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Fabry disease is an X-chromosomal recessive deficiency of the lysosomal hydrolase alpha-galactosidase A (alpha-Gal). This results in an accumulation of globotriaosylceramide (GL-3) in a variety of cells often with subsequent functional impairment. Here, the impact of Fabry disease on the biology of circulating angiogenic cells (CACs) and the endothelial response to transient ischemia was investigated. Untreated patients with Fabry disease (n = 26), patients after initiation of alpha-Gal enzyme replacement therapy (ERT) (n = 16) and healthy controls (n = 26) were investigated. Endothelial function was assessed by the EndoPAT2000 device. CAC numbers were assessed by flow-cytometry, CAC function by a modified Boyden chamber assay. Fabry patients showed a pathologic endothelial response, which normalized after ERT. CACs were increased in number, but functionally impaired. Immunofluorescence and electron microscopy identified an accumulation of GL-3 in Fabry CACs. ERT attenuated CAC dysfunction and improved markers of oxidative stress response in Fabry patients via a reduction in GL-3 accumulation in vitro and in vivo. Silencing of alpha-Gal in healthy CACs impaired their migratory capacity underlining a key role of this enzyme for CAC function. CAC supernatant as well as CACs from Fabry patients impaired angiogenesis and migratory capacity of HUVECs providing a mechanistic link between CAC and endothelial dysfunction. CAC adhesion to TNF-α pre-stimulated HUVECs and tube formation was impaired by alpha-Gal knockdown. Fabry patients show a dysfunction of CAC and a pathologic endothelial response. ERT improves CAC and endothelial function and thus may attenuate development of cardiovascular disease in the long term in this patient population.

Diabetes mellitus due to its high prevalence and associated complications is a major socioeconomic health problem. Diabetes is characterized by multiple macro- and microvascular complications (e.g. diabetic nephropathy, cardiomyopathy, neuropathy, retinopathy). Research efforts aim to elucidate pathophysiological mechanisms contributing to the disease process. MicroRNAs are endogenous small single stranded molecules regulating targets through mRNA cleavage or translational inhibition. MicroRNAs regulate many biological cellular functions and are often deregulated during diseases. The aim of the present article is to summarize the current knowledge of the impact of microRNAs on the development of diabetes and its associated complications including endothelial and vascular smooth muscle cell dysfunction, diabetic cardiomyopathy, diabetic nephropathy, regulation of pancreatic beta cell function as well as skeletal muscle and hepatic involvement.

Epigenetics represents a phenomenon of altered heritable phenotypic expression of genetic information occurring without changes in DNA sequence. Epigenetic modifications control embryonic development, differentiation and stem cell (re)programming. These modifications can be affected by exogenous stimuli (e.g., diabetic milieu, smoking) and oftentimes culminate in disease initiation. DNA methylation has been studied extensively and represents a well-understood epigenetic mechanism. During this process cytosine residues preceding a guanosine in the DNA sequence are methylated. CpG-islands are short-interspersed DNA sequences with clusters of CG sequences. The abnormal methylation of CpG islands in the promoter region of genes leads to a silencing of genetic information and finally to alteration of biological function. Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease. We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting.

The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17β- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94 ± 15.5% vs. 17.1 ± 3.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.

Because of the differences in the signals from recurrent tumours and fibrosis during MRT, this method is highly suitable for differentiating between recurrent gynaecological tumours and scar formation. The value of MRT in investigating suspected recurrences was studied in 27 patients aged between 34 and 83 years. It was possible to distinguish between recurrent tumour with its high intensity signal from low signal fibrosis, using T2-weighted spin echo sequences in all cases. By means of multiplanar reconstruction and because of its high soft tissue contrast it was possible to determine the extent of tumour growth and differentiate it from surrounding tissues. With a sensitivity of 90%, specificity of 100% and accuracy of 92%, MRT is superior to all other imaging methods, including CT, in the diagnosis of tumour recurrence.

We present an experimental and theoretical investigation of the phonon dispersion relations in zinc blende (3C) SiC. The experimental data were obtained for the entire Brillouin zone by inelastic x-ray scattering (IXS) using a synchrotron radiation source. Eigenvector analysis is performed with the aid of state-of-the-art linear response first principles calculations based on density functional theory. The theoretical predictions reproduce the experimental phonon dispersion remarkably well. These results are compared with data obtained previously for the 〈111〉 direction by Raman spectroscopy using several SiC polytypes and the backfolding technique. IXS data for 4H modification along the c axis are also reported.

