Suppression of the vacuum space-charge effect in fs-photoemission by a retarding electrostatic front lens.

The performance of time-resolved photoemission experiments at fs-pulsed photon sources is ultimately limited by the e-e Coulomb interaction, downgrading energy and momentum resolution. Here, we present an approach to effectively suppress space-charge artifacts in momentum microscopes and photoemission microscopes. A retarding electrostatic field generated by a special objective lens repels slow electrons, retaining the k-image of the fast photoelectrons. The suppression of space-charge effects scales with the ratio of the photoelectron velocities of fast and slow electrons. Fields in the range from -20 to -1100 V/mm for Ekin = 100 eV to 4 keV direct secondaries and pump-induced slow electrons back to the sample surface. Ray tracing simulations reveal that this happens within the first 40 to 3 µm above the sample surface for Ekin = 100 eV to 4 keV. An optimized front-lens design allows switching between the conventional accelerating and the new retarding mode. Time-resolved experiments at Ekin = 107 eV using fs extreme ultraviolet probe pulses from the free-electron laser FLASH reveal that the width of the Fermi edge increases by just 30 meV at an incident pump fluence of 22 mJ/cm2 (retarding field -21 V/mm). For an accelerating field of +2 kV/mm and a pump fluence of only 5 mJ/cm2, it increases by 0.5 eV (pump wavelength 1030 nm). At the given conditions, the suppression mode permits increasing the slow-electron yield by three to four orders of magnitude. The feasibility of the method at high energies is demonstrated without a pump beam at Ekin = 3830 eV using hard x rays from the storage ring PETRA III. The approach opens up a previously inaccessible regime of pump fluences for photoemission experiments.

The TRIXS end-station for femtosecond time-resolved resonant inelastic x-ray scattering experiments at the soft x-ray free-electron laser FLASH.

We present the experimental end-station TRIXS dedicated to time-resolved soft x-ray resonant inelastic x-ray scattering (RIXS) experiments on solid samples at the free-electron laser FLASH. Using monochromatized ultrashort femtosecond XUV/soft x-ray photon pulses in combination with a synchronized optical laser in a pump-probe scheme, the TRIXS setup allows measuring sub-picosecond time-resolved high-resolution RIXS spectra in the energy range from 35 eV to 210 eV, thus spanning the M-edge (M1 and M2,3) absorption resonances of 3d transition metals and N4,5-edges of rare earth elements. A Kirkpatrick-Baez refocusing mirror system at the first branch of the plane grating monochromator beamline (PG1) provides a focus of (6 × 6) µm2 (FWHM) at the sample. The RIXS spectrometer reaches an energy resolution of 35-160 meV over the entire spectral range. The optical laser system based on a chirped pulse optical parametric amplifier provides approximately 100 fs (FWHM) long photon pulses at the fundamental wavelength of 800 nm and a fluence of 120 mJ/cm2 at a sample for optical pump-XUV probe measurements. Furthermore, optical frequency conversion enables experiments at 400 nm or 267 nm with a fluence of 80 and 30 mJ/cm2, respectively. Some of the first (pump-probe) RIXS spectra measured with this setup are shown. The measured time resolution for time-resolved RIXS measurements has been characterized as 287 fs (FWHM) for the used energy resolution.

Time- and momentum-resolved photoemission studies using time-of-flight momentum microscopy at a free-electron laser.

Time-resolved photoemission with ultrafast pump and probe pulses is an emerging technique with wide application potential. Real-time recording of nonequilibrium electronic processes, transient states in chemical reactions, or the interplay of electronic and structural dynamics offers fascinating opportunities for future research. Combining valence-band and core-level spectroscopy with photoelectron diffraction for electronic, chemical, and structural analyses requires few 10 fs soft X-ray pulses with some 10 meV spectral resolution, which are currently available at high repetition rate free-electron lasers. We have constructed and optimized a versatile setup commissioned at FLASH/PG2 that combines free-electron laser capabilities together with a multidimensional recording scheme for photoemission studies. We use a full-field imaging momentum microscope with time-of-flight energy recording as the detector for mapping of 3D band structures in (kx, ky, E) parameter space with unprecedented efficiency. Our instrument can image full surface Brillouin zones with up to 7 Å-1 diameter in a binding-energy range of several eV, resolving about 2.5 × 105 data voxels simultaneously. Using the ultrafast excited state dynamics in the van der Waals semiconductor WSe2 measured at photon energies of 36.5 eV and 109.5 eV, we demonstrate an experimental energy resolution of 130 meV, a momentum resolution of 0.06 Å-1, and a system response function of 150 fs.

Non-linear soft x-ray methods on solids with MUSIX-the multi-dimensional spectroscopy and inelastic x-ray scattering endstation.

