First countrywide survey of third-generation cephalosporin-resistant Escherichia coli from broilers, swine, and cattle in Switzerland

The herd prevalence of third-generation cephalosporin-resistant Escherichia coli (3GC-R-Ec) was determined for broilers (25.0% [95% confidence interval (CI) 17.6-33.7%]), pigs (3.3% [(95% CI 0.4-11.5%]), and cattle (3.9% [95% CI 0.5-13.5%]), using a sampling strategy that was representative of the livestock population slaughtered in Switzerland between October 2010 and April 2011. The 3GC-R-Ec isolates were characterized by the measurement of the MICs of various antibiotics, microarray analyses, analytical isoelectric focusing, polymerase chain reaction and DNA sequencing for bla genes, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing. CMY-2 (n = 12), CTX-M-1 (n = 11), SHV-12 (n = 5), TEM-52 (n = 3), CTX-M-15 (n = 2), and CTX-M-3 (n = 1) producers were found. The majority of CMY-2 producers fell into 1 PFGE cluster, which predominantly contained ST61, whereas the CTX-M types were carried by heterogeneous clones of E. coli, as shown by the numerous PFGE profiles and STs that were found. This is the first national Swiss study that focuses on the spread of 3GC-R Enterobacteriaceae among slaughtered animals.

Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome

OBJECTIVES: We sought to determine both the procedural performance and safety of percutaneous implantation of the second (21-French [F])- and third (18-F)-generation CoreValve aortic valve prosthesis (CoreValve Inc., Irvine, California). BACKGROUND: Percutaneous aortic valve replacement represents an emerging alternative therapy for high-risk and inoperable patients with severe symptomatic aortic valve stenosis. METHODS: Patients with: 1) symptomatic, severe aortic valve stenosis (area <1 cm2); 2) age > or =80 years with a logistic EuroSCORE > or =20% (21-F group) or age > or =75 years with a logistic EuroSCORE > or =15% (18-F group); or 3) age > or =65 years plus additional prespecified risk factors were included. Introduction of the 18-F device enabled the transition from a multidisciplinary approach involving general anesthesia, surgical cut-down, and cardiopulmonary bypass to a truly percutaneous approach under local anesthesia without hemodynamic support. RESULTS: A total of 86 patients (21-F, n = 50; 18-F, n = 36) with a mean valve area of 0.66 +/- 0.19 cm2 (21-F) and 0.54 +/- 0.15 cm2 (18-F), a mean age of 81.3 +/- 5.2 years (21-F) and 83.4 +/- 6.7 years (18-F), and a mean logistic EuroSCORE of 23.4 +/- 13.5% (21-F) and 19.1 +/- 11.1% (18-F) were recruited. Acute device success was 88%. Successful device implantation resulted in a marked reduction of aortic transvalvular gradients (mean pre 43.7 mm Hg vs. post 9.0 mm Hg, p < 0.001) with aortic regurgitation grade remaining unchanged. Acute procedural success rate was 74% (21-F: 78%; 18-F: 69%). Procedural mortality was 6%. Overall 30-day mortality rate was 12%; the combined rate of death, stroke, and myocardial infarction was 22%. CONCLUSIONS: Treatment of severe aortic valve stenosis in high-risk patients with percutaneous implantation of the CoreValve prosthesis is feasible and associated with a lower mortality rate than predicted by risk algorithms.

Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

Light curing through glass ceramics with a second- and a third-generation LED curing unit: effect of curing mode on the degree of conversion of dual-curing resin cements

Objectives The aim of this study was to measure the degree of conversion (DC) of five dual-curing resin cements after different curing modes with a second- and a third-generation light-emitting diode (LED) curing unit. Additionally, irradiance of both light curing units was measured at increasing distances and through discs of two glass ceramics for computer-aided design/manufacturing (CAD/CAM). Materials and methods Irradiance and spectra of the Elipar FreeLight 2 (Standard Mode (SM)) and of the VALO light curing unit (High Power Mode (HPM) and Xtra Power Mode (XPM)) were measured with a MARC radiometer. Irradiance was measured at increasing distances (control) and through discs (1.5 to 6 mm thickness) of IPS Empress CAD and IPS e.max CAD. DC of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA was measured with an attenuated total reflectance–Fourier transform infrared spectrometer when self-cured (negative control) or light cured in SM for 40 s, HPM for 32 s, or XPM for 18 s. Light curing was performed directly (positive control) or through discs of either 1.5- or 3-mm thickness of IPS Empress CAD or IPS e.max CAD. DC was analysed with Kruskal–Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). Results Maximum irradiances were 1,545 mW/cm2 (SM), 2,179 mW/cm2 (HPM), and 4,156 mW/cm2 (XPM), and all irradiances decreased by >80 % through discs of 1.5 mm, ≥95 % through 3 mm, and up to >99 % through 6 mm. Generally, self-curing resulted in the lowest DC. For some cements, direct light curing did not result in higher DC compared to when light cured through ceramic discs. For other cements, light curing through ceramic discs of 3 mm generally reduced DC. Conclusions Light curing was favourable for dual-curing cements. Some cements were more susceptible to variations in curing mode than others. Clinical relevance When light curing a given cement, the higher irradiances of the third-generation LED curing unit resulted in similar DC compared to the second-generation one, though at shorter light curing times.

