The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Transient magnetic gratings on the nanometer scale.

Laser-driven non-local electron dynamics in ultrathin magnetic samples on a sub-10 nm length scale is a key process in ultrafast magnetism. However, the experimental access has been challenging due to the nanoscopic and femtosecond nature of such transport processes. Here, we present a scattering-based experiment relying on a laser-induced electro- and magneto-optical grating in a Co/Pd ferromagnetic multilayer as a new technique to investigate non-local magnetization dynamics on nanometer length and femtosecond timescales. We induce a spatially modulated excitation pattern using tailored Al near-field masks with varying periodicities on a nanometer length scale and measure the first four diffraction orders in an x-ray scattering experiment with magnetic circular dichroism contrast at the free-electron laser facility FERMI, Trieste. The design of the periodic excitation mask leads to a strongly enhanced and characteristic transient scattering response allowing for sub-wavelength in-plane sensitivity for magnetic structures. In conjunction with scattering simulations, the experiment allows us to infer that a potential ultrafast lateral expansion of the initially excited regions of the magnetic film mediated by hot-electron transport and spin transport remains confined to below three nanometers.

Extracting depth information of 3-dimensional structures from a single-view X-ray Fourier-transform hologram.

We demonstrate how information about the three-dimensional structure of an object can be extracted from a single Fourier-transform X-ray hologram. In contrast to lens-based 3D imaging approaches that provide depth information of a specimen utilizing several images from different angles or via adjusting the focus to different depths, our method capitalizes on the use of the holographically encoded phase and amplitude information of the object's wavefield. It enables single-shot measurements of 3D objects at coherent X-ray sources. As the ratio of longitudinal resolution over transverse resolution scales proportional to the diameter of the reference beam aperture over the X-ray wavelength, we expect the approach to be particularly useful in the extreme ultraviolet and soft-X-ray regime.

Monolithic focused reference beam X-ray holography.

Fourier transform holography is a highly efficient and robust imaging method, suitable for single-shot imaging at coherent X-ray sources. In its common implementation, the image contrast is limited by the reference signal generated by a small pinhole aperture. Increased pinhole diameters improve the signal, whereas the resolution is diminished. Here we report a new concept to decouple the spatial resolution from the image contrast by employing a Fresnel zone plate to provide the reference beam. Superimposed on-axis images of distinct foci are separated with a novel algorithm. Our method is insensitive to mechanical drift or vibrations and allows for long integration times common at low-flux facilities like high harmonic generation sources. The application of monolithic focused reference beams improves the efficiency of high-resolution X-ray Fourier transform holography beyond all present approaches and paves the path towards sub-10 nm single-shot X-ray imaging.

Exploration of magnetic fluctuations in PdFe films.

We investigated magnetic phase transitions, magnetic anisotropy, and magnetic domains in Pd1-xFex alloys with different Fe concentrations x = 2.2-7.2%. The Curie temperature depends linearly on the Fe concentration in the regime studied. The magnetization is dominantly in-plane with a small out-of-plane remanent contribution. Resonant magnetic small angle scattering with circularly polarized x-rays tuned to the L3 resonance edge of Fe revealed a small angle scattering ring corresponding to magnetic domain fluctuations on a length scale of 100 nm. These fluctuations are isotropically distributed in the film plane and appear to have an out-of-plane component. On increasing the transverse coherence of the incident beam, the scattering ring decomposes in a speckle pattern, indicative of magnetic correlations on a length scale smaller than the x-ray coherence length of about 4 µm.

Endstation for ultrafast magnetic scattering experiments at the free-electron laser in Hamburg.

An endstation for pump-probe small-angle X-ray scattering (SAXS) experiments at the free-electron laser in Hamburg (FLASH) is presented. The endstation houses a solid-state absorber, optical incoupling for pump-probe experiments, time zero measurement, sample chamber, and detection unit. It can be used at all FLASH beamlines in the whole photon energy range offered by FLASH. The capabilities of the setup are demonstrated by showing the results of resonant magnetic SAXS measurements on cobalt-platinum multilayer samples grown on freestanding Si(3)N(4) membranes and pump-laser-induced grid structures in multilayer samples.

Breakdown of the x-ray resonant magnetic scattering signal during intense pulses of extreme ultraviolet free-electron-laser radiation.

