An ultra-high vacuum scanning tunneling microscope operating at sub-Kelvin temperatures and high magnetic fields for spin-resolved measurements.

We present the construction and performance of an ultra-low-temperature scanning tunneling microscope (STM), working in ultra-high vacuum (UHV) conditions and in high magnetic fields up to 9 T. The cryogenic environment of the STM is generated by a single-shot 3He magnet cryostat in combination with a 4He dewar system. At a base temperature (300 mK), the cryostat has an operation time of approximately 80 h. The special design of the microscope allows the transfer of the STM head from the cryostat to a UHV chamber system, where samples and STM tips can be easily exchanged. The UHV chambers are equipped with specific surface science treatment tools for the functionalization of samples and tips, including high-temperature treatments and thin film deposition. This, in particular, enables spin-resolved tunneling measurements. We present test measurements using well-known samples and tips based on superconductors and metallic materials such as LiFeAs, Nb, Fe, and W. The measurements demonstrate the outstanding performance of the STM with high spatial and energy resolution as well as the spin-resolved capability.

Impact of Single Center Treatment on Ewing Sarcoma 10-Year Long Term Survival Rates.

PURPOSE OF THE STUDY Ewing sarcomas (ES) are the second most common solid malignant bone tumors in both, children and adolescents, and systemic chemotherapy protocols were established during the last 3 decades which proved to be a successful approach in addition to local treatment. The purpose of the present study is (i) to provide survival rates and prognostic factors for patients with ES which received treatment in a single center and (ii) to compare data with results of multicenter studies. MATERIALS AND METHODS Patients (n = 38) were treated by the same surgeon whereas surgery was combined with radiotherapy in 55.3% of the patients (n = 21). Median age at diagnosis was 17.5 years (4.7-60) and the median follow-up time for all patients was 8.2 years (9.8 years for survivors, 3.2 years for non-survivors). RESULTS The survival rate for metastasis free sarcoma decreases from 90.5% to 50% for patients diagnosed with disseminated disease stage. Patients with a good response to chemotherapy survived in 83.3% of the cases. In addition, a higher OS was found for patients younger than 15 years (82.4%) when compared to patients older than 15 years (73.3%). In contrast, multicenter studies reported lower survival rates for metastasis free (~60%) and metastasis stages (< 40%). DISCUSSION The survival rates in the present single center study are higher than the rates reported from multi-center studies although same chemotherapy protocols were used and no substantially difference are apparent for patient population. CONCLUSIONS Based on the present data we re-emphasize that patients with Ewing sarcoma receive appropriate treatment in a large and qualified center particularly considering the survival rates. In addition, our data underline that a close collaboration between the oncological team and the experienced surgeon is crucial for patient's care. Key words: Ewing sarcoma, survival rate, single center, prognostic factors, chemotherapy, surgery, multi center, single center.

Study of water adsorption and capillary bridge formation for SiO(2) nanoparticle layers by means of a combined in situ FT-IR reflection spectroscopy and QCM-D set-up.

Water adsorption and capillary bridge formation within a layer of SiO2-nanoparticles were studied in situ by means of a combination of quartz crystal microbalance (QCM-D) with dissipation analysis and Fourier transformation infrared reflection absorption spectroscopy (FT-IRRAS). FT-IR data were employed to distinguish the "ice-like" and "liquid-like" contributions and to support the analysis of the QCM-D data concerning mass change and dissipation. Combined measurements show that for SiO2-nanoparticles with a diameter of about 250 nm, the formation of two adsorbed monolayers of water as well as bulk water leads to a rather linear increase in the dissipation for relative humidity values of up to 60% which is followed by a strong increase in dissipation during the actual liquid bridge formation. Subsequently, the dissipation drops again when the relative humidity is further increased to values >90%.

The impact of T-cell depletion techniques on the outcome after haploidentical hematopoietic SCT.

