A genome-wide association study for left-sided displacement of the abomasum using a high-density single nucleotide polymorphism array.

Left-sided displacement of the abomasum (LDA) is a frequent disease in dairy cattle causing significant financial losses for dairy farmers. Heritability (h2) of this complex disease was estimated at up to 0.5 in German Holstein (GH) cattle. Using the Bovine High Density BeadChip (Illumina Inc., San Diego, CA) comprising 588,753 single nucleotide polymorphisms (SNP) after quality control for 126 LDA cases and 280 population-based controls, we used a mixed linear model analysis in a genome-wide association study (GWAS). We identified 6 genomic regions for LDA on bovine chromosomes 2, 8, 13, 20, 24, and X that were significantly associated with LDA. Each of these regions was covered by 4 to 12 LDA-associated SNP. Single SNP within these regions explained up to 7.3% of the phenotypic variance. An independent sample of 1,554 GH cows, including 539 controls and 1,015 cases, were genotyped for 8 SNP highly associated with LDA on Bos taurus autosomes (BTA) 2, 8, 13, and 24, as well as 6 SNP located in previously identified LDA regions on BTA1, 5, 11, and 27 using competitive allele-specific PCR genotyping technology (KASP). The analysis using the KASP genotypes confirmed LDA-associated loci on BTA2, 8, 13, and 27. These genomic regions may contribute to the susceptibility to LDA in Holstein cows and may harbor functional variants for LDA.

Robust evidence for long-term survival with 90Y radioembolization in chemorefractory liver-predominant metastatic colorectal cancer.

OBJECTIVES: Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). METHODS: We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. RESULTS: Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. CONCLUSIONS: After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. KEY POINTS: • After multiple chemotherapies, many patients are still eligible for radioembolization (RE). • RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC). • Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE. • Radioembolization in patients with a good performance status is generally well tolerated.

Safety of Radioembolization with (90)Yttrium Resin Microspheres Depending on Coiling or No-Coiling of Aberrant/High-Risk Vessels.

PURPOSE: To evaluate the safety of radioembolization (RE) with (90)Yttrium ((90)Y) resin microspheres depending on coiling or no-coiling of aberrant/high-risk vessels. MATERIALS AND METHODS: Early and late toxicity after 566 RE procedures were analyzed retrospectively in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v3.0). For optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling group) or a more peripheral position of the catheter tip was chosen to treat right or left liver lobes (n = 326/566, no-coiling group). RESULTS: Clinically relevant late toxicities (≥ Grade 3) were observed in 1% of our overall cohort. The no-coiling group had significantly less "any" (P = 0.0001) or "clinically relevant" (P = 0.0003) early toxicity. There was no significant difference (P > 0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE-induced liver disease was noted after all 566 procedures. CONCLUSION: RE with (90)Y resin microspheres is a safe and effective treatment option. Performing RE without coil embolization of aberrant vessels prior to treatment could be an alternative for experienced centers.

A moiré deflectometer for antimatter.

The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics--the moiré deflectometer--for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter.

[Musculoskeletal modeling of the patellofemoral joint. Dynamic analysis of patellar tracking]. / Muskuloskelettale Modellierung des patellofemoralen Gelenks. Dynamische Analyse der patellaren Führung.

Numerical simulations contribute to the understanding of patellofemoral diseases. Whereas cadaveric studies are limited with respect to reproducibility of results, the impact of different operative approaches can be systematically evaluated based on mathematical models. The objective of this study was to introduce a musculoskeletal model which is capable of describing the dynamic interactions within the patellofemoral joint. It contains major bony and soft tissue structures of the right leg including the medial patellofemoral ligament (MPFL). Two operative approaches were considered based on the model to illustrate the effect on patellofemoral biomechanics during active knee flexion: On the one hand the effect of femoral insertion during MPFL reconstruction on medial soft tissue tension, and on the other hand the difference in patella kinematics before and after total knee arthroplasty. Finally, the potential of musculoskeletal models is discussed.

Combined anatomical and functional imaging using coronary CT angiography and myocardial perfusion SPECT in symptomatic adults with abnormal origin of a coronary artery.

There has been a lack of standardized workup guidelines for patients with congenital abnormal origin of a coronary artery from the opposite sinus (ACAOS). We aimed to evaluate the use of cardiac hybrid imaging using multi-detector row CT (MDCT) for coronary CT angiography (Coronary CTA) and stress-rest myocardial perfusion SPECT (MPS) for comprehensive diagnosis of symptomatic adult patients with ACAOS. Seventeen symptomatic patients (12 men; 54 ± 13 years) presenting with ACAOS underwent coronary CTA and MPS. Imaging data were analyzed by conventional means, and with additional use of 3D image fusion to allocate stress induced perfusion defects (PD) to their supplying coronary arteries. An anomalous RCA arose from the left anterior sinus in eight patients, an abnormal origin from the right sinus was detected in nine patients (5 left coronary arteries, LCA and 4 LCx). Five of the 17 patients (29%) demonstrated a reversible PD in MPS. There was no correlation between the anatomical variants of ACAOS and the presence of myocardial ischemia. Image fusion enabled the allocation of reversible PD to the anomalous vessel in three patients (two cases in the RCA and the other in the LCA territory); PD in two patients were allocated to the territory of artery giving rise to the anomalies, rather than the anomalies themselves. In a small cohort of adult symptomatic patients with ACAOS anomaly there was no relation found between the specific anatomical variant and the appearance of stress induced myocardial ischemia using cardiac hybrid imaging.