We present results of single-shot resonant magnetic scattering experiments of Co/Pt multilayer systems using 100 fs long ultraintense pulses from an extreme ultraviolet (XUV) free-electron laser. An x-ray-induced breakdown of the resonant magnetic scattering channel during the pulse duration is observed at fluences of 5 J/cm(2). Simultaneously, the speckle contrast of the high-fluence scattering pattern is significantly reduced. We performed simulations of the nonequilibrium evolution of the Co/Pt multilayer system during the XUV pulse duration. We find that the electronic state of the sample is strongly perturbed during the first few femtoseconds of exposure leading to an ultrafast quenching of the resonant magnetic scattering mechanism.

Ultrafast optical demagnetization manipulates nanoscale spin structure in domain walls.

During ultrafast demagnetization of a magnetically ordered solid, angular momentum has to be transferred between the spins, electrons, and phonons in the system on femto- and picosecond timescales. Although the intrinsic spin-transfer mechanisms are intensely debated, additional extrinsic mechanisms arising due to nanoscale heterogeneity have only recently entered the discussion. Here we use femtosecond X-ray pulses from a free-electron laser to study thin film samples with magnetic domain patterns. We observe an infrared-pump-induced change of the spin structure within the domain walls on the sub-picosecond timescale. This domain-topography-dependent contribution connects the intrinsic demagnetization process in each domain with spin-transport processes across the domain walls, demonstrating the importance of spin-dependent electron transport between differently magnetized regions as an ultrafast demagnetization channel. This pathway exists independent from structural inhomogeneities such as chemical interfaces, and gives rise to an ultrafast spatially varying response to optical pump pulses.

Holographically aided iterative phase retrieval.

Fourier transform holography (FTH) is a noise-resistant imaging technique which allows for nanometer spatial resolution x-ray imaging, where the inclusion of a small reference scattering object provides the otherwise missing phase information. With FTH, one normally requires a considerable distance between the sample and the reference to ensure spatial separation of the reconstruction and its autocorrelation. We demonstrate however that this requirement can be omitted at the small cost of iteratively separating the reconstruction and autocorrelation. In doing so, the photon efficiency of FTH can be increased due to a smaller illumination area, and we show how the presence of the reference prevents the non-uniqueness problems often encountered with plane-wave iterative phase retrieval. The method was tested on a cobalt/platinum multilayer exhibiting out of plane magnetized domains, where the magnetic circular dichroism effect was used to image the magnetic domains at the cobalt L3-edge at 780eV.

Osteopontin deficiency protects against obesity-induced hepatic steatosis and attenuates glucose production in mice.

AIMS/HYPOTHESIS: Obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). The cytokine osteopontin (OPN) was recently shown to be involved in obesity-induced adipose tissue inflammation and reduced insulin response. Accumulating evidence links OPN to the pathogenesis of NAFLD. Here we aimed to identify the role of OPN in obesity-associated hepatic steatosis and impaired hepatic glucose metabolism. METHODS: Wild-type (WT) and Opn (also known as Spp1) knockout (Opn (-/-)) mice were fed a high-fat or low-fat diet to study OPN effects in obesity-driven hepatic alterations. RESULTS: We show that genetic OPN deficiency protected from obesity-induced hepatic steatosis, at least in part, by downregulating hepatic triacylglycerol synthesis. Conversely, absence of OPN promoted fat storage in adipose tissue thereby preventing the obesity-induced shift to ectopic fat accumulation in the liver. Euglycaemic-hyperinsulinaemic clamp studies revealed that insulin resistance and excess hepatic glucose production in obesity were significantly attenuated in Opn (-/-) mice. OPN deficiency markedly improved hepatic insulin signalling as shown by enhanced insulin receptor substrate-2 phosphorylation and prevented upregulation of the major hepatic transcription factor Forkhead box O1 and its gluconeogenic target genes. In addition, obesity-driven hepatic inflammation and macrophage accumulation was blocked by OPN deficiency. CONCLUSIONS/INTERPRETATION: Our data strongly emphasise OPN as mediator of obesity-associated hepatic alterations including steatosis, inflammation, insulin resistance and excess gluconeogenesis. Targeting OPN action could therefore provide a novel therapeutic strategy to prevent obesity-related complications such as NAFLD and type 2 diabetes.

Rapid vinculin exchange dynamics at focal adhesions in primary osteoblasts following shear flow stimulation.