Organ transplantation has evolved rapidly and there is now widespread use of donated organs for the treatment of end-stage organ failure. Although the therapeutic options achieving long-term graft survival have improved, acute and chronic rejections are still a major problem. Studies to identify noninvasive biomarkers for rejection and underlying molecular events have increased significantly in the past decade, but a major breakthrough is still missing. The recent discovery of small regulatory RNA molecules (microRNAs) resulted in a new and improved understanding of the mechanisms of gene regulation and also led to the development of the first new microRNA (miRNA)-based therapies. miRNAs are endogenous, single-stranded RNAs consisting of about 19–25 noncoding nucleotides, which have an important role in regulating gene expression. Additionally, circulating miRNAs that might be useful as novel disease biomarkers were detected. Here, we summarise current knowledge about the role of miRNAs in immunology and transplantation medicine and their role as potential biomarkers. We also focus on the molecular mechanisms and therapeutic implications of the use of miRNA-based therapeutic strategies to improve long-term allograft survival.

Background Therapeutic strategies aiming to reduce ischemia/reperfusion injury by conditioning tissue tolerance against ischemia appear attractive not only from a scientific perspective, but also in clinics. Although previous studies indicate that remote ischemic intermittent preconditioning (RIPC) is a systemic phenomenon, only a few studies have focused on the elucidation of its mechanisms of action especially in the clinical setting. Therefore, the aim of this study is to evaluate the acute microcirculatory effects of remote ischemic preconditioning on a distinct cutaneous location at the lower extremity which is typically used as a harvesting site for free flap reconstructive surgery in a human in-vivo setting. Methods Microcirculatory data of 27 healthy subjects (25 males, age 24 ± 4 years, BMI 23.3) were evaluated continuously at the anterolateral aspect of the left thigh during RIPC using combined Laser-Doppler and photospectrometry (Oxygen-to-see, Lea Medizintechnik, Germany). After baseline microcirculatory measurement, remote ischemia was induced using a tourniquet on the contralateral upper arm for three cycles of 5 min. Results After RIPC, tissue oxygen saturation and capillary blood flow increased up to 29% and 35% during the third reperfusion phase versus baseline measurement, respectively (both p = 0.001). Postcapillary venous filling pressure decreased statistically significant by 16% during second reperfusion phase (p = 0.028). Conclusion Remote intermittent ischemic preconditioning affects cutaneous tissue oxygen saturation, arterial capillary blood flow and postcapillary venous filling pressure at a remote cutaneous location of the lower extremity. To what extent remote preconditioning might ameliorate reperfusion injury in soft tissue trauma or free flap transplantation further clinical trials have to evaluate. Trial registration ClinicalTrials.gov: NCT01235286

In Achilles tendon injuries, it is suggested that a pathological continuum might be evident from the healthy Achilles tendon to Achilles tendinopathy to Achilles tendon rupture. As such, risk factors for both tendinopathy and rupture should be the same. Hereditary and medical risk factors for Achilles tendinopathy and Achilles tendon rupture are the same to a similar extent in a matched pair analysis. Matched pair study; level of evidence: 3. Recreational sportsmen as well as athletes on national level. 566 questionnaires were analysed. 310 subjects were allocated to 3 groups (A, B, C) after matching the pairs for age, weight, height and gender: (A) healthy Achilles tendons (n = 89, age 39 ± 11 years, BMI 25.1 ± 3.9, females 36%), (B) chronic Achilles tendinopathy (n = 161, age 41 ± 11 years, BMI 24.4 ± 3.7, females 34%), (C) acute Achilles tendon rupture (n = 60, age 40 ± 9 years, BMI 25.2 ± 3.2, females 27%). We found a positive family history of Achilles tendinopathy as a risk factor for Achilles tendinopathy (OR: 4.8, 95% CI: 1.1–21.4; p = 0.023), but not for Achilles tendon rupture (OR: 4.0, 95% CI 0.7–21.1, p = 0.118). Smoking and cardiac diseases had a lower incidence in Achilles tendinopathy than in healthy subjects (both p = 0.001), while cardiovascular medication did not change the risk profile. Identifying risk factors associated with Achilles tendon disorders has a high clinical relevance regarding the development and implementation of prevention strategies and programs. This cross-sectional study identified a positive family history as a significant solitary risk factor for Achilles tendinopathy, increasing the risk fivefold. However, in this matched pair analysis excluding age, weight, height and gender as risk factors no further factor necessarily increases the risk for either Achilles tendinopathy or Achilles tendon rupture.