Evaluation of LC-high-resolution FT-Orbitrap MS for the quantification of selected mycotoxins and the simultaneous screening of fungal metabolites in food.

A liquid chromatography-high-resolution mass spectrometry-based method is reported for the quantification of 20 selected mycotoxins and the simultaneous screening for 200 fungal metabolites in food. For regulated mycotoxins, such as aflatoxins, fumonisins, ochratoxin A, zearalenone and trichothecenes, the evaluation of the method performance characteristics, such as precision, trueness, limit of detection and matrix effects, has been exemplified for the matrix maize. In the case of the limit of detection, an alternative evaluation approach for high-resolution FT-Orbitrap data is proposed. Measurements of the signal-to-noise ratios obtained from 'full-profile mode' data led to detection limits between 8 and 160 ng g(-1). Eight naturally contaminated wheat- and maize-based matrix test materials, originating from interlaboratory comparison studies, were used to confirm the trueness of the method for deoxynivalenol, zearalenone, fumonisin B(1) and B(2), HT-2, and T-2 toxin. In addition to accurate quantification of the most relevant mycotoxins, the full-scan chromatograms were used to investigate the potential of the FT-Orbitrap to screen simultaneously for a large number of fungal metabolites. First, a list of 200 metabolites, potentially being present in food samples, was established. Next, specific detection and identification criteria were defined, which are based on accurate mass, peak intensity and isotopologue ratio. The application of these criteria to the suspected metabolites from the list resulted in the putative identification of 13 fungal metabolites in addition to the target toxins.

[Relevance of ESBL-producing pathogens for clinical surgery: diagnostics, therapy, and prevention]. / Bedeutung ESBL-produzierender Keime für die klinische Chirurgie : Diagnostik, Prävention und Therapie.

BACKGROUND: Multiresistant, extended spectrum beta lactamase (ESBL)-producing pathogens are an increasing problem in daily clinical life. This paper summarizes the development of resistance as well as epidemiology, diagnostics, and treatment of ESBL-producing micro-organisms. We analyzed microbiological data collected at the Grosshadern Clinic in Germany between 1996 and 2007, in order to assess the importance of these micro-organisms to medical practice and surgical care units. PATIENTS AND METHODS: Pathogens were isolated from 28,894 patients with Escherichia coli and 10,903 with Klebsiella pneumoniae pathogens between 1996 and 2006 and tested for ESBL production. For the year 2007 we have analyzed the complete spectrum of ESBL-producing pathogens and their distribution to different departments of the clinic. The agar diffusion test with five cephalosporins and an automated detection system (BD Phoenix) were used for screening purposes. Positive results were verified with the E- and double-disc agar diffusion tests. RESULTS: The most important pathogens isolated from patients were E. coli and K. pneumoniae. Analysis of ESBL-producing E. coli pathogens from 1996 to 2006 showed the prevalence increasing from 0% to 4.1%. For ESBL-producing K. pneumoniae, we also found a prevalence rising from 0.3% in 1996 to 6.6% in 2006. For the year 2007 a further increase in ESBL-producing pathogens was detected, reaching 182 cases, with 118 of ESBL-producing E. coli (5.7 %) and 39 of ESBL-producing K. pneumoniae (7.4%). Of these, 24 cases with E. coli and nine with K. pneumoniae were surgery patients (20% and 23%, respectively). CONCLUSION: The results show an increasing prevalence of ESBL-producing pathogens in hospitalized patients and in surgical departments. The resulting rise in treatment costs and patient risk require thorough knowledge of risk factors, therapy, and preventive measures.

Comparing biomechanical investigations about different wiring techniques of finger joint arthrodesis.

INTRODUCTION: Multiple operative techniques are currently used for finger arthrodesis in clinical practice. The present study was designed to compare the biomechanical characteristics of typical arthrodesis techniques used in daily practice. MATERIAL AND METHODS: Osteosynthesis techniques comprising wire cerclage, thread cerclage (PDS) or intraosseous wire suture were compared in a biomechanical experiment for resistance against bending loads. The mentioned techniques were applied to artificial specimens with resected articular surfaces or by using the cup-and-cone procedure. In this process, the specimens were tested using various Kirschner-wire insertion angles as well as different arthrodesis angles (20 degrees vs 40 degrees) in a 4-point bending test with each group consisting of 6 specimens of acrylic glass. The forces prevalent in the joint space were determined by prescale pressure measurement foils. RESULTS: Wire tension banding resisted significantly higher bending moments than arthrodeses with thread tension bands (p < 0.05). All set-ups with tension banding techniques tolerated significantly higher loads than the intraosseous wire sutures without additional K-wires (p < 0.05), which showed unfavorable dislocation of contact areas resulting in instability even under relatively minor bending loads. Using the cup-and-cone technique, a geometrically larger contact area could be achieved between two unloaded fragments, but this technique showed no advantages in the opposing bending moments compared with the conventional resection method. In both techniques, a dislocation of contact surfaces towards the palmar direction could be observed with increasing bending moment. While the use of thread tension band fixation reduces the risk of plastic deformation of both osteosynthetic material and bone stock, the problem of resorption rate has to be taken into account when choosing the material for the thread. CONCLUSIONS: Considering pressure distribution and stability with and without bending loads, it is not the most rigid osteosynthesis technique which should be viewed as the ideal treatment. In contrast, it is more important to consider the various and most likely conditions to be expected in daily life after arthrodesis and therefore to chose the type of technique distributing pressure as regularly as possible.