With the intense and coherent x-ray pulses available from free-electron lasers, the possibility to transfer non-linear spectroscopic methods from the laser lab to the x-ray world arises. Advantages especially regarding selectivity and thus information content as well as an improvement of signal levels are expected. The use of coherences is especially fruitful and the example of coherent x-ray/optical sum-frequency generation is discussed. However, many non-linear x-ray methods still await discovery, partially due to the necessity for extremely adaptable and versatile instrumentation that can be brought to free-electron lasers for the analysis of the spectral content emitted from the sample into a continuous range of emission angles. Such an instrument (called MUSIX) is being developed and employed at FLASH, the free-electron laser in Hamburg and is described in this contribution together with first results.

Human mesenchymal stromal cells inhibit platelet activation and aggregation involving CD73-converted adenosine.

BACKGROUND: Mesenchymal stromal cells (MSCs) are promising cell therapy candidates. Clinical application is considered safe. However, minor side effects have included thromboembolism and instant blood-mediated inflammatory reactions suggesting an effect of MSC infusion on hemostasis. Previous studies focusing on plasmatic coagulation as a secondary hemostasis step detected both procoagulatory and anticoagulatory activities of MSCs. We now focus on primary hemostasis and analyzed whether MSCs can promote or inhibit platelet activation. METHODS: Effects of MSCs and MSC supernatant on platelet activation and function were studied using flow cytometry and further platelet function analyses. MSCs from bone marrow (BM), lipoaspirate (LA) and cord blood (CB) were compared to human umbilical vein endothelial cells or HeLa tumor cells as inhibitory or activating cells, respectively. RESULTS: BM-MSCs and LA-MSCs inhibited activation and aggregation of stimulated platelets independent of the agonist used. This inhibitory effect was confirmed in diagnostic point-of-care platelet function analyses in platelet-rich plasma and whole blood. Using inhibitors of the CD39-CD73-adenosine axis, we showed that adenosine produced by CD73 ectonucleotidase activity was largely responsible for the LA-MSC and BM-MSC platelet inhibitory action. With CB-MSCs, batch-dependent responses were obvious, with some batches exerting inhibition and others lacking this effect. CONCLUSIONS: Studies focusing on plasmatic coagulation suggested both procoagulatory and anticoagulatory activities of MSCs. We now show that MSCs can, dependent on their tissue origin, inhibit platelet activation involving adenosine converted from adenosine monophosphate by CD73 ectonucleotidase activity. These data may have strong implications for safety and risk/benefit assessment regarding MSCs from different tissue sources and may help to explain the tissue protective mode of action of MSCs. The adenosinergic pathway emerges as a key mechanism by which MSCs exert hemostatic and immunomodulatory functions.

Time-resolved measurement of interatomic coulombic decay in Ne2.

The lifetime of interatomic Coulombic decay (ICD) [L. S. Cederbaum et al., Phys. Rev. Lett. 79, 4778 (1997)] in Ne2 is determined via an extreme ultraviolet pump-probe experiment at the Free-Electron Laser in Hamburg. The pump pulse creates a 2s inner-shell vacancy in one of the two Ne atoms, whereupon the ionized dimer undergoes ICD resulting in a repulsive Ne+(2p(-1))-Ne+(2p(-1)) state, which is probed with a second pulse, removing a further electron. The yield of coincident Ne+-Ne2+ pairs is recorded as a function of the pump-probe delay, allowing us to deduce the ICD lifetime of the Ne2(+)(2s(-1)) state to be (150±50) fs, in agreement with quantum calculations.

A change in the epidemiology of bovine cysticercosis in Israel between 1973 and 2008 due to import of live cattle.

Bovine cysticercosis (BC) is an important disease because of its zoonotic nature. There is a significant variation in the prevalence of BC in different countries, ranging from <0.01% to more than 20%. In this study, we followed the changes of BC prevalence in Israel during the last four decades and examined its association with import of live cattle. During 1973-2007, 629,549 cattle were subjected to post-mortem inspection conducted in 'Marbek' slaughterhouse located in the south of Israel. A specific comparison was made between the prevalence of BC in local and imported cattle during 2003-2007. Of 629,549 cattle, 2568 were infected with Cysticercus bovis (0.4%). From 1980, there was a gradual decrease in the prevalence of BC (R(2) = 0.53) with exceptional peaks. Moreover, from 1973 to 1998, only 4% of the documented cases appeared in outbreaks as opposed to 38% after 1998 when mass importation of live cattle to Israel was initiated. All of these late outbreak cases appeared in imported cattle of which 95% originated from Australia. During the years 2002-2007, importation from Australia was found as a significant risk factor for infection with BC, with prevalence in these cattle reaching 1.8% in 2006. The time from importation to BC detection suggests that infection occurred either in Australia or during the transport into Israel. We conclude that despite a reduction in the prevalence of BC as a result of a possible improvement in sanitary conditions at the farms, meticulous meat inspection is still essential in Israel and possibly in other developed countries exporting and importing live cattle.

[Detection of colorectal findings for cancer prevention by immunochemical stool test with different sensitivity levels]. / Detektion von kolorektalen Befunden zur Darmkrebsprävention mit immunologischem Stuhltest in verschiedenen Empfindlichkeitsstufen.

Immunochemical stool blood tests have a significantly higher sensitivity for the detection of advanced neoplasia and colorectal cancer. Based on national and international studies it has been required to include them into the national cancer screening programme in Germany also. The sensitivity (detection limit) can be set by the manufacturer in order to achieve an optimal and balanced result between sensitivity and specificity. The present study was conducted with 639 patients who have undergone both the screening colonoscopy, as well as the immunochemical stool blood test. The test "immoCARE-C" provided by the company CARE diagnostica Laborreagenzien GmbH was used in the study. The test has been evaluated with seven levels of detection limits between 500  ng/mL and 25  ng/mL. The best sensitivity for detection of advanced lesions was demonstrated by a cut-off of 50 ng/mL and 25  ng/mL. The specificity did not fall below 90  %. These positive results lead to considerations to organise a primary access to such tests in the prevention of colorectal cancer as a kind of filter before offering the screening colonoscopy.

Laser spectroscopy on forbidden transitions in trapped highly charged Ar(13+) ions.

We demonstrate resonant fluorescence laser spectroscopy in highly charged ions (HCI) stored in an electron beam ion trap by investigating the dipole-forbidden 1s(2)2s(2)2p (2)P(3/2)-(2)P(1/2) transition in boronlike Ar(13+) ions. Forced evaporative cooling yielded a high resolving power, resulting in an accurate wavelength determination to λ=441.255 68(26) nm. By applying stronger cooling and two-photon excitation, new optical frequency standards based upon ultrastable transitions in such HCI could be realized in the future, e.g., for the search of time variations of the fine-structure constant.

Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study.

AIMS/HYPOTHESIS: We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study. METHODS: We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312. RESULTS: We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. The GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group. CONCLUSIONS/INTERPRETATION: The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.

Imaging and therapy of experimental schwannomas using HSV amplicon vector-encoding apoptotic protein under Schwann cell promoter.

Schwannomas are benign tumors forming along peripheral nerves that can cause deafness, pain and paralysis. Current treatment involves surgical resection, which can damage associated nerves. To achieve tumor regression without damage to nerve fibers, we generated an HSV amplicon vector in which the apoptosis-inducing enzyme, caspase-1 (ICE), was placed under the Schwann cell-specific P0 promoter. Infection of schwannoma, neuroblastoma and fibroblastic cells in culture with ICE under the P0 promoter showed selective toxicity to schwannoma cells, while ICE under a constitutive promoter was toxic to all cell types. After direct intratumoral injection of the P0-ICE amplicon vector, we achieved marked regression of schwannoma tumors in an experimental xenograft mouse model. Injection of this amplicon vector into the sciatic nerve produced no apparent injury to the associated dorsal root ganglia neurons or myelinated nerve fibers. The P0-ICE amplicon vector provides a potential means of 'knifeless resection' of schwannoma tumors by injection of the vector into the tumor with low risk of damage to associated nerve fibers.

[Diagnoses as the subject of health service research to analyse the morbidity of outpatients]. / Diagnosen als Gegenstand der Versorgungsforschung zur Analyse der Morbidität ambulanter Patienten.

Health service research needs coded diagnoses of outpatients. The morbidity treated by physicians in ambulatory care is analysed every quarter on the basis of the diagnoses of about 1,2 Mio. patients by a randomised panel. Patient data combined with diagnoses, encounters and procedures demonstrate the variety of medical care provided. Relevant research questions are for instance the influence of co-payment on the structure of diagnoses or the prevalence of heart diseases in the offices of general practitioners. The comparison of prescribing patterns and diagnoses demonstrates the predominantly probatory therapy with proton pump-inhibitors in the case of gastroesophegal reflux disease. The plausibility and validity of disease documentation are permanently observed by regular checks.

Soft x-ray laser spectroscopy on trapped highly charged ions at FLASH.

In a proof-of-principle experiment, we demonstrate high-resolution resonant laser excitation in the soft x-ray region at 48.6 eV of the 2 (2)S(1/2) to 2 (2)P(1/2) transition of Li-like Fe23+ ions trapped in an electron beam ion trap by using ultrabrilliant light from Free Electron Laser in Hamburg (FLASH). High precision spectroscopic studies of highly charged ions at this and upcoming x-ray lasers with an expected accuracy gain up to a factor of a thousand, become possible with our technique, thus potentially yielding fundamental insights, e.g., into basic aspects of QED.

Relativistic electron correlation, quantum electrodynamics, and the lifetime of the 1s(2)2s(2)2p2p0(3/2) level in boronlike argon.

The lifetime of the Ar13+ 1s(2)2s(2)2p2p0(3/2) metastable level was determined at the Heidelberg Electron Beam Ion Trap to be 9.573(4)(5). The accuracy level of one per thousand makes this measurement sensitive to quantum electrodynamic effects like the electron anomalous magnetic moment (EAMM) and to relativistic electron-electron correlation effects like the frequency-dependent Breit interaction. Theoretical predictions, adjusted for the EAMM, cluster about a lifetime that is approximately shorter than our experimental result.

State-selective quantum interference observed in the recombination of highly charged Hg 75+...78+ mercury ions in an electron beam ion trap.

We present experimental data on the state-selective quantum interference between different pathways of photorecombination, namely, radiative and dielectronic recombination, in the KLL resonances of highly charged mercury ions. The interference, observed for well resolved electronic states in the Heidelberg electron beam ion trap, manifests itself in the asymmetry of line shapes, characterized by "Fano factors," which have been determined with unprecedented precision, as well as their excitation energies, for several strong dielectronic resonances.

[Glaucoma in practices of ophthalmologists]. / Verbreitung des Glaukoms unter Augenarztpatienten.

The aim of this study is to describe the prevalence of glaucoma among patients of office-based ophthalmologists on the basis of accounting data. The data can be taken from the so-called Patient-physician-panel for morbidity analysis (ADT panel) that has been developed by the Central Research Institute of Ambulatory Health Care in Germany. In this panel, the treatment data of patients treated by selected office-based physicians in North Rhine and Brandenburg are included. In both regions, 30 ophthalmologists were involved in the survey. The two random samples that have been performed, include the treatment data of nearly 55,000 patients from North-Rhine and of 58,000 patients from Brandenburg. The treatment prevalence of glaucoma with established diagnosis amounts to about 12% of the ophthalmologic patients in North Rhine and to about 13% in Brandenburg. If these figures are secondarily related to the total number of persons older than 39 years who are insured via social health insurance funds in these regions, the rates are 2.8 or 2.9% respectively. The majority of patients suffering from glaucoma (including suspected cases and exclusion diagnoses) underwent tonometry and it can be assumed that most of the patients received medical treatment. With the help of the morbidity panel, glaucoma patients with established diagnosis can be distinguished from those patients for whom this diagnosis has only been excluded and from cases where the suspicion remained unconfirmed. The standardised treatment prevalence of glaucoma almost amounts to the same rate in both regions. Ophthalmologists should use the additional specifications of the ICD-10 code more often (especially for cases of suspicion and exclusion). This would also lead to a higher significance of the ICD-10 terms indicated.

[Special applications in health telematics: electronic prescription/electronic patient file/digital archiving]. / Spezielle Anwendungen in der Gesundheitstelematik--Elektronisches Rezept/Elektronische Patientenakte/Digitale Archivierung.

Our challenge for the upcoming years is the development and the implementation of telematic applications that allow the exchange of data between different sectors of the health care system by a network system. Although most of the techniques already exist today, our highly administrated health care system makes further developments difficult. The communication process is subject to conventional procedures that have to be agreed upon between the contracting parties. The aim is to implement a common electronic communication platform for the health care system which can be accessed by all users. For this purpose, the implementation of electronic prescriptions (digital transmission of data that are up to now communicated from the physicians' office to the pharmacy in paper form) and of electronic patient files (structured documentations of findings according to standards agreed upon between the contracting parties) are of fundamental importance.

[Outpatient treatment of patients with cardiovascular diseases]. / Behandlung von Patienten mit Kreislauferkrankungen in der Arztpraxis.

In Germany, cardiovascular disturbances belong to the diseases most frequently treated in the offices of general practitioners and internal specialists. With comprehensive monitoring and the taking of adequate therapeutic measures, the average mortality age of the majority of the 18 million patients suffering from circulatory diseases lies at 79.4 years. In the age group of over 70 years, 70 to 80% of the patients receive treatment against cardiovascular disturbances, most of them against hypertension. One of the most important goals of monitoring and intervention in the outpatient sector is the treatment of hypertension, especially in connection with measures taken against disturbances in lipometabolism in order to prevent secondary diseases. The success of treatment is shown by the decreasing age standardized rate of cardiac infarctions, especially among men, and the decreasing mortality rate of patients below 65. The increasing treatment in the outpatient sector is accompanied by additional interventions, especially by bypass surgery in the hospital sector. The concerted actions in both the outpatient and the inpatient sector result in a higher service provision to come to a higher quality of life in the patients and to prevent early death.