BACKGROUND: Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. METHODS AND RESULTS: Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2-associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival. CONCLUSIONS: Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease. [KEYWORDS: Animals, Apoptosis/drug effects, Arterioles/pathology, Capillaries/pathology, Cell Hypoxia, Cells, Cultured/drug effects/metabolism, Collagen, Drug Combinations, Drug Evaluation, Preclinical, Endothelial Cells/ metabolism/pathology, GATA2 Transcription Factor/biosynthesis/genetics, Gene Expression Profiling, Heart Failure/etiology, Heme Oxygenase-1/biosynthesis/genetics, Laminin, Male, Mice, Mice, Inbred C57BL, MicroRNAs/antagonists & inhibitors/genetics/ physiology, Myocardial Infarc

Summary Background and objectives MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form. We tested whether circulating miRNAs in the plasma of critically ill patients with acute kidney injury (AKI) at the inception of renal replacement therapy are deregulated and may predict survival. Design, setting, participants, & measurements We profiled miRNAs using RNA isolated from the plasma of patients with AKI and healthy controls. The results were validated in 77 patients with acute kidney injury, 30 age-matched healthy controls, and 18 critically ill patients with acute myocardial infarction by quantitative real-time PCR. Results Circulating levels of miR-16 and miR-320 were downregulated in the plasma of kidney injury AKI patients, whereas miR-210 was upregulated compared with healthy controls (all P 0.0001) and disease controls (miR-210 and miR-16: P 0.0001; miR-320: P 0.03). Cox regression (P 0.05) and Kaplan–Meier curve analysis (P 0.03) revealed miR-210 as an independent and powerful predictor of 28-day survival. Conclusions Circulating miRNAs are altered in patients with kidney injury AKI. MiR-210 predicts mortality in this patient cohort and may serve as a novel biomarker AKI reflecting pathophysiological changes on a cellular level. Clin J Am Soc Nephrol 6: 1540–1546, 2011. doi: 10.2215/CJN.00430111

Background. Due to the shortage of deceased donors ABO-incompatible (ABOi) living kidney transplantation has become a popular alternative to deceased kidney transplantation. In recent years, recipient desensitization with a combination of anti-CD20 treatment (rituximab), antigen-specific immunoadsorptions (IA) and intravenous immunoglobulin (IVIG), led to promising short-term and intermediate-term results. However, little is known about the impact of this intensified desensitization protocol on the risk of surgical and infectious complications. Methods. We retrospectively analysed 21 consecutive recipients who underwent ABOi renal transplantation. Pre-transplant desensitization included administration of rituximab (375 mg/m 2 ), mycophenolate mofetil (MMF), tacrolimus and prednisolone 4 weeks prior of scheduled transplantation as well as IA and IVIG. Forty-seven patients who underwent ABO-compatible (ABOc) renal transplantation served as the control group. Medical records and electronic databases were reviewed for patient and graft survival, renal function, rate of rejections, viral and bacterial infections as well as for surgical complications (SCs) post-transplantation. Results. All patients showed an immediate graft function. During a mean follow-up of 15.7 6 8.3 months (interquartile range 11.9) patient survival was 95 and 98% in the ABOi and ABOc group, respectively. Allograft survival and function, as assessed by serum creatinine levels and calculated glomerular filtration rate at 1 year, did not differ between ABOi and ABOc recipients. Furthermore, the rate of biopsyproven acute rejections was comparable between the two groups. However, there was a trend towards more SCs within the ABOi group (29 versus 11%, non-significant). In addition, the rate of viral infections including cytomegalovirus, Herpes simplex virus, Varicella zoster virus and polyoma virus was significantly increased among the ABOi recipients (50 versus 21%; P ¼ 0.038) despite comparable tacrolimus trough levels and MMF and steroid doses. Conclusions. Our results, in line with the extended experience of other groups, demonstrate favourable short-term allograft survival and function after ABOi renal transplantation after desensitization with antigen-specific IA, IVIG and rituximab. However, the intensified desensitization was associated with an increased risk of infectious complications. This observation prompted us to briefly escalate the desensitization protocol in ABOi kidney recipients in our centre.

Commercially available bioethanol-fueled fireplaces have become increasingly popular additions for interior home decoration in Europe and more recently in the United States. These fireplaces are advertised as smokeless, ecologically friendly, and do not require professional installation, formal gas lines, or venting. Although manufacturers and businesses promote their safety, recent presentations of injuries have alerted the authors to the relevant danger bioethanol fireplaces can pose for the incautious user. Are bioethanol fireplaces going to become the future threat in domestic burn accidents beside common barbeque burns? A Medline literature search on barbeque and domestic fireplace accidents was performed to compare and stratify the injury patterns reported and to identify a risk profile for contemporary bioethanol-fueled fireplaces. To exemplify, two representative clinical cases of severe burn accidents caused by bioethanol-fueled fireplaces, both treated in the burn unit of the authors, are being presented. Design fireplaces are being recognized as an increasing source of fuel and fire-related danger in the home. This risk may be underestimated by the uninformed customer, resulting in severe burn injuries. Because bioethanol-fueled fireplaces have become more commonplace, they may overtake barbecue-related injury as the most common domestic burn injury.

