator, IL-13, on a single cell type, the airway epithelial cell. These mice develop airway hyperreactivity and mucus overproduction but not airway inflammation. Objective To identify how effects of IL-13 on airway epithelial cells contribute to gene expression changes in murine asthma models and determine whether similar changes are seen in people with asthma. Methods We analyzed gene expression in ovalbumin allergic mice, IL-13–overexpressing mice, and IL-13/Epi mice with microarrays. We analyzed the expression of human orthologues of genes identified in the mouse studies in airway epithelial cells from subjects with asthma and control subjects. Results In comparison with the other 2 models, IL-13/Epi mice had a remarkably small subset of gene expression changes. Human orthologues of some genes identified as increased in the mouse models were more highly expressed in airway epithelial cells from subjects with asthma than in controls. These included calcium-activated chloride channel 1, 15-lipoxygenase, trefoil factor 2, and intelectin. Conclusion The combination of focused transgenic models, DNA microarray analyses, and translational studies provides a powerful approach for analyzing the contributions of specific mediators and cell types and for focusing attention on a limited number of genes associated with specific pathophysiologic aspects of asthma.

Some ultrastructural changes can be observed in diseased Saccharum officinarum L. (cv. Cuba 120-78) plants with visual symptoms of yellow leaf syndrome (YLS), used to discriminate between healthy and diseased plants. Abaxial epidermis of diseased leaves shows a large amount of adhered superficial bodies, which partially occluded some stomata. Bundle sheath cells surrounding the bottom of phloem of diseased leaves are separated from the conducting tissues by a large layer of an amorphous matrix similar to wax. Debris of the end wall can be observed in large xylem vessels. Sometimes, spherical bodies similar to phytoplasma can be observed in the intercellular spaces of bundle sheath cells. These particles have never been observed in healthy plants. YLS was also associated to an increase of the concentration of reducing sugars, glucose index, and glycoproteins recovered in juices whereas the amount of sucrose decreases. Sugarcane juices obtained from both healthy and YLS-affected Cuba 120-78 cultivars of sugarcane contained putrescine (PUT), cadaverine (CAD), spermidine and spermine (SPM) as free and macromolecules-conjugated compounds. Only CAD and SPM appeared as acid-soluble conjugates to small molecules whereas PUT and CAD are the major polyamines (PAs) conjugated to macromolecules, mainly to high molecular mass glycoproteins. The disease was associated to an increase in total PA fraction. Arginase and ornithine decarboxylase activities, responsible for the synthesis of PUT, were higher in YLS juices than in those obtained from healthy plants. CAD and SPM presumably conjugated mostly to chlorogenic, syringic and ferulic acids in juices from YLS plants.

Smut is a major disease of sugarcane caused by Ustilago scitaminea. Germination of fungal teliospores is achieved on the internode surface of plants, and it is followed by the formation of appressoria. A primary response of sugarcane plants to the infection seems to be the production of several glycoproteins, defined as mid-molecular mass (MMMG) or high molecular mass (HMMG) macromolecules. Teliospore germination in the presence of both MMMG and HMMG decreased about 50% following 5 h of teliospore contact with glycoproteins. This may be related to the ability of glycoproteins to produce cytoagglutination. Binding of fluorescein-labelled glycoproteins was studied by fluorescence microscopy, showing that staining of cells was not uniform, but mainly in the contact zone between two individual teliospores when aggregated. HMMG was composed of only one fraction that was completely retained by smut teliospores, whereas three of the five different glycoproteins occurring in the MMMG fraction were retained by teliospore cell walls. Moreover, a unique application of salicylic acid, naturally produced by sugarcane stalks after experimental fungal infection, enhanced the production of both glycoprotein pools. A hypothesis about the role of both HMMG and MMMG as defence glycoproteins is discussed.

Two different pools of glycoproteins, tentatively described as high and mid-molecular mass polymers, are currently separated by conventional gel filtration. Anion-exchange chromatography on DEAE-Sephadex A-60 discriminates between neutral or cationic, and anionic polymers composing both fractions. The occurrence of both cationic and anionic glycoproteins has been corroborated after separation by capillary electrophoresis. Total or partial digestion of the glycosidic moiety of these glycoproteins using β-1,2-fructofuranosidase reveals that cationic species from the mid molecular mass glycoproteins move to the neutral or anionic zone of the electropherogram whereas only one cationic form from high molecular mass polymers remains unchanged after enzymatic hydrolysis of the glycosidic moiety. This indicates that this moiety is able to modify the net charge of some of the mid-molecular mass glycoproteins whereas the net charge of cationic high molecular mass polymer can be due to the own protein moiety or, probably, to some polycationic polyamines bound on this moiety.

We have performed a phase II study to evaluate the activity and toxicity of ifosfamide and cisplatin as first-line treatment for advanced ovarian cancer. Patients were treated with cisplatin 100 mg/m 2 on day 1 and ifosfamide 5 g/m 2 in 18-hr continuous infusion on day 1 or 1.5 g/m 2 bolus on days 1–5. Between August 1988 and March 1990, 30 women were entered in the trial, 26 of them with measurable disease. The overall clinical response rate was 69% (95% CI: 48–85%), including 34.6% complete responses (95% CI:17–55%). Reassessment laparotomy was performed in 12 cases, and 4 (33%) exhibited a pathologic complete response. For all patients, the median duration of progression-free survival was 14 months, and the median overall survival was 25 months. There were no major differences in the response rate or survival between the two ifosfamide administration modalities. Relevant toxicities were grade IV hematologic toxicity in 11/30 patients and grade IV renal toxicity in 2/30 patients. A patient with grade IV encephalopathy developed a trauma-related cerebral hemorrhage and died 2 months later. The combination of ifosfamide and cisplatin is active in first-line therapy in advanced ovarian cancer, although it does not seem to improve the efficacy or toxicity profile of conventional combinations.