The adaptor protein vinculin plays a key position in the formation of focal adhesions and regulates cell attachment. To study the turnover of vinculin in bone-derived cells, we expressed green fluorescent protein-tagged vinculin in primary bovine osteoblasts and examined the appearance of focal adhesions in cells exposed to laminar shear flow. Already 20 sec after application of shear stress fluorescently labelled focal adhesions became visible as small flashing dots at the periphery of cells. The number of newly formed focal adhesions per individual cell increased continuously over approximately 300 sec and then remained relatively stable. The assembly of focal adhesions in shear stress-stimulated osteoblasts was accompanied by a transient rise in intracellular calcium levels. The mean assembly time of an individual focal adhesion plaque was 32.2+/-2.2 sec and the mean disassembly time was 60.5+/-6.0 sec. The recruitment of vinculin to nascent focal adhesions was in the same range as the recovery half-life of GFP-vinculin at stable focal adhesions (13.0+/-2.0 sec). These data show that accumulation of GFP-vinculin in newly formed focal adhesions and its exchange from pre-existing, mature plaques are both rapid processes that occur in mechanically stimulated osteoblasts within less than one minute.

Coherent-pulse 2D crystallography using a free-electron laser x-ray source.

Coherent diffractive imaging for the reconstruction of a two-dimensional (2D) finite crystal structure with a single pulse train of free-electron laser radiation at 7.97 nm wavelength is demonstrated. This measurement shows an advance on traditional coherent imaging techniques by applying it to a periodic structure. It is also significant that this approach paves the way for the imaging of the class of specimens which readily form 2D, but not three-dimensional crystals. We show that the structure is reconstructed to the detected resolution, given an adequate signal-to-noise ratio.

[Diffuse dermal angiomatosis]. / Diffuse dermale Angiomatose.

Diffuse dermal angiomatosis (DDA) is a benign, acquired vascular proliferation characterized by painful, poorly circumscribed, livid-erythematous plaques with frequent central ulceration. The clinical features are reminiscent of reactive angioendotheliomatosis or embolia cutis medicamentosa. Histologically, a dense diffuse network of regular capillary vessels throughout the dermis is seen. Endothelial atypia, atypical mitoses or signs of vasculitis are missing. A 43-year-old woman developed a bizarre brownish-livid rapidly growing lesion of DDA 8 centimeters above a surgical scar, shortly after removal of 20 kilograms of fatty tissue from the lower abdominal wall. DDA regressed spontaneously within 12 weeks, and has not recurred over 4 years of follow-up.

Ocular changes in mucopolysaccharidosis IV A (Morquio A syndrome) and long-term results of perforating keratoplasty.

BACKGROUND: The mucopolysaccharidoses (MPS) are an inhomogeneous group of disorders of errors in the carbohydrate metabolism with severe ocular involvement (corneal opacification, retinal degeneration, optic atrophy). PATIENT PRESENTATION: We report on a boy aged 12 years, with Morquio A (MPS IV A) syndrome. Ocular findings: progressive pseudoexophthalmus due to shallow orbits, increasing corneal stromal clouding, intermittent dissociated manifest nystagmus of the left eye, nyctalopia. Visual acuity OD cc = 0.16, OS cc = 0.05. Electrophysiology: changes suggesting a symptomatic tapetoretinal degeneration and optic atrophy. TREATMENT AND COURSE OF DISEASE: OS: perforating keratoplasty. Postoperative improvement of visual acuity to 0.25 for nearly a year, followed by progressive reopacification of the corneal graft. Both eyes: progressive signs of tapetoretinal degeneration and optic atrophy. Visual acuity now reduced to OD 0.05, OS 0.1. CONCLUSIONS: Success of a keratoplasty is limited by (1) reopacification of the cornea, (2) visual impairment due to (a) retinal degeneration and (b) optic atrophy. The indication for perforating keratoplasty has to be thought about very carefully in these multimorbid patients. In our patient, beside progressive visual impairment there is a progressive deafness which dominates his social and school life. Attending school is severely complicated by the double handicap. Perforating keratoplasty enabled the boy to attend a school for physically handicapped without a special low-vision care for another year. Progressive visual loss without further treatment options now renders optical and electronic low-vision aids necessary. Although the time of improved visual acuity lasted less than a year, we think patients with a life expectancy of less than 20 years should have every possible improvement of their situation - even if it does not last permanently. We therefore propose perforating keratoplasty in spite of insufficient long-term results.

[Screening for amblyopia, strabismus and refractive abnormalities in 1,030 kindergarten children]. / Screening-Untersuchung auf Amblyopie, Strabismus und Refraktionsanomalie bei 1030 Kindergartenkindern.