Several T-cell depletion (TCD) techniques are used for haploidentical hematopoietic SCT (HSCT), but direct comparisons are rare. We therefore studied the effect of in vitro TCD with graft engineering (CD34 selection or CD3/CD19 depletion, 74%) or in vivo TCD using alemtuzumab (26%) on outcome, immune reconstitution and infections after haploidentical HSCT. We performed a retrospective multicenter analysis of 72 haploidentical HSCT in Switzerland. Sixty-seven patients (93%) had neutrophil engraftment. The 1-year OS, TRM and relapse incidence were 48 (36-60)%, 20 (11-33)% and 42 (31-57)%, respectively, without differences among the TCD groups. In vivo TCD caused more profound lymphocyte suppression early after HSCT, whereas immune recovery beyond the second month was comparable between the two groups. Despite anti-infective prophylaxis, most patients experienced post-transplant infectious complications (94%). Patients with in vivo TCD had a higher incidence of CMV reactivations (54% vs 28%, P=0.015), but this did not result in a higher TRM. In conclusion, TCD by graft engineering or alemtuzumab are equally effective for haploidentical HSCT.

Management of children and adolescents with primary immune thrombocytopenia: controversies and solutions.

The management including diagnostic procedures, prophylaxis, treatment and follow-up of patients with primary immune thrombocytopenia (ITP) in childhood is controversial due to limited clinical data, difficulties in the estimation of individual bleeding risk and heterogeneity of pathophysiology potentially causing various treatment responses. Advances in the management of children include increased international collaborations, improved quality of diagnosis and treatment, increased clinical data, refinement of consensus statements where clinical evidence is absent, new drugs and last but not least establishment of watch-and-wait strategies. The Intercontinental Cooperative ITP Study Group promotes international collaboration since more than 10 years based on a worldwide network and experience in registries. Future considerations include concentration of available resources, strengthening international collaboration, focusing on most important scientific and clinical questions, such as identification of the subgroup of patients that benefits most from prophylactic platelet-enhancing treatments and investigation of treatment endpoints other than concepts solely based on the platelet count, including bleeding symptoms, health-related quality of life and economical aspects of treatments.

Hereditary angioedema (HAE) in children and adolescents--a consensus on therapeutic strategies.

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.

[Consensus recommendations of the German Radiology Society (DRG), the German Cardiac Society (DGK) and the German Society for Pediatric Cardiology (DGPK) on the use of cardiac imaging with computed tomography and magnetic resonance imaging]. / Konsensusempfehlungen der DRG/DGK/DGPK zum Einsatz der Herzbildgebung mit Computertomografie und Magnetresonanztomografie.

Cardiac magnetic resonance imaging (MRI) and computed tomography (CT) have been developed rapidly in the last decade. Technical improvements and broad availability of modern CT and MRI scanners have led to an increasing and regular use of both diagnostic methods in clinical routine. Therefore, this German consensus document has been developed in collaboration by the German Cardiac Society, German Radiology Society, and the German Society for Pediatric Cardiology. It is not oriented on modalities and methods, but rather on disease entities. This consensus document deals with coronary artery disease, cardiomyopathies, arrhythmias, valvular diseases, pericardial diseases and structural changes, as well as with congenital heart defects. For different clinical scenarios both imaging modalities CT and MRI are compared and evaluated in the specific context.

Caval flow reflects Fontan hemodynamics: quantification by magnetic resonance imaging.

INTRODUCTION: Failing Fontan circulation is a multifactorial problem without clear predictors and with uncertain onset. We sought to investigate the correlations between systemic venous flow return and the clinical condition of Fontan patients. METHODS: Flow measurements using phase contrast magnetic resonance imaging (MRI) were performed in the superior and inferior vena cava (SVC, IVC) in 61 Fontan patients. Median postoperative follow-up time was 6.7 (0.6-14.1) years; median age at MRI was 11.6 (4.0-44.6) years. Eight patients were identified clinically as a subgroup with suboptimal hemodynamics. The effective forward flow of combined SVC and IVC flow volume was defined as the venous cardiac index (vCI, l/min/m(2)). SVC flow ratio was defined as SVC flow in relation to vCI. The vCI and flow distribution between the SVC and IVC were investigated in relation to the hemodynamics and patients' age at MRI. RESULTS: Venous flow return through the SVC was 1.1 (0.6-3.4) l/min/m(2) and through the IVC 1.8 (0.6-3.2) l/min/m(2); total vCI was 3 l/min/m(2) (1.2-5.1). Patients with suboptimal Fontan hemodynamics showed significantly lower IVC flow return (median of 1.5 vs. 1.9 l/min/m(2), p = 0.027) and increased SVC flow ratio (0.56 vs. 0.35, p = 0.005) in comparison to those with good clinical condition. The total vCI decrease was correlated with older patient age (r = 0.575, p < 0.001). CONCLUSIONS: Altered systemic venous flow return is associated with suboptimal Fontan hemodynamics and seems to progress with patients' age and long-term follow-up after Fontan operation. Thus, MRI flow volume measurements might help in monitoring Fontan patients before the onset of clinical signs of suboptimal hemodynamics.