The Brazilian gray short-tailed opossum is a pouchless marsupial whose young are born sexually undifferentiated making this animal ideal for developmental studies. Previously, Etgen and Fadem ( Dev. Brain Res. , 49 (1989) 131–133; Gen. Comp. Endocrinol. , 66 (1987) 441–446) detected estrogen receptor (ER) in the hypothalamus-preoptic area, and compared males and females in the adult and during development. In this study we characterized the ER and determined its distribution in specific diencephalic regions in the brains of adult male and female opossums. ER were measured by the in vitro binding of [ 3 H]estradiol to cytosol of microdissected brain nuclear regions. Radioinert moxestrol (R2858) was used to define non-specific binding. Saturation analysis showed a single high-affinity binding site. Binding was displaced by estradiol (E 2 ), diethylstilbestrol (DES) and R2858, but not by non-estrogenic steroids. Ligand bound receptor adhered to DNA-cellulose and was eluted as a single peak with 0.2–0.3 M NaCl. High levels of ER were found in the medial preoptic-periventricular area. Intermediate levels were seen in the ventromedial hypothalamic nucleus, medial amygdala and arcuate nucleus. No sex differences were observed. The presence of a neural ER and its similarity of distribution to that of the laboratory rat support the use of this animal model in studies examining steroid dependent organization of the hypothalamus.

Sugar cane accumulates in its stalks sucrose and, later, polysaccharides including fructans. These polysaccharides are hydrolyzed by a fructanase which requires Mn 2+ to act. Since these fructans are heteropolymers containing both fructose and galactitol, the enzyme must contain at least two different hydrolase activities. During the first 2 days of post-collection impairment, fructanase activity rapidly develops and, then, it decreases and stabilizes. The decrease in the amount of mid-molecular weight carbohydrates after the fourth day of post-collection impairment can be seen as a consequence of the stabilization of fructanase activity. This hydrolase is inhibited by an excess of Mn 2+ as well as by reducing sugars accumulated in the juices.

Background S-1, a new generation of oral fluoropyrimidine, is active against Advanced Gastric Cancer (AGC). The primary analysis of FLAGS (JCO 2010; vol.28 p 1547-53) did not show any differences in overall survival (OS) between CS and CF. S-1 has been registered in Europe, with supportive analyses including non-inferiority (NI) analysis. Methods 1,053 (1,029 treated; CS = 521/CF = 508) patients (non Asian 88 + %) with untreated, advanced gastric (83.1 %) / gastroesophageal (16.5%) adenocarcinoma were randomized to either S-1 (25 mg/m2 bid, d 1-21)/cisplatin (75 mg/m2 d 1) q 28 d or 5-FU (1,000 mg/m2/d1-5 infusion)/cisplatin (100 mg/m2 d 1) q 28 d. OS analyses for non-inferiority, by pre-specified stratifications, were performed. Results OS for NI from CS (8.6 months) compared to CF (7.9 months) had a HR = 0.92 (two-sided 95% CI, 0.80-1.05). HR = 1.05 being lower than HR = 1.10 non inferiority margin, derived from a literature meta-analysis, CS remains statistically significantly non-inferior (p = 0.0068) to CF. The 74% preserved control effect by CS is well above the suggested 50% by Rothmann et al. (Statist-Med2003; 22:239-264), based on which the 1.10 non-inferiority margin was derived. Moreover, statistically significant safety advantages for the CS arm were observed for the rates of G3/4 neutropenia (18.6%, CS; 40.0%, CF), G3/4 febrile neutropenia (1.7%, CS; 6.9%, CF), G3/4 stomatitis (1.3%, CS; 13.6%, CF), renal adverse events (all grades: 18.8%, CS; 33.5%, CF), and severe hypokalemia (3.6%, CS; 10.8%, CF). On the other safety items, no significant differences were noted between CS and CF, especially regarding Head and Foot Syndrome which was anecdotal and limited to grade 1/2. Treatment-related deaths were significantly reduced with CS compared to CF (respectively 2.5% and 4.9%). Conclusion CS is non-inferior to CF while providing safety advantages for the patients and is a treatment alternative in advanced gastric carcinoma. Disclosure All authors have declared no conflicts of interest.

Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. Disclosure All authors have declared no conflicts of interest.

Proximal and distal lithogeochemical alteration patterns associated with precious-metal and polymetallic vein mineralization in the Andes of Bolivia and Peru are delineated both by sulphophile elements such as Ag, As, Pb, S, Sb, Sn and Zn, and also by hydrothermal alteration indicators such as CaO/MgO, K2O/Na2O, Rb/K and Rb/Sr. In some cases, single-element, ratio and normalized data additive plots permit the detection of a vein at a distance of more than 100 m even when the visible alteration extends for less than 10 m. Asymmetric hanging-wall-footwall halos in both volcanic and sedimentary rocks provide a useful supra-ore/sub-ore indicator for inclined veins. The K2O/Na2O ratio appears to be the most reliable lithogeochemical guide to ore-related hydrothermal alteration.