Occurrence and Genetic Characteristics of Third-Generation Cephalosporin-Resistant Escherichia coli in Swiss Retail Meat

Prevalence and genetic relatedness were determined for third-generation cephalosporin-resistant Escherichia coli (3GC-R-Ec) detected in Swiss beef, veal, pork, and poultry retail meat. Samples from meat-packing plants (MPPs) processing 70% of the slaughtered animals in Switzerland were purchased at different intervals between April and June 2013 and analyzed. Sixty-nine 3GC-R-Ec isolates were obtained and characterized by microarray, PCR/DNA sequencing, Multi Locus Sequence Typing (MLST), and plasmid replicon typing. Plasmids of selected strains were transformed by electroporation into E. coli TOP10 cells and analyzed by plasmid MLST. The prevalence of 3GC-R-Ec was 73.3% in chicken and 2% in beef meat. No 3GC-R-Ec were found in pork and veal. Overall, the blaCTX-M-1 (79.4%), blaCMY-2 (17.6%), blaCMY-4 (1.5%), and blaSHV-12 (1.5%) β-lactamase genes were detected, as well as other genes conferring resistance to chloramphenicol (cmlA1-like), sulfonamides (sul), tetracycline (tet), and trimethoprim (dfrA). The 3GC-R-Ec from chicken meat often harbored virulence genes associated with avian pathogens. Plasmid incompatibility (Inc) groups IncI1, IncFIB, IncFII, and IncB/O were the most frequent. A high rate of clonality (e.g., ST1304, ST38, and ST93) among isolates from the same MPPs suggests that strains persist at the plant and spread to meat at the carcass-processing stage. Additionally, the presence of the blaCTX-M-1 gene on an IncI1 plasmid sequence type 3 (IncI1/pST3) in genetically diverse strains indicates interstrain spread of an epidemic plasmid. The blaCMY-2 and blaCMY-4 genes were located on IncB/O plasmids. This study represents the first comprehensive assessment of 3GC-R-Ec in meat in Switzerland. It demonstrates the need for monitoring contaminants and for the adaptation of the Hazard Analysis and Critical Control Point concept to avoid the spread of multidrug-resistant bacteria through the food chain.

Search for direct third-generation squark pair production in final states with missing transverse momentum and two b-jets in sqrts = 8 TeV pp collisions with the ATLAS detector

The results of a search for pair production of supersymmetric partners of the Standard Model third-generation quarks are reported. This search uses 20.1 fb(-1) of pp collisions at root s = 8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The lightest bottom and top squarks ((b) over tilde (1) and (t) over tilde (1) respectively) are searched for in a final state with large missing transverse momentum and two jets identified as originating from b-quarks. No excess of events above the expected level of Standard Model background is found. The results are used to set upper limits on the visible cross section for processes beyond the Standard Model. Exclusion limits at the 95% confidence level on the masses of the third-generation squarks are derived in phenomenological supersymmetric R-parity-conserving models in which either the bottom or the top squark is the lightest squark. The (b) over tilde (1) is assumed to decay via (b) over tilde (1) -> b (chi) over tilde (0)(1) and the (t) over tilde (1) via (t) over tilde (1) b (chi) over tilde (+/-)(1), with undetectable products of the subsequent decay of the (chi) over tilde (+/-)(1) due to the small mass splitting between the (chi) over tilde (+/-)(1) and the (chi) over tilde (0)(1)

Search for third generation scalar leptoquarks in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

A search for pair-produced third generation scalar leptoquarks is presented, using proton-proton collisions at root s = 7 TeV at the LHC. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 4.7 fb(-1). Each leptoquark is assumed to decay to a tau lepton and a b-quark with a branching fraction equal to 100%. No statistically significant excess above the Standard Model expectation is observed. Third generation leptoquarks are therefore excluded at 95% confidence level for masses less than 534 GeV.