First-principles study of nitrogen doping in cubic and amorphous Ge2Sb2Te5.

We investigated the structural, electronic and vibrational properties of amorphous and cubic Ge(2)Sb(2)Te(5) doped with N at 4.2 at.% by means of large scale ab initio simulations. Nitrogen can be incorporated in molecular form in both the crystalline and amorphous phases at a moderate energy cost. In contrast, insertion of N in the atomic form is very energetically costly in the crystalline phase, though it is still possible in the amorphous phase. These results support the suggestion that N segregates at the grain boundaries during the crystallization of the amorphous phase, resulting in a reduction in size of the crystalline grains and an increased crystallization temperature.

The influence of tumor- and treatment-related factors on the development of local recurrence in osteosarcoma after adequate surgery. An analysis of 1355 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

BACKGROUND: Local recurrence (LR) in osteosarcoma is associated with very poor prognosis. We sought to evaluate which factors correlate with LR in patients who achieved complete surgical remission with adequate margins. PATIENTS AND METHODS: We analyzed 1355 patients with previously untreated high-grade central osteosarcoma of the extremities, the shoulder and the pelvis registered in neoadjuvant Cooperative Osteosarcoma Study Group trials between 1986 and 2005. Seventy-six patients developed LR. RESULTS: Median follow-up was 5.56 years. No participation in a study, pelvic tumor site, limb-sparing surgery, soft tissue infiltration beyond the periosteum, poor response to neoadjuvant chemotherapy, failure to complete the planned chemotherapy protocol and biopsy at a center other than the one performing the tumor resection were significantly associated with a higher LR rate. No differences were found for varying surgical margin widths. Surgical treatment at centers with small patient volume and additional surgery in the primary tumor area, other than biopsy and tumor resection, were significantly associated with a higher rate of ablative surgery. CONCLUSIONS: Patient enrollment in clinical trials and performing the biopsy at experienced institutions capable of undertaking the tumor resection without compromising the oncological and functional outcome should be pursued in the future.

Intravenous immunoglobulins induce potentially synergistic immunomodulations in autoimmune disorders.

The increase in platelets in patients with immune thrombocytopenia (ITP) by intravenous administration of human immunoglobulin concentrates (IVIG) reflects a therapeutic immunomodulatory intervention targeted at the disturbed immune response in many inflammatory and autoimmune disorders. These immunoglobulin concentrates contain large numbers of antibodies as well as trace levels of various other immunologically active molecules. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T- and B- lymphocyte effects, macrophage effects, mediated by distinct Fc-gamma receptors. In addition, effects on complement components and apoptosis have also been observed. Synergism between the different elements of the immune response characterizes the beneficial effects of IVIG in inflammatory and autoimmune disorders. They have immunopathogeneses and clinical manifestations which are difficult to define and therefore IVIG treatment indications remain heterogeneous. Dose finding studies are missing for most of the indications of the drug. In future research, defining the appropriate subgroups of patients should be undertaken. This may be accomplished by prospective registries collecting data on large numbers of patients with long-term follow-up. Controlled clinical and laboratory studies may follow based on new, validated patient selection criteria and focused on mechanisms of action, leading to more evidence-based indications.

Unravelling the mechanism of pressure induced amorphization of phase change materials.