Under physiological conditions, kidneys work continuously, 168 h/week. In contrast, patients with end-stage renal disease are usually dialysed only 12 h/week. Even if considered adequate by current Kt/V-based dose estimates, this unphysiological dose is associated with an unacceptable annual mortality rate of 10–20%. Increasing dialysis dose might ameliorate this mortality rate. Eleven patients were switched from their conventional haemodialysis (cHD, 3 × 4 h/week) to an intensified short daily home haemodialysis regimen (sdhHD, 6 × 3 h/week) and followed up for 12 months. Different parameters were evaluated before treatment conversion and quarterly during follow-up [i.e. dialysis efficacy, mean arterial pressure (MAP), antihypertensive drug score, haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight, albumin, protein), C-reactive protein, calcium–phosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy]. HD efficacy as assessed by cumulative blood volume increased after dialysis intensification (P

BackgroundOsteopontin is a pleiotropic cytokine involved in the recruitment and retention of neutrophils to sites of inflammation, which are the primary targets cells in antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). Osteopontin may play a role in the pathogenesis of AAV.Methods24 patients with systemic AAV and six patients with limited granulomatous disease were included. 19 patients were followed up at 6 and 12 months after the initiation of immunosuppressive therapy. 21 matched healthy volunteers and 20 body mass index and glomerular filtration rate-matched patients with IgA nephropathy were included as controls. Plasma levels of osteopontin were measured by ELISA. Disease activity was gauged by the Birmingham vasculitis activity score (BVAS) and C-reactive protein (CRP).ResultsOsteopontin levels are elevated compared with controls (healthy pConclusionsActive AAV is characterised by increased plasma levels of osteopontin, which decrease dramatically with successful therapy. Osteopontin may mediate the inflammatory process in AAV through the recruitment of neutrophils.

Background Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function. Methods We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort. Results In our patients EPCs were related only to age (r = 0.154; p = 0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p = 0.03) and patient age (p = 0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p = 0.02). Conclusions We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population.

Using X-rays of energies around the Ni 1s binding energy (8333 eV), we measured the fluorescence spectra of the valence electrons of a NiAl single crystal for different values of the momentum transfer q → . The shape of the obtained spectra shows a strong dependence on q → . This non-isotropic behaviour of fluorescence from valence electrons is explained by considering the absorption of the incident photon and the re-emission of the fluorescence photon as one single resonant inelastic scattering process, which includes a law of Bloch k → -vector conservation. By comparing our experimental results with calculations based on this point of view, we show its validity for hard X-rays.

Osteopontin is a pleiotropic cytokine that has been implicated as a key factor in the development of atherosclerosis, a major complication of hypertension. We have earlier shown that olmesartan reduces mediators of vascular inflammation in patients with hypertension and cardiovascular disease. We aimed at studying the effect of olmesartan and/or pravastatin on osteopontin plasma levels, and the association between vascular inflammation markers and osteopontin in hypertensive patients.We assessed a panel of vascular inflammation markers and osteopontin during 12 weeks of therapy with 20mg olmesartan (n=94) or placebo (n=96) in a prospective, double-blind, multi-center study in patients with essential hypertension (re-evaluation of the EUTOPIA trial blood samples). Pravastatin (20mg) was added to the double-blind therapy at week 6 in both arms. The association of demographic variables and inflammation markers with osteopontin has been analyzed as well.Baseline osteopontin plasma concentrations in the study population were elevated compared to healthy controls (32.85+/-19.04ng/mL vs. 23.82+/-3.69ng/mL, p=0.027). Mono-therapy with olmesartan and co-therapy with pravastatin reduced levels of circulating osteopontin (p0.001). The addition of pravastatin to the placebo treatment-arm resulted in a reduction of osteopontin levels as well (p0.01). osteopontin plasma levels correlated with VCAM-1 (r=0.27; p=0.0002), ICAM-1 (r=0.18; p=0.015), IL-6 (r=0.35; p0.0001) and hsCRP (r=0.22; p=0.0022).We show, for the first time, that olmesartan significantly decreases osteopontin concentrations. Co-therapy with pravastatin also reduces osteopontin levels. Elevated osteopontin levels in hypertensive patients correlate with adhesion molecules and inflammation markers.