Search for pair and single production of new heavy quarks that decay to a ℤ boson and a third-generation quark in pp collisions at √ s=8 TeV with the ATLAS detector

A search is presented for the production of new heavy quarks that decay to a Z boson and a third-generation Standard Model quark. In the case of a new charge +2/3 quark (T), the decay targeted is T → Zt, while the decay targeted for a new charge −1/3 quark (B) is B → Zb. The search is performed with a dataset corresponding to 20.3 fb−1 of pp collisions at √ s = 8TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider. Selected events contain a high transverse momentum Z boson candidate reconstructed from a pair of oppositely charged same-flavor leptons (electrons or muons), and are analyzed in two channels defined by the absence or presence of a third lepton. Hadronic jets, in particular those with properties consistent with the decay of a b-hadron, are also required to be present in selected events. Different requirements are made on the jet activity in the event in order to enhance the sensitivity to either heavy quark pair production mediated by the strong interaction, or single production mediated by the electroweak interaction. No significant excess of events above the Standard Model expectation is observed, and lower limits are derived on the mass of vector-like T and B quarks under various branching ratio hypotheses, as well as upper limits on the agnitude of electroweak coupling parameters.

Search for pair-produced third-generation squarks decaying via charm quarks or in compressed supersymmetric scenarios in pp collisions at √s=8 TeV with the ATLAS detector

Results of a search for supersymmetry via direct production of third-generation squarks are reported, using 20.3  fb −1 of proton-proton collision data at √s =8  TeV recorded by the ATLAS experiment at the LHC in 2012. Two different analysis strategies based on monojetlike and c -tagged event selections are carried out to optimize the sensitivity for direct top squark-pair production in the decay channel to a charm quark and the lightest neutralino (t 1 →c+χ ˜ 0 1 ) across the top squark–neutralino mass parameter space. No excess above the Standard Model background expectation is observed. The results are interpreted in the context of direct pair production of top squarks and presented in terms of exclusion limits in the m ˜t 1, m ˜ X0 1 ) parameter space. A top squark of mass up to about 240 GeV is excluded at 95% confidence level for arbitrary neutralino masses, within the kinematic boundaries. Top squark masses up to 270 GeV are excluded for a neutralino mass of 200 GeV. In a scenario where the top squark and the lightest neutralino are nearly degenerate in mass, top squark masses up to 260 GeV are excluded. The results from the monojetlike analysis are also interpreted in terms of compressed scenarios for top squark-pair production in the decay channel t ˜ 1 →b+ff ′ +χ ˜ 0 1 and sbottom pair production with b ˜ 1 →b+χ ˜ 0 1 , leading to a similar exclusion for nearly mass-degenerate third-generation squarks and the lightest neutralino. The results in this paper significantly extend previous results at colliders.

Third-Generation-Cephalosporin-Resistant Klebsiella pneumoniae Isolates from Humans and Companion Animals in Switzerland: Spread of a DHA-Producing Sequence Type 11 Clone in a Veterinary Setting.

Characterization of third-generation-cephalosporin-resistant Klebsiella pneumoniae isolates originating mainly from one human hospital (n = 22) and one companion animal hospital (n = 25) in Bern (Switzerland) revealed the absence of epidemiological links between human and animal isolates. Human infections were not associated with the spread of any specific clone, while the majority of animal infections were due to K. pneumoniae sequence type 11 isolates producing plasmidic DHA AmpC. This clonal dissemination within the veterinary hospital emphasizes the need for effective infection control practices.

Comparative immunogenicity of a PreS/S hepatitis B vaccine in non- and low responders to conventional vaccine

Conventional hepatitis B vaccines do not elicit adequate antibody production in 5-10% vaccinees. This trial tests the ability of a third-generation vaccine, containing PreS1 and PreS2 antigens in addition to the S antigen, to elicit seroprotective titres in documented non- and low-responders, compared with those to a conventional vaccine. In the primary population of non-responders (<10 IU/l anti-HBs antibodies after > or = 4 previous injections of conventional vaccine) an enhanced antibody response was seen to additional injections of the third-generation vaccine compared with a conventional vaccine (absolute difference 14.9%; P = 0.006). Enhanced antibody responses were also found in a population that included low responders.