Based on ab initio molecular dynamics simulations, we identify the atomistic mechanism of the pressure induced amorphization of Ge(2)Sb(2)Te(5). The simulations reveal that homopolar Ge/Sb bonds appear in cubic Ge(2)Sb(2)Te(5) under pressure, giving rise to square rings rotated by 45 degrees with respect to the crystalline axis whose formation is induced by the displacement of Te atoms filling the voids of neighboring Ge/Sb stoichiometric vacancies. The concentration of these topological defects increases with pressure up to 21 GPa at which the system is destabilized and transforms into an amorphous phase in agreement with experiments.

First-principles study of crystalline and amorphous Ge(2)Sb(2)Te(5) and the effects of stoichiometric defects.

Based on ab initio molecular dynamics simulations, we investigated the structural, electronic and vibrational properties of cubic and amorphous Ge(2)Sb(2)Te(5) (GST) phase change material, focusing in particular on the effects of defects in stoichiometry on the electronic properties. It turned out Ge/Sb deficiencies (excess) in the cubic phase induce a shift of the Fermi level inside the valence (conduction) bands. In contrast, the amorphous network is flexible enough to accommodate defects in stoichiometry, keeping the Fermi level pinned at the center of the bandgap (at zero temperature). Changes in the structural and electronic properties induced by the use of hybrid functionals (HSE03, PBE0) instead of gradient corrected functionals (PBE) are addressed as well. Analysis of vibrational spectra and Debye-Waller factors of cubic and amorphous GST is also presented.

Ecotoxicological characterization of hazardous wastes.

In Europe hazardous wastes are classified by 14 criteria including ecotoxicity (H 14). Standardized methods originally developed for chemical and soil testing were adapted for the ecotoxicological characterization of wastes including leachate and solid phase tests. A consensus on which tests should be recommended as mandatory is still missing. Up to now, only a guidance on how to proceed with the preparation of waste materials has been standardized by CEN as EN 14735. In this study, tests including higher plants, earthworms, collembolans, microorganisms, duckweed and luminescent bacteria were selected to characterize the ecotoxicological potential of a boiler slag, a dried sewage sludge, a thin sludge and a waste petrol. In general, the instructions given in EN 14735 were suitable for all wastes used. The evaluation of the different test systems by determining the LC/EC(50) or NOEC-values revealed that the collembolan reproduction and the duckweed frond numbers were the most sensitive endpoints. For a final classification and ranking of wastes the Toxicity Classification System (TCS) using EC/LC(50) values seems to be appropriate.

Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS).

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.

Characterisation of epitopes on barley mild mosaic virus coat protein recognised by a panel of novel monoclonal antibodies.

Barley mild mosaic virus (BaMMV), a member of the family Potyviridae, genus Bymovirus, is involved in the economically important yellow mosaic disease of winter barley in East Asia and Europe. We investigated serological properties of bacterially expressed BaMMV coat protein (CP) of a German isolate. Ten mouse monoclonal antibodies were produced using purified E. coli expressed BaMMV-CP as immunogen. The reactivity of MAbs with different strains of BaMMV was analysed by several immunological methods that are frequently used in diagnostic virology: enzyme-linked immunosorbent assay (ELISA), dot-blot, Western-blotting (WB), direct tissue blotting immunoassay (DTBIA) and immunoelectron microscopy (IEM). The amino acids involved in the formation of epitopes recognised by several MAbs were mapped by using synthetic pin-bound peptides and the localisation of epitopes in assembled virus particles was determined by electron microscope studies. MAbs V29 and M1 decorated the whole virion indicating that their epitopes 6PDPI9 and 96ITDDEK101, respectively, are exposed on the surface. The MAbs V6 and V14 both interacted with 44LPEPKM49, which seems to be accessible at only one end of the virus particle. The MAbs V6, V14, V29 and M1 detected epitopes common to a wide range of BaMMV isolates and can therefore be used effectively in routine diagnostic tests for BaMMV from barley leaves. We suggest that MAbs M1, V6, V14 and V29 are most suitable for use in TAS-ELISA, V6, V14 and V29 for Western blotting and V29 and M1 for electron microscope serology.

Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation.

This pilot study tested feasibility of natural killer cell purification and infusion (NK-DLI) in patients after haploidentical hematopoietic stem cell transplantation (HSCT). The aim was to obtain >or=1.0 x 10(7)/kg CD56+/CD3- NK cells and <1.0 x 10(5)/kg CD3+ T cells. Mononuclear cells were collected by 10 l leukapheresis. A two-step ex vivo procedure was used to purify NK cells, using an immunomagnetic T-cell depletion, followed by NK-cell enrichment. Five patients with high-risk myeloid malignancies were included, presenting 3-12 months after a haploidentical HSCT with mixed chimerism (3), impending graft failure (1) or early relapse (1). The purified product contained a median of 1.61 x 10(7)/kg (range 0.21-2.2) NK cells and 0.29 x 10(5)/kg (0.11-1.1) T cells. A purity of NK cells of 97% (78-99), a recovery of 35.5% (13-75), and a T-cell depletion of 3.55 log (2.9-4.5) was achieved. Infusions were well tolerated and none of the patients developed graft-versus-host disease. We observed an increase in donor chimerism in 2/5, stable mixed chimerism, decreasing chimerism and relapse of AML in one patient each. Selection of NK-DLI is technically feasible. NK cells are well tolerated when used as adoptive immunotherapy in recipients of haploidentical HSCT.

[MRI in postoperative assessment of univentricular heart disease: correlation with echocardiography and angiography]. / MRT in der postoperativen Diagnostik bei funktionell univentrikulärem Herz: Korrelation zu Echokardiographie und Kardangiographie.

PURPOSE: To determine the value of MRI in the postoperative evaluation of a singular ventricle compared to echocardiography and cardiac catheterization. MATERIALS AND METHODS: Thirty-one patients (range: 6 months to 30 years) with a functional single ventricle following palliative corrective operations. Five patients had a Blalock-Taussig-Shunt, 8 patients a Glenn-Anastomosis and 18 a cavopulmonary shunt (6 with classic Fontan-Circulation, 12 with modified cavopulmonary anastomosis). The results in terms of postoperative morphologic changes were compared to percutaneous echocardiography (31/31) and cardiac catheterization (6/31). RESULTS: Echocardiography, which was performed on all patients, could not visualize the entire length of the tunnel, the Glenn-Anastomosis or the central pulmonary arteries in 70 % of the patients due to an inadequate acoustic window. MRI was able to show the entire tunnel in 11/12 patients and the central pulmonary arteries in 30/31 patients. The exact anatomy was seen in all 6 patients undergoing cardiac catheterization. CONCLUSION: MRI is useful in the postoperative evaluation of a functionally single ventricle. It is superior to echocardiography. Cardiac catheterization should be reserved for patients with inconclusive MRI findings.

[MR contrast media for cardiovascular imaging]. / Anwendung von Kontrastmitteln für die kardiale Magnetresonanztomographie.

MR contrast media improve the diagnostic capability of MRI and MRA. They are used in the discrimination of viable and non-viable myocardium, transmural and non-transmural infarction, occlusive and reperfused infarction and for measurement of myocardial perfusion. Currently, clinical studies are almost completely restricted to the use of extracellular non-specific MR contrast media (i. e., Gd-DTPA, Gd-DTPA,-BMA, Gd-BOPTA, Gd-D03A). However, the feasibility of using intravascular, necrosis specific or intracellular MR contrast media or endogeneous substrates as specific MR contrast media in cardiovascular imaging has been demonstrated in experimental and a few clinical studies. Intravascular contrast media (i. e., MS-325 or NC100150 Injection) allow assessment of microvascular integrity and performance of MR angiography. Necrosis specific contrast media (i. e., Gadophrin-2) have been used for sizing the extent of infarcted myocardium while intracellular contrast media (i. e., Mn-DPDP) delineate viable myocardium. Endogenous contrast media (i. e., Deoxyhemoglobin, Na (+) or K (+)) have been tested for detecting the alterations in concentrations of these ions in infarcted myocardium and for perfusion measurements. Furthermore, intravascular MR contrast media may be useful for MRA and MRI guided cardiovascular interventions.