BISS: concept and biomechanical investigations of a new screw system for electromagnetically induced internal osteostimulation.

INTRODUCTION: The aim of an intraosseous application of electromagnetic alternating fields is to speed up both the regeneration of osteonecroses and bone regeneration. In clinical studies, the efficiency of the technique could be successfully proven by using a transducer coil. The advantage of the traditional technique was the variety of its applications in connection with various osteosynthesis systems; the disadvantage was a possible failure of the contacting leads and the resulting functional breakdown. MATERIALS AND METHODS: A newly developed BISS screw (bipolar induction screw system) with integrated coil and electrodes was compared to a standard cannulated screw used in the traditional technique. The strength of BISS screws ( n=6) and of cannulated screws ( n=6) was evaluated in comparative biomechanical tests. Examinations consisted of torsional and static and dynamic cantilever tests. All screws were made of the same material (TiAl(6)V(4)) and had identical outer dimensions. RESULTS: No significantly lower strengths could be observed when we compared BISS screws with cannulated screws. The BISS screws even showed significantly higher mechanical values due to a reinforcing effect by the attached electrode. CONCLUSION: In the modified concept of the new BISS screw, both coil and electrodes are housed in only one cannulated screw. No negative effects concerning mechanical strength and durability were associated with the new screw concept. This provides for a simpler implantation and makes removal easier, while the risk of a cable tear is avoided.

[New compounds for improving wear behavior of a tumor knee endoprosthesis]. / Neue Werkstoffpaarungen zur Verbesserung des Verschleissverhaltens einer Tumor-Knieendoprothese.

Wear of the central bushing made of ultra-high molecular weight polyethylene (PE-UHMW) of the hinged knee endoprosthesis of a tumour-resection system is the leading reason for revision. The aim of the study was to optimize the wear characteristics of the endoprosthesis on the basis of the tribological properties of new materials and an additional finite element (FE) calculation taking account of the given design. In screening tests the reference combination of PE-UHMW bushing and CoCr axis--used in the clinical setting--was first tested. The PE-UHMW bushing was then replaced by one made of each of the materials reinforced high-density polyethylene (PE-HD) and carbon fibre-reinforced epoxy resin (CFRP). In addition, a new material combination with an alumina ceramic bushing and a CFRP axis was investigated. In comparison with the reference combination PE-UHMW/metal, the combination of ceramic bushing and CFRP axis showed less wear. However, with the particular design of the prosthesis studied here, high mechanical loading applied experimentally resulted in mechanical failure. FE calculations confirmed these experimental results. Improvement of the wear characteristics of this specific implant caused therefore be achieved only by optimizing the bearing design.

Effect of hydroxypropyl-beta-cyclodextrin on the antimicrobial action of preservatives.

The interaction between hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and several preservatives with different chemical structures was investigated in aqueous solution. Complex stability constants of the 1:1 complexes were calculated from differential spectra. Using the serial dilution test the antimicrobial activities of the preservatives and their complexes against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans were tested and MIC values determined. For highly water-soluble substances like thimerosal and bronopol, low or no inactivation was found; the more lipophilic substances, such as the phenolic compounds, showed strong inactivation when used in combination with HP-beta-CyD. The loss in activity by complex formation correlated with the bound fraction, thus suggesting that the appropriate antimicrobial substance for the preservation of cyclodextrin solutions can be selected according to the results of this study.

[Enlarged spectrum of tick transmitted spirochaetoses]. / Zum erweiterten Spektrum zeckenübertragener Spirochätosen.

After the successful identification of Borrelia burgdorferi as the cause of Lyme disease, a new tick-borne infection occurring in the United States, almost identical spirochaetes have been isolated from the tick Ixodes ricinus in Europe. As a result, the spirochaetal aetiology of skin diseases, which had long been recognized as tick-borne infections, namely erythema chronicum migrans with its neurological complications of the tick-borne meningopolyneuritis of Garin-Bujadoux-Bannwarth, acrodermatitis chronica atrophicans and lymphadenosis cutis benigna, could be confirmed by means of microbiological, histological and serological methods. On the basis of case histories it had already been assumed for some time that anetodermia maculosa and the localised sclerodermas might also be caused by a tick-borne agent. The results of serological investigations have now strengthened this assumption, although microbiological confirmation is still lacking.