BACKGROUND: There are controversies concerning the necessity of pre-school vision screening. AIM OF THE STUDY: evaluation of the prevalence of pathologic ophthalmologic findings in kindergarten children. MATERIALS AND METHODS: 1030 families were offered a vision screening. Of these, a total of 948 children, aged 3 to 6 years, voluntarily underwent a screening for strabismus, amblyopia and refractive anomalies. The examination was performed in the kindergarten in the absence of the parents. METHODS OF EXAMINATION: A questionnaire concerning general and ophthalmologic history of the child and of the family was evaluated. Visual acuity, cover-uncover-test, Lang-stereotest, retinoscopy, ophthalmoscopy (undilated pupils) were performed and the glasses were evaluated. RESULTS: The screening was highly accepted by the parents and 92% of the families (n = 948) took part. The compliance of the children was very good. A total of 38.7% (n = 381) of the children showed one or more abnormal parameters. 21.4% (n = 229) showed a reduced visual acuity. Strabismus was found in 3.7%. Half of the children with abnormal findings already had had a vision screening, but only 25% had received ophthalmologic treatment. Of those who possessed glasses, 25% came without them, and another 25% had a reduced visual acuity even with their glasses. The main problems were many false-positive results and high costs. CONCLUSIONS: Ophthalmologic and orthoptic screening in kindergarten is technically easy and conclusive in experienced hands. Ideas to reduce costs and to avoid overreferrals are an age-related lowering of the visual acuity limit and a rescreening of suspected children in a screening-setting a second time before sending them to an ophthalmologist. Another possibility to reduce costs would be to perform examinations not by ophthalmologists but by "screening-orthoptists" who should be trained in retinoscopy and ophthalmoscopy.

[Eye and general illnesses in the public school for blind and visually handicapped students in Saarland. Developments in the last 20 years]. / Augen- und Allgemeinerkrankungen in der Landesschule für Blinde und Sehbehinderte des Saarlands. Entwicklungen in den letzten 20 Jahren.

BACKGROUND: The aim of the study was the evaluation of how ophthalmological diagnoses and the proportion of multiply handicapped children has changed within the last 20 years at a state school for visually handicapped and blind children. PATIENTS AND METHODS: A profile investigation was conducted on all 105 children at the Landesschule für Blinde und Sehbehinderte des Saarlandes and compared to the results of an examination from 1975. RESULTS: The predominant ophthalmological diagnoses were: optic atrophy (17.5%), ocular albinism (11.9%), scar-stage IV and V of retinopathy of prematurity (11.1%), as well as tapetoretinal dystrophies with related syndromes (8.7%) and myopia magna (7.9%). Blind: 10.3% (1975: 36.4%); visually handicapped: 47.1% (1975: 49.2%); multiply handicapped: 42.5% (1975: 14.4%). CONCLUSIONS: (1) The diseases that dominated in earlier years in schools for the visually handicapped have become rare (cataract, aphakia, buphthalmia, macular dystrophy--all less than 5%); (2) the proportion of completely blind pupils has become much smaller; (3) there is an increasing tendency to educate visually handicapped pupils in regular schools with integrative aids; (4) there is also an increasing proportion of multiply handicapped children (school and kindergarten: 42%, early patronage 74%).

Differentiating cyclic from chronic vomiting patterns in children: quantitative criteria and diagnostic implications.

OBJECTIVE: To establish criteria to differentiate two patterns of vomiting and to identify the predominant diagnoses for each group. METHODS: All children 2 to 18 years of age referred to a pediatric gastroenterology service who presented with recurrent vomiting (three episodes of vomiting within a 3-month period) as a primary complaint from 1985 to 1991 were retrospectively reviewed (n = 106). The vomiting pattern (emeses per hour and episodes per month), diagnostic studies, and therapeutic responses were compared by Mann-Whitney U and chi-squared tests. RESULTS: Based on the criteria of peak intensity (four or more emeses per hour) and frequency (nine or fewer episodes per month), two subgroups were differentiated: chilcren with a cyclic pattern (n = 34), who vomited at a higher peak intensity (12.6 +/- 1.6 vs 1.5 +/- 0.1 emeses per hour) but at a lower frequency (1.9 +/- 4.8 vs 36.6 +/-0.3 episodes per month) than those with a chronic pattern (n = 72). Among children with a cyclic patern, nongastrointestinal (65%) causes, especially peptic and infectiouus disorders, predominated over nongastrointestinal ones (10%). CONCLUSIONS: On the basis of quantitative historical criteria, children with recurrent vomiting can be classified into two subgroups that seem to be clinically and etiologically distinct. Abdominal migraine was the dominant diagnosis in those with cyclic vomiting, whereas peptic and infectious gastrointestinal disorders predominated in those with chronic vomiting. This differentiation between cyclic and chronic patterns of vomiting may be a useful diagnostic clue to the clinician.

[Comparison between local and systemic administration of cyclosporin A on the effective level in conjunctiva, aqueous humor and serum]. / Vergleich zwischen lokaler und systemischer Applikation von Cyclosporin A auf den Wirkspiegel in Bindehaut, Kammerwasser und Serum.

Cyclosporine is an important tool for the therapy of immunological diseases of the cornea and conjunctiva, as well as the treatment of patients with high-risk corneal grafts. However, potentially severe systemic side effects are disadvantageous. The purpose of our study was to determine if topical ocular application leads to about the same concentrations in ocular tissues as systemic application. Therefore, the concentration of cyclosporine in conjunctiva, aqueous humor and blood was measured by radioimmunoassay in six patients with systemic administration of cyclosporine and ten patients who received one drop of topical cyclosporine 2% four times prior to cataract surgery. All patients with systemic application showed measurable concentrations of cyclosporine in blood, as did four patients in the group receiving topical cyclosporine. There was no significant difference between both groups concerning cyclosporine concentration in aqueous humor. The level of cyclosporine in the conjunctiva was significantly higher after topical application (P < 0.02). In conclusion, therapy with cyclosporine eye drops results in levels in the conjunctiva and aqueous humor that are comparable to or even higher than those after systemic application if the last application was no more than 18h prior to the measurement. Therefore, topical ocular application of cyclosporine, which reduces or eliminates the drug's systemic side effects, can be used to induce local immunosuppressive activity, particularly in the treatment of superficial immunological diseases and after limbal allograft transplantation.

[Goniotrepanation combined with sinus surgery as a transitional measure in spontaneous carotid artery-cavernous sinus fistulas]. / Die Goniotrepanation in Kombination mit einer Sinusotomie als überbrückende Massnahme bei spontanen A.-carotis-Sinus-cavernosus-Fisteln.

Two patients with spontaneous, angiographically proven fistulas showed progressive ocular symptoms which precluded waiting for spontaneous occlusion of the fistulas. On the other hand, endovascular therapy of the carotid-cavernous fistulas was not possible because the arterial supply of the fistulas came from both internal carotids. Therefore filtering surgery was performed in the affected eyes. Postoperatively, intraocular pressure decreased to normal values in both patients and the symptoms resolved. The visual acuity increased in one patient and remained the same in the other. In conclusion, filtering surgery is an important therapeutic tool to preserve visual function in eyes with carotid-cavernous fistulas that display progressive ocular symptoms but cannot be treated by embolization.

[Prognosis of intralenticular lead foreign bodies]. / Zur Prognose intralentaler Bleifremdkörper.

BACKGROUND: The prognosis of intraocular foreign bodies consisting of lead remains controversial. While experiments have shown that infected lead becomes sterile when fired from rifles, both the total absence as well as presence of severe inflammation have been observed following perforating injuries with lead. Furthermore, alterations of the ERG have been described in experimental settings. This case report is presented in order to clarify the long term prognosis of intralenticular lead particles. PATIENT AND METHOD: The 69-year-old patient suffered from a bilateral perforating injury caused by a bullet during World War II (1942). The right lens was extracted due to a secondary cataract several weeks following the injury. The left lens remained clear despite a paracentrally located metallic foreign body. The patient underwent extracapsular cataract extraction in 1992 because of an opacity of the posterior capsule which was well separated from the foreign body. Preoperatively the ERG was normal. An energy dispersive X-ray microanalysis in a scanning electron microscope was performed in order to determine the chemical composition of the foreign body, and X-ray diffraction with a Gandolphi camera was used for its structural characterisation. The foreign body consists of lead. However, its surface is probably altered to lead oxide, hydroxide or carbonate, which hindered further reaction of the lead. Calcium phosphate was deposited on the walls of the foreign body. CONCLUSION: Our report shows that lead in the lens remains inert for several decades and does not cause alterations in the ERG. Therefore, intralenticular lead outside of the optical axis may be left in situ unless a secondary cataract develops.