The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. The normal kidneys eliminate approximately 60% of ampicillin (371.39 Da) and sulbactam (255.22 Da). Concomitant with the decline in renal function, the terminal elimination half-life increases from 1 up to 24 h in patients with ESRD. Patients on three times weekly low flux haemodialysis exhibit a half-life of 2.3 h on and 17.4 h off dialysis. In contrast, in the present observation the elimination half-life in a single patient with acute kidney injury undergoing extended daily dialysis (EDD) with a polysulphone membrane was 1.5 h, indicating that the current dosing regimen for haemodialysis outpatients (ampicillin/sulbactam 2.0/1.0 g/day) would result in a significant underdosing for patients undergoing EDD.

The iron structural and magnetic transition between the magnetic (bcc-$\ensuremath{\alpha})$ and the nonmagnetic (hcp-$\ensuremath{\epsilon})$ phases has been studied monitoring the pressure dependence of the Fe-$K\ensuremath{\beta}$ fluorescence line excited with monochromatic synchrotron radiation. The relative intensity of the two multiplets shows an S-shaped pressure curve with flex point at the known transition pressure of 130 kbar. The S width of $\ensuremath{\approx}30$ kbar also coincides with the one determined in structural determinations, and in magnetism studies using M\"ossbauer techniques. This shows how the x-ray emission method can be used to probe the local magnetic properties of atoms under extreme thermodynamic conditions.

International audience; The energy scale of a triple-axis x-ray spectrometer with meV energy resolution based on perfect silicon crystal optics is calibrated, utilizing the most recent determination of the silicon lattice parameter and its thermal expansion coefficient and recording the dispersion of longitudinal acoustic and optical phonons in a diamond single crystal and the molecular vibration mode in liquid nitrogen. Comparison of the x-ray results with previous inelastic neutron and Raman scattering results as well as with ab initio phonon dispersion calculations yields an overall agreement better than 2%.

In this work we discuss saturation performance of a fiber optic parametric amplifier. A simple numerical model is described and applied to specific cases. A system experiment using a saturated amplifier illustrates a 4 dB improvement in required signal to noise ratio for a fixed bit error ratio.

Input power dynamic range enhancement and amplitude regeneration of highly distorted signals are demonstrated experimentally for 40 Gbit/s RZ-DPSK in a single-pump fibre parametric amplifier with 22 dB smallsignal gain.

Fiber optical parametric amplifiers (FOPA's) are attractive components in future optical networks. Not only do they provide amplification, they also offer additional functionalities such as wavelength conversion, demultiplexing, and signal regeneration. The pump power in a FOPA is currently limited due to Brillouin scattering (BS). There are several ways to reduce the impact of BS, including phase modulation of the pump source and novel fiber types. In this paper we demonstrate the impact of BS on the gain of a FOPA.

Zusammenfassung: Erweiterte Suizide durch Schusswaffen sind häufig durch eine sorgfältige Fundortanalyse zu klären. Im dargestellten Fall wurde eine 38-jährige Frau in Rückenlage auf dem Bett im Schlafzimmer aufgefunden. Im Bereich der linken Brust fand sich eine rundliche Einschusswunde. Neben dem Bett wurde eine Schusswaffe gefunden. Im Wohnzimmer lag ein 40-jähriger Mann in Bauchlage auf der Erde in einer größeren Blutlache. Ein unvollendeter Abschiedsbrief fand sich auf dem Esstisch. Nach der äußeren Leichenschau am Fundort erfolgte eine Röntgenschichtuntersuchung. Hierdurch wurde bei der Frau ein absteigender Schusskanal von der linken Brust durch die Herzspitze dargestellt. Das Projektil konnte im Rippenzwischenraum nahe der Wirbelsäule lokalisiert werden. Bei dem Mann wurden ein Schusskanal durch den harten Gaumen und ein Projektil in der Schädelhöhle festgestellt; dieses lag nicht in einer Linie mit dem Schusskanal, sodass ein "Ringelschuss" diagnostiziert wurde. Die nachfolgende Sektion beider Leichen bestätigte die Befunde. Die bei der Autopsie sichergestellten Projektile konnten durch ballistische Untersuchungen der am Ereignisort sichergestellten Waffe zugeordnet werden

We have studied structural properties of the high pressure phases of molecular nitrogen at room temperature using synchrotron radiation and angle dispersive powder diffraction with image plates as detectors. The cubic δ-phase was found to be stable between 5 and 11 GPa. At 11 GPa a phase transition to a new tetragonal phase was observed. Structural refinements suggest, that the transition is due to an orientational ordering of the disklike disordered molecules of the δ-phase. At 16. 5 GPa the transition to the rhombohedral e-phase occurred.