X-ray phase contrast imaging of metallized and non-metallized biological samples

Imaging of biological samples has been performed with a variety of techniques for example electromagnetic waves, electrons, neutrons, ultrasound and X-rays. Also conventional X-ray imaging represents the basis of medical diagnostic imaging, it remains of limited use in this application because it is based solely on the differential absorption of X-rays by tissues. Coherent and bright photon beams, such as those produced by third-generation synchrotron X-ray sources, provide further information on subtle X-ray phase changes at matter interfaces. This complements conventional X-ray absorption by edge enhancement phenomena. Thus, phase contrast imaging has the potential to improve the detection of structures on images by detecting those structures that are invisible with X-ray absorption imaging. Images of a weakly absorbing nylon fibre were recorded in in-line holography geometry using a high resolution low-noise CCD camera at the ESRF in Grenoble. The method was also applied to improve image contrast for images of biological tissues. This paper presents phase contrast microradiographs of vascular tree casts and images of a housefly. These reveal very fine structures, that remain invisible with conventional absorption contrast only.

Different amino acid substitutions at the same position in rhodopsin lead to distinct phenotypes

PURPOSE: Identification of a novel rhodopsin mutation in a family with retinitis pigmentosa and comparison of the clinical phenotype to a known mutation at the same amino acid position. METHODS: Screening for mutations in rhodopsin was performed in 78 patients with retinitis pigmentosa. All exons and flanking intronic regions were amplified by PCR, sequenced, and compared to the reference sequence derived from the National Center for Biotechnology Information (NCBI, Bethesda, MD) database. Patients were characterized clinically according to the results of best corrected visual acuity testing (BCVA), slit lamp examination (SLE), funduscopy, Goldmann perimetry (GP), dark adaptometry (DA), and electroretinography (ERG). Structural analyses of the rhodopsin protein were performed with the Swiss-Pdb Viewer program available on-line (http://www.expasy.org.spdvbv/ provided in the public domain by Swiss Institute of Bioinformatics, Geneva, Switzerland). RESULTS: A novel rhodopsin mutation (Gly90Val) was identified in a Swiss family of three generations. The pedigree indicated autosomal dominant inheritance. No additional mutation was found in this family in other autosomal dominant genes. The BCVA of affected family members ranged from 20/25 to 20/20. Fundus examination showed fine pigment mottling in patients of the third generation and well-defined bone spicules in patients of the second generation. GP showed concentric constriction. DA demonstrated monophasic cone adaptation only. ERG revealed severely reduced rod and cone signals. The clinical picture is compatible with retinitis pigmentosa. A previously reported amino acid substitution at the same position in rhodopsin leads to a phenotype resembling night blindness in mutation carriers, whereas patients reported in the current study showed the classic retinitis pigmentosa phenotype. The effect of different amino acid substitutions on the three-dimensional structure of rhodopsin was analyzed by homology modeling. Distinct distortions of position 90 (shifts in amino acids 112 and 113) and additional hydrogen bonds were found. CONCLUSIONS: Different amino acid substitutions at position 90 of rhodopsin can lead to night blindness or retinitis pigmentosa. The data suggest that the property of the substituted amino acid distinguishes between the phenotypes.

Estrogen receptor modulators and down regulators: optimal use in postmenopausal women with breast cancer

Endocrine treatments have been used in breast cancer since 1896, when Beatson reported on the results of oophorectomy for advanced breast cancer. In the second half of the last century, different endocrine-based compounds were developed and, in this review, the role of the selective estrogen receptor modulators (SERMs) and selective estrogen receptor down regulators (SERDs) in the postmenopausal setting are discussed. Tamoxifen is the most investigated and most widely used representative of these agents, and has been introduced in the advanced disease, in the neoadjuvant and adjuvant setting, and for the prevention of the disease. Its role has been challenged in recent years by the introduction of third-generation aromatase inhibitors that have proven higher activities than tamoxifen with different toxicity patterns. Several other SERMs have been investigated, but none have been clearly superior to tamoxifen. SERDs act as pure estrogen antagonists and should compare favourably to tamoxifen. For the time being, they have been used in the treatment of advanced breast cancers and their role in other settings still needs investigation. The increased use of aromatase inhibitors as first-line endocrine therapy has resulted in new discussions regarding the role that tamoxifen and other SERMs or SERDs may play in breast cancer. The sequencing of endocrine therapies in hormone-sensitive breast cancer remains a very important research issue.

Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

PURPOSE: Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority. METHODS: Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. RESULTS: All peptides showed high affinities on hsst2, with the highest affinity for the Ga(III)-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga(III) peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1-Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and receptor-mediated uptake of the two 67Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide. CONCLUSION: This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies.