Photon-recoil imaging: Expanding the view of nonlinear x-ray physics.

Addressing the ultrafast coherent evolution of electronic wave functions has long been a goal of nonlinear x-ray physics. A first step toward this goal is the investigation of stimulated x-ray Raman scattering (SXRS) using intense pulses from an x-ray free-electron laser. Earlier SXRS experiments relied on signal amplification during pulse propagation through dense resonant media. By contrast, our method reveals the fundamental process in which photons from the primary radiation source directly interact with a single atom. We introduce an experimental protocol in which scattered neutral atoms rather than scattered photons are detected. We present SXRS measurements at the neon K edge and a quantitative theoretical analysis. The method should become a powerful tool in the exploration of nonlinear x-ray physics.

A setup for element specific magnetization dynamics using the transverse magneto-optic Kerr effect in the energy range of 30-72 eV.

In this paper, we present a spectrometer that is designed for element-specific and time-resolved transverse magneto-optic Kerr effect experiments at the high-harmonic generation pump-probe facility High Energy Laser Induced Overtone Source (HELIOS) laboratory. HELIOS delivers photons with energies between 30 eV and 72 eV with an overall time resolution of less than 40 fs. The spectrometer is based on a Rowland-circle geometry and allows for simultaneous measurements of all magnetic transition-metal elements. The setup also features easy sample transfer and alignment, and it combines high photon throughput, optimized data acquisition, and a fast switching of the magnetic field at the sample. The spectrometer performance is demonstrated by measuring the ultrafast demagnetization of permalloy. Our data are, for all practical purposes, identical to what have been reported in the earlier high-order harmonic generation work of a similar sample by Mathias et al. [Proc. Natl. Acad. Sci. U. S. A. 109, 4792-4797 (2012)], however, obtained within 15% of the acquisition time compared to their study. Furthermore, our data show a shift of the demagnetization curve of Ni relative to Fe, which has previously been interpreted as a delay of the Ni demagnetization to that of Fe [S. Mathias et al., Proc. Natl. Acad. Sci. U. S. A. 109, 4792-4797 (2012)].

Rydberg-resolved resonant inelastic soft x-ray scattering: dynamics at core ionization thresholds.

Resonant inelastic x-ray scattering spectra excited in the immediate vicinity of the core-level ionization thresholds of N2 have been recorded. Final states of well-resolved symmetry-selected Rydberg series converging to valence-level ionization thresholds with vibrational excitations are observed. The results are well described by a quasi-two-step model which assumes that the excited electron is unaffected by the radiative decay. This threshold dynamics simplifies the interpretation of resonant inelastic x-ray scattering spectra considerably and facilitates characterization of low-energy excited final states in molecular systems.

HELIOS--A laboratory based on high-order harmonic generation of extreme ultraviolet photons for time-resolved spectroscopy.

In this paper, we present the HELIOS (High Energy Laser Induced Overtone Source) laboratory, an in-house high-order harmonic generation facility which generates extreme ultraviolet (XUV) photon pulses in the range of 15-70 eV with monochromatized XUV pulse lengths below 35 fs. HELIOS is a source for time-resolved pump-probe/two-color spectroscopy in the sub-50 fs range, which can be operated at 5 kHz or 10 kHz. An optical parametric amplifier is available for pump-probe experiments with wavelengths ranging from 240 nm to 20,000 nm. The produced XUV radiation is monochromatized by a grating in the so-called off-plane mount. Together with overall design parameters, first monochromatized spectra are shown with an intensity of 2 ⋅ 10(10) photons/s (at 5 kHz) in the 29th harmonic, after the monochromator. The XUV pulse duration is measured to be <25 fs after monochromatization.

High resolution multiphoton spectroscopy by a tunable free-electron-laser light.

Seeded free electron lasers theoretically have the intensity, tunability, and resolution required for multiphoton spectroscopy of atomic and molecular species. Using the seeded free electron laser FERMI and a novel detection scheme, we have revealed the two-photon excitation spectra of dipole-forbidden doubly excited states in helium. The spectral profiles of the lowest (-1,0)(+1) (1)S(e) and (0,1)(0) (1)D(e) resonances display energy shifts in the meV range that depend on the pulse intensity. The results are explained by an effective two-level model based on calculated Rabi frequencies and decay rates.

Nonstoichiometric intensities in core photoelectron spectroscopy.

X-ray photoemission spectroscopy is used in a great variety of research fields; one observable is the sample's stoichiometry. The stoichiometry can be deduced based on the expectation that the ionization cross sections for innershell orbitals are independent of the molecular composition. Here we used chlorine-substituted ethanes in the gas phase to investigate the apparent carbon stoichiometry. We observe a nonstoichiometric ratio for a wide range of photon energies, the ratio exhibits x-ray-absorption fine structure spectroscopy (EXAFS)-like oscillations and hundreds of eV above the C1s ionization approaches a value far from 1. These effects can be accounted for by considering the scattering of the outgoing photoelectron, which we model by multiple-scattering EXAFS calculations, and by considering the effects of losses due to monopole shakeup and shakeoff and to intramolecular inelastic scattering processes.

Excitation of 1S and 3S metastable helium atoms to doubly excited states.

We present spectra of triplet and singlet metastable helium atoms resonantly photoexcited to doubly excited states. The first members of three dipole-allowed ;{1,3}P;{o} series have been observed and their relative photoionization cross sections determined, both in the triplet (from 1s2s ;{3}S;{e}) and singlet (from 1s2s ;{1}S;{e}) manifolds. The intensity ratios are drastically different with respect to transitions from the ground state. When radiation damping is included the results for the singlets are in agreement with theory, while for triplets spin-orbit interaction must also be taken into account.

Toxicology case of the month: Carbamazepine overdose.

A 29-year-old woman presents shortly after a massive overdose of carbamazepine controlled-release tablets. In anticipation of coma, she is electively intubated to safely enable gastrointestinal decontamination with nasogastric activated charcoal. She is admitted to the intensive care unit for ongoing supportive care, and further doses of activated charcoal are prescribed to enhance elimination of carbamazepine. Carbamazepine levels remain high and haemodialysis is carried out to further enhance elimination. Her coma resolves as levels fall, but clinical progress is complicated by anticholinergic delirium, ileus and bowel obstruction from charcoal concretions. She survives to medical discharge on day 12.

Toxicology case of the month: oral hypoglycaemic overdose.

A teenager ingests 375 mg of glipizide and 14.5 g of melformin intentionally in a small country town. She presents to the local medical facility with symptoms and signs of hypoglycaemia. Using a risk assessment based approach, the management of suiphonylurea and metformin overdose is discussed. Sulphonylurea overdose invariably results in profound hypoglycaemia that requires resuscitation with IV dextrose and the use of octreotide as an antidote. Metfonnin overdose rarely causes problems.

Evaluation of a new immunoturbidimetric test (Liatest antithrombin III) for determination of antithrombin antigen.

Antithrombin (AT) is a glycoprotein mainly synthesised in the liver, and is one of the most important inhibitors of coagulation. Although AT activity determination is more important in clinical practice and anti-IIa and anti-Xa chromogenic tests are widely available, sometimes AT antigen measurement is preferred. Immunoradiometric and enzyme linked immunoabsorbent assay (ELISA) tests have been the only methods available so far for AT antigen determination, but both of them are relatively complicated, time consuming, and the ELISA test cannot be used for single sample assessment. A new immunoturbidimetric test (Liatest antithrombin III) is now available. We have adapted it for the Cobas Mira biomedical analyser. The intra- and inter-assay and total coefficients of variation for normal and low control plasma, as well as for normal pool plasma were low (< 3%). Blood samples from 32 patients with different clinical conditions were assessed both by the standard ELISA method and by the immunoturbidimetric method. The correlation coefficient was 0.95. According to our findings it seems that the immunoturbidimetric test (Liatest antithrombin III) for determination of AT antigen automated for the Cobas Mira biochemical analyser is easy to perform, time sparing and precise, with good comparability to other assays. It is suitable for measuring of AT antigen in routine laboratory work.

Tardive dyskinesia: dental prosthetic therapy.

The object of this study was to demonstrate that the dental prosthetic therapy that has long been shown to be effective in the treatment of idiopathic ov Spontaneous Orofacial Dyskinesia (SOFD) was also effective in the treatment of the orofacial manifestations of Tardive Dyskinesia (TD). This preliminary work consisted of evaluation of the results of dental prosthetic treatment provided to TD patients at the University of Illinois, College of Dentistry at Chicago. All patients who presented demonstrating orofacial manifestations of TD were accepted for treatment. No standard dental appliance exists to treat either SOFD or TD. Each case requires an individualized approach. Natural teeth should be maintained because the more natural teeth present, the easier it is to fabricate a stable and effective prosthesis, and TD occurs with greater frequency and severity in edentulous than in dentulous patients. Effective treatment of such patients requires the dentist to be flexible and tailor his therapy to idiosyncrasies of each case, rather than being wedded to rigid theories of what is supposed to be appropriate treatment and appliance design. Two representative cases of treatment of TD with dental prostheses are presented. Prosthetic dental therapy should be considered in the management of the orofacial manifestations of Tardive Dyskinesia because it often is effective and has no known side effects. Since the treatment described here is prosthetic, any team approach to the treatment of TD should include an interested general dentist or prosthodonist.

Linell classification of breast cancer morphology compared to histologic grading, S-phase fraction and DNA-ploidy.

One hundred and fifty-eight histologically verified mammary carcinomas with known mammographic doubling time (DT) were studied with special emphasis on a morphologic classification proposed by Linell et al. [8, 12, 14, 15]. The hypothesis that Linell classification of ductal carcinomas into comedo, tubuloductal and tubular carcinomas is easy to perform with small inter-observer variations, was not fully confirmed. The Linell classification was found to correlate well with conventional WHO malignancy grading, S-phase fraction and DNA-ploidy. The Linell classification also correlated to surgical stage, lymph node status and DT, but not at all to tumour size. Using distant disease-free survival as an endpoint, the Linell classification gave prognostic information comparable to conventional histologic grading, seeming to be a simple, cheap and reliable method well worth trying on a larger scale.

Reasons for cervical cancer despite extensive screening.

OBJECTIVE: To explain an age adjusted incidence rate of cervical cancer of 10.1 and 10.5 per 100,000 women, despite extensive screening. SETTING: The Swedish county of Gävleborg in 1986 and 1987. METHODS: Thirty eight patients with "cervical cancer" reported to the central cancer registry in Sweden were investigated. The patients and their diagnoses were scrutinised in a double blind manner. RESULTS: Eighteen per cent (7/38) of cases were shown to be mistakes in data transfer; 11% (4/38) of cases were endocervical adenocarcinomas; 13% (5/38) were histopathological misinterpretations and should have been reported as carcinoma in situ. Of the remaining 22 patients with invasive squamous cancer, 12 (55%) had not participated in the gynaecological health control programme. Of the 10 participants with invasive squamous cancer despite this participation, eight (80%) had repeatedly had abnormal Papanicolaou smears without further gynaecological/histopathological examination and treatment. There was no evidence of cases of carcinoma in situ or endometrial cancer diagnosed in 1986-87 being squamous cervix cancer. The true incidence of squamous cervical cancer among participants was 3.0 per 100,000 for the two years scrutinised. If all the patients with Papanicolaou smear abnormalities had been properly managed at the right time, and the treatment had been successful, the incidence of invasive squamous cancer would have been 0.8 per 100,000 women among participants as opposed to 38.2 per 100,000 among non-participants. CONCLUSION: The evidence strongly suggests overascertainment of cervical cancer, which conceals the success of screening, and also suggests that much attention must be given to clinical management of detected lesions in cervical screening. Care is needed in applying accurate histopathological criteria when making a diagnosis of invasive squamous cancer, to separate squamous cancer from other malignant tumours of the cervix, and in data transfer to cancer registries.

A late exclusion of bacteriophage T4 can be suppressed by Escherichia coli GroEL or Rho.

A litCon mutation in Escherichia coli TU6 results in exclusion of bacteriophage T4 during the late, morphogenetic stage of its development at low temperatures. DNA was synthesized continuously in the infected cells, but less than 10% of the DNA made by 90 min after infection was packaged into DNAase-resistant particles, few viable phage were formed, and the cells lysed poorly. The exclusion could be relieved by conditions leading to elevated levels, determined immunologically, of the E. coli Rho protein (believed to be involved in regulation of T4 transcription), or chromosomally encoded E. coli GroEL (a chaperone known to be involved in phage assembly), or by supplying GroEL in trans from a plasmid. The two suppressing proteins appeared to act independently of each other. GroEL-suppression restored packaging to normal levels, perhaps by preventing GP23 from activating the host Lit protein; in addition DNA synthesis was delayed and reduced and cell lysis enhanced, demonstrating involvement of GroEL in both these processes. Rho suppression was less efficient. Since both transcription-termination-proficient and transcription-termination-deficient Rho suppressed, the results raise the possibility that Rho has a role during T4 development not directly involving transcription regulation.

Breast carcinoma growth rate described by mammographic doubling time and S-phase fraction. Correlations to clinical and histopathologic factors in a screened population.

BACKGROUND: In a retrospective study, correlations among mammographic doubling times (DT), clinicopathologic prognostic factors, and cytometric predictors were examined. METHODS: One hundred fifty-eight patients with the possibility to calculate mammographic tumor DT were selected and the tumors were histologically reexamined and flow cytometric analysis for ploidy and S-phase fraction (SPF) was performed. RESULTS: The tumors were Stage I in 68%, and 45% were detected by mammographic screening. DT ranged from 0.6 months to an indefinite time (median, 9.0 months). Short DT was significantly correlated to large tumor size (P = 0.01) and advanced pathologic tumor stage (P = 0.016), but there was no correlation between DT and histologic grade. Ploidy analysis indicated that there were 57% aneuploid and 7% tetraploid tumors. There was a significant overrepresentation of euploid tumors among tumors smaller than 10 mm (P = 0.02). Ploidy was correlated to histologic grade (P less than 0.001) and DT (P = 0.009). SPF was calculated in 122 cases. SPF correlated significantly with pathologic stage (P = 0.002), tumor size (P = 0.037), histologic grade (P = 0.001), the presence of axillary lymph node metastases (P = 0.046), DT (P = 0.02), and DNA ploidy (P less than 0.001). Compared with interval carcinoma, screening-detected carcinoma showed favorable characteristics concerning size, stage, DT, ploidy, and SPF but not regarding histologic grade and axillary lymph node metastases. CONCLUSIONS: DT shows great variations. Factors related to tumor biology (i.e., DT, DNA ploidy, and SPF) are strongly correlated with one another, but they have no correlation with axillary lymph node metastases. Cancer detected by screening is discovered at an early stage and shows favorable characteristics concerning DT, ploidy, and SPF.

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND: The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS: The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS: In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS: SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.

Automatic analysis of Papanicolaou smears by digital image processing.

Papanicolaou smears from 378 patients were analyzed in a fully automated microscope system using an image analysis technique. The logic of the system subdivided the smears into "normal" (63%), "not possible to analyze in the machine" (17%) and "positive" (20%). The results have been compared with the conventional screening method available today taking into consideration the definition problems of a true diagnosis, cytopathological and histopathological consensus, reproducibility, sample-taking and interpretation mistakes, etc. As 37% (rejected and positive) of the smears in this particular study were analyzed visually after machine prescreening, it could be demonstrated that the false-negative rate among the remaining 63% of the specimens was significantly lower among the machine-screened smears when compared with visual screening if the results were correlated with histopathological consensus. The results clearly indicate that the technology required to build computerized microscope systems, which are able to automatically sort out at least two thirds of Papanicolaou smears is available today. The only limiting factor is the cost-benefit relationship.

Breast hamartomas. An important entity in mammary pathology.

1. Fifteen cases of a rather distinct entity of tumour-like lesion in the breast are presented. 2. They have a distinct mammographic appearance and can be easily shelled out at surgery, leaving symmetrical breasts. 3. They are well-circumscribed lumps of varying size with a smooth surface. 4. Microscopically they show normal or dysplastic glandular structures of lobules and ducts, without neoplastic features, within a prominent fibrous stroma. The lesions appear to be closely related to adenolipomas.