High-energy X-ray focusing with bent-crystal monochromators is known to be hampered by so-called depth or crystal-thickness aberrations. A theoretical model of focus broadening based on the geometrical theory of X-ray diffraction in slightly deformed crystals is presented and compared with experimental data. First, it is shown that depth broadening can be avoided in the Laue geometry by an appropriate choice of asymmetry angle. Based on this finding, a monochromator for high-pressure diffraction experiments has been designed and a source-size-limited focal spot below 10 microns is observed. As a consequence of the box-shaped rocking curve of bent Laue crystals, the focus is free of long-ranging tails. Diffraction patterns of standard powder samples were recorded on imaging plates and a theoretical description of the energy-dispersion-related peak broadening is given. Finally, diffraction patterns of N2 at 180 kbar demonstrate the excellent data quality achievable with this monochromator.

To examine the clinical relevance of multislice CT (MSCT) scans in postoperative checks of the spine after osteosynthesis.The results of x-rays (apical lateral) in 30 patients having spinal surgery involving osteosynthesis (5 x metastasis, 20 x fractures, 3 x spondylolisthesis, 2 x scoliosis) were correlated to those of MSCT (140 kV, 200 mAs, collimation 4 x 1 mm, pitch 0.75; VolumeZoom, Siemens, Erlangen, Germany) with multiplanar reconstruction. Two radiologists independently checked the conventional x-ray and multislice CT scans for anatomical positioning, damage of osteosynthetic material, and intraspinal dislocation of bone fragments.By correlating conventional spinal x-rays with MSCT, additional diagnostic information was gained. In 9 of 30 patients MSCT revealed the extraosseal location of a screw tip (x-ray, 5/30), in 8/30 patients a narrowing of the spinal canal by osteosynthetic material was detected in MSCT (x-ray, 4/30), in 2/30 patients osteal fragments were detected in the vertebral canal by MSCT (x-ray, 0/30). In MSCT and in conventional x-ray a fracture of the osteosynthesis was correctly diagnosed in 3 patients. One patient underwent corrective surgery for dislocated osteosynthetic material, which was solely diagnosed with MSCT.Due to the high degree of additional diagnostic information MSCT seems to be the method of choice for postoperative spinal surgery involving osteosynthesis.

To optimize multislice computed tomography (MSCT) protocols of the midface for dose reduction and adequate image quality.MSCT (Somatom Volume Zoom, Siemens) of the midface was performed on 3 cadavers within 24 hours of death with successive reduction of the tube current, applying 150, 100, 70 and 30 mAs at 120 kV as well as 40 and 21 mAs at 80 kV. At 120 kV, a pitch of 0.875 and collimation of 4x1 mm were used, and at 80 kV, a pitch of 0.7 and collimation of 2x0.5 mm. Images were reconstructed in transverse and coronal orientation. Qualitative image analysis was separately performed by two radiologists using a five-point scale (1 = excellent; 5 = poor) applying the following parameters: image quality, demarcation and sharpness of lamellar bone, overall image quality, and image noise (1 = minor; 5 = strong). The effective body dose [mSv] and organ dose [mSv] of the ocular lens (using the dosimetry system "WINdose") were calculated, and the interobserver agreement (kappa coefficient) was determined.For the evaluation of the lamellar bone, adequate sharpness, demarcation and image quality was demonstrated at 120 kV/30 mAs, and for the overall image quality and noise, 120 kV/40 mAs was acceptable. With regard to image quality, the effective body dose could be reduced from 1.89 mSv to 0.34 mSv and the organ dose of the ocular lens from 27.2 mSv to 4.8 mSv. Interobserver agreement was moderate (kappa = 0.39).Adequate image quality was achieved for MSCT protocols of the midface with 30 mAs at 120 kV, resulting in a dose reduction of 70 % in comparison to standard protocols.

To evaluate the image quality of thin-section MSCT examinations of low-contrast objects such as liver lesions, and to find out whether a thin slice technique requires an increase in radiation dose.MSCT examinations of the liver were performed in the portal venous phase on a Volume Zoom Scanner (Siemens, Erlangen) with a collimation of 4 x 2.5 mm, 120 kV, 125 mAs and table speed of 12.5 mm. Forty small hypodense liver lesions with a mean size of 3 mm (1 to 8 mm) were reconstructed using a slice thickness of 3, 5, 7, and 10 mm. All lesions were evaluated for each slice thickness by 3 independent radiologists using a 5-point scale (excellent to poor) for the following 7 criteria: contrast, demarcation and contour of the lesion, image noise and quality, demarcation of liver veins and liver contour. The mean values of the reviewers' scores were calculated. The correlation of the three observers in the evaluation of the criteria was determined using the Kendall's Tau coefficient.The 3-mm thin sections were excellent in the evaluation of lesion detection, lesion contrast and lesion contour with a mean score of 1.4 compared to 4.1 for 10-mm sections. Concerning the criteria image quality and liver contour, thin sections achieved the best results in our series. Image noise was pronounced in thin sections but did not affect negatively the image analysis. Interrater agreement was 0.53 for the criterium image noise.Thin sections in MSCT examinations of low contrast objects such as liver lesions do not require an increase in radiation dose because the increase in image noise is compensated by improved lesion contrast.

To compare the radiation dose of whole-body multislice CT (MSCT) and conventional radiography with organ-specific CT in polytrauma.The whole-body MSCT encompassing brain, neck and midface, chest, abdomen and pelvis was performed on a Somatom Volume Zoom (Siemens). Conventional radiography consisted of chest and cervical, thoracic and lumbar spine in two views as well as pelvis (Polymat, Siemens). Three combinations of organ specific CT were chosen: CT examination of (1) head and cervical spine, (2) head, cervical spine and chest, (3) head, cervical spine and abdomen. The effective doses of whole-body MSCT and conventional radiography with organ-specific CT were calculated.Effective doses were 20 mSv for whole-body MSCT, 2 mSv for conventional x-ray, and 5 mSv for combination (1), 8 mSv for combination (2) and (3) 16 mSv for combination (3) of the organ-specific CT. The ratio of radiation dose between whole-body MSCT and radiography was 10 : 1. This ratio was reduced to 3 : 1, 2 : 1 and 1 : 1 when a combination of radiography and CT was performed.Whole-body MSCT in polytrauma compared to conventional radiography with organ-specific CT induces a threefold increased dose in unfavorable situations and no increased dose in favorable situations. Nevertheless, routine use of whole-body MSCT should be critically evaluated and should be adapted to the clinical benefit.

Very high-resolution inelastic x-ray scattering is employed to determine the dynamic response of the high-density crystalline water phases ice IX and ice XII in the Q=2.0-15.5 nm - 1 momentum transfer range. The spectra in the first and second Brillouin zone of the crystalline samples possess distinctive (Q,ω) dependencies. In particular, the response of ice IX gives evidence of the presence of an ensemble of excitations already at lowest Q. Similar features are found in the high-density amorphous water phase (HDA). The acoustic mode in HDA is well defined and little damped up to Q = 9 nm - 1 . Its slope is close to that of ice IX. Despite the apparent structural disorder of HDA its dynamic response appears crystal-like with a close resemblance to ice IX pointing at an intriguing high degree of short-range order.

In this paper we present the observation of acoustic modes in the spectra of molten NaCl measured over a large momentum transfer range using synchrotron radiation. A surprisingly large positive dispersion was deduced witha mode velocity exceeding the adiabatic value by nearly 70%. The large effect seems to be describable as a viscoelastic reaction of the liquid. Additionally, the derived dispersion resembles the Q-ω relation of the acoustic modes in liquid sodium. As an explanation for the large positive dispersion we propose that the density fluctuations in molten NaCI can be interpreted as a decoupled motion of the lighter and smaller cations on a nearly resting anionic background. These molten alkali halide measurements are the first experimental evidences for the so-called fast sound in a binary ionic liquid.

To optimize the examination protocols of multislice CT (MSCT) of the pelvis for dose reduction with regard to image quality.MSCT of the pelvis was performed on 5 cadaver specimens with stepwise reduction of the tube current at 140 kV (250, 200, 150, 100, 75, 50, 35, 25 mAs) and 120 kV (50, 27 mAs). The remaining scan parameters like collimation (4 x 1 mm) and table speed of 4 mm per rotation remained unchanged. Axial sections and coronal reconstructions were used to evaluate cortex, trabecular structures, subjective image quality, image noise and detail detectability (pelvis and SI joint), with evaluation performed independently by four blinded experienced radiologists on a 5-point scale. Kappa coefficient, accuracy of the observers to sort the films with regard to dose reduction and mean scores of image evaluation were determined for statistical analysis.The deterioration of the image quality was most pronounced for all criteria between 75 mAs and 50 mAs at 140 kV. Good results with adequate image quality were obtained for detail detectability at 50 mAs and 140 kV (effective dose [E]: 3.3 mSv) and for the remaining four criteria at 75 mAs (E: 4.9 mSv). There was a moderate agreement between the four observers (kappa coefficient: 0.27). All observers were excellent in arranging the images according to the increasing dose reduction.Image quality of MSCT of the pelvis appears to be acceptable at 75 mAs and 140 kV with the dose reduced to 46% of the average value of the nation-wide survey of the German Roentgen Society in 1999 for this type of examination.

The phonon dynamics in hydrogenated stretched polyethylene was investigated using inelastic x-ray scattering. The dispersion curve of longitudinal acoustic modes describing intrachain collective motions was measured in the first Brillouin zone, and compared to inelastic neutron scattering data on deuterated similar samples. This first exploration of the collective dynamics within the first Brillouin zone reveals the presence of an additional low energy component. In spite of its large energy distribution, this feature is seen to slightly disperse with momentum transfer Q. The possible origins of this low energy scattering are discussed; arguments converge towards the collective dynamics of the amorphous regions.

To compare image quality in magnetic resonance cholangiopancreatography (MRCP) performed with and without oral application of Lösferron (ferrous gluconate, Lilly Pharma, Hamburg).A prospective study compares MRCPs performed on 52 patients with a 1.5 T clinical whole body scanner using a standard body coil. After randomization, patients ingested either 0.5 l of Lösferron (n = 27, group 1) or no oral contrast agent (n = 25, group 2) prior to the examination. 7 RARE (40 to 20 degrees) sequences were obtained, followed by selected 3 mm HASTE (T 2 -weighted with fat suppression) sequences. After blinding, image quality was rated by two radiologists using a scale of 1 (not discernible) to 5 (very well discernible). The following sections of the biliary ductal system were evaluated: left and right hepatic duct, extrahepatic bile duct and intrapancreatic bile duct. The pancreatic duct was evaluated by its location: head, body and tail of the pancreas. A Wilcoxon-Mann-Whitney test was used to determine significant differences (p0.05) between sampled ductal segments. Correction for multiple testing was applied.The oral application of Lösferron was well tolerated by all patients, and all sequences could be acquired and evaluated in all 52 patients. For the different sections of the biliary system, the mean ratings with and without Lösferron were, respectively, 3.28 and 3.36 for the left hepatic duct, 3.26 and 3.33 for the right hepatic duct, 3.46 and 4.0 for the extrahepatic bile duct, and 2.8 and 3.48 for the intrapancreatic bile duct. The corresponding ratings for the pancreatic duct were 2.8 and 3.24 for the pancreatic head, 2.84 and 3.38 for the pancreatic body, and 2.68 and 3.22 for the pancreatic tail. The differences with and without contrast agent were not statistically significant. Interobserver variability was between 0.37 for the pancreatic duct in the tail of the pancreas and 0.66 for the right hepatic duct.Despite the trend toward a better rating of the image quality for all sections of the pancreaticobiliary ductal system with Lösferron, a significant difference was not found in any ductal section after correction for multiple testing. Thus, we believe that the ingestion of Lösferron is not absolutely required prior MRCP.

Despite the importance of water in natural science andits unique role in defining biological activity, the structuraland dynamical properties of liquid water are far from beingcompletely understood. Numerous experimental and theo-retical studies [1,2] have already been devoted to under-standing the distinctive properties of water and, inparticular, the role of the intermolecular hydrogen bonds.There is a common agreement that the unique physico-chemical behavior of water arises from the hydrogen-bondorganization of water molecules, which is characterized byan open three-dimensional hydrogen-bond network with analmost perfect tetrahedral arrangement of nearest neigh-bors. Three models are currently proposed to explain theproperties and anomalies of water: (i) the existence of aliquid-liquid transition line between two liquid phases ofdifferent densities [3,4], (ii) a singularity-free scenario inwhich the thermodynamic anomalies are related to thepresence of low-density and low-entropy structural hetero-geneities [5], and (iii) a description within the frameworkof mode-coupling theory, initially developed to describethe properties of glass-forming liquids [6]. It remains,however, a challenge to find discriminating experimentaltests. Most of the work on water has been focused on thechanges of its properties with temperature, but to a lesserextent on its properties under pressure. Early pressurestudies dealt with the evolution of thermodynamic andtransport properties such as density, heat capacity, com-pressibility, longitudinal relaxation time, diffusion coeffi-cient, and zero-frequency sound velocity [2,7–9]. Morerecent pressure work focused on the microscopic structuralchanges of the liquid water structure: neutron and x-rayscattering experiments were performed to pressures of 1.6[10–12] and 0.8 GPa [13], respectively.Previous inelastic x-ray and neutron scattering (IXS andINS) work focused to a large extent on the temperatureevolution of the high-frequency dynamics at ambient pres-sure [14–18]. These experiments revealed a particularlylarge dispersion effect in the sound velocity as a function offrequency, which—at variance with many other liquids[19]—takes place at very high frequencies, i.e., in theterahertz region. Specifically, at