Development of a 10 kHz high harmonic source up to 140 eV photon energy for ultrafast time-, angle-, and phase-resolved photoelectron emission spectroscopy on solid targets.

We present a newly developed high harmonic beamline for time-, angle-, and carrier-envelope phase-resolved extreme ultraviolet photoemission spectroscopy on solid targets for the investigation of ultrafast band structure dynamics in the low-fs to sub-fs time regime. The source operates at a repetition rate of 10 kHz and is driven by 5 fs few-cycle near-infrared laser pulses generating high harmonic radiation with photon energies up to 120 eV at a feasible flux. The experimental end station consists of a complementary combination of photoelectron detectors which are able to spectroscopically address electron dynamics both in real and in k-space. The versatility of the source is completed by a phase-meter which allows for tracking the carrier-envelope phase for each pulse and which is synchronized to the photoelectron detectors, thus enabling phase sensitive measurements on the one hand and the selection of single attosecond pulses for ultimate time resolution in pump-probe experiments on the other hand. We demonstrate the applicability of the source by an angle- and carrier-envelope phase-resolved photoemission measurement on a tungsten (110) surface with 95 eV extreme ultraviolet radiation.

Transverse Coherence Limited Coherent Diffraction Imaging using a Molybdenum Soft X-ray Laser Pumped at Moderate Pump Energies.

Coherent diffraction imaging (CDI) in the extreme ultraviolet has become an important tool for nanoscale investigations. Laser-driven high harmonic generation (HHG) sources allow for lab scale applications such as cancer cell classification and phase-resolved surface studies. HHG sources exhibit excellent coherence but limited photon flux due poor conversion efficiency. In contrast, table-top soft X-ray lasers (SXRL) feature excellent temporal coherence and extraordinary high flux at limited transverse coherence. Here, the performance of a SXRL pumped at moderate pump energies is evaluated for CDI and compared to a HHG source. For CDI, a lower bound for the required mutual coherence factor of |µ 12| ≥ 0.75 is found by comparing a reconstruction with fixed support to a conventional characterization using double slits. A comparison of the captured diffraction signals suggests that SXRLs have the potential for imaging micron scale objects with sub-20 nm resolution in orders of magnitude shorter integration time compared to a conventional HHG source. Here, the low transverse coherence diameter limits the resolution to approximately 180 nm. The extraordinary high photon flux per laser shot, scalability towards higher repetition rate and capability of seeding with a high harmonic source opens a route for higher performance nanoscale imaging systems based on SXRLs.

A Psychometric Evaluation of the German Version of the Quick Inventory of Depressive Symptomatology (QIDS-SR16) in Outpatients with Depression.

BACKGROUND: The self-rated, 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) is a well-established measure of depression severity. This study aimed to evaluate the psychometric properties of the German translation of the QIDS-SR16. METHODS: 332 depressed German adults awaiting psychotherapy were assessed with the German translations of the QIDS-SR16, the Beck Depression Inventory (BDI-II) and the 24-item Hamilton Rating Scale for Depression (HRSD-24). RESULTS: Internal consistency for the QIDS-SR16 was acceptable (Cronbach's alpha = .77). Corrected item-total correlations indicated adequate discriminatory power of all the items. The QIDS-SR16 highly correlated with the BDI-II (r = .810) but only moderately correlated with the HRSD-24 (r = .581). Regarding discriminant validity, the QIDS-SR16 discriminated between patients with and without a depressive episode but not between patients with and without panic disorder. CONCLUSION: The German translation of the QIDS-SR16 has adequate psychometric properties. Our results support the usefulness of the German version of the QIDS-SR16 as a brief depression rating scale in clinical and research settings.

Strategies to improve the outcome in locally advanced pancreatic cancer.

Pancreatic cancer is associated with the worst prognosis of all gastrointestinal malignancies. The major reasons for the dismal outcome are late diagnosis due to unspecific symptoms and aggressive tumor biology. Although highly effective chemotherapeutic options have emerged within the last decade, radical resection offers the only chance of cure. Only 10-20% of patients are resectable at presentation, and 30-40% present with borderline resectable or locally advanced/unresectable tumors. Even if resectable, the 5-year-survival rate after complete resections remains unsatisfactory, with less than 25%. This article gives an overview on current therapy standards as well as on new approaches especially for locally advanced tumors and outlines the importance of ongoing research to improve prognosis.

Could hyponatremia be a marker of anastomotic leakage after colorectal surgery? A single center analysis of 1,106 patients over 5 years.

PURPOSE: The aim of this study is to define the significance of hyponatremia as a marker of anastomotic leakage after colorectal surgery. METHODS: All anastomoses in colorectal surgery performed at a single institution between July 2007 and July 2012 (n = 1,106) were retrospectively identified. Serum sodium levels and leukocyte values measured when an anastomotic leak was diagnosed by CT scan and/or surgical reintervention (n = 81) were compared to the values preferably on postoperative day 5 in the absence of an anastomotic leak (n = 1,025). RESULTS: The leak rate in anastomoses of the rectum was 9.0 %, while the leak rate of the other anastomoses was 5.4 %. Mean serum sodium level was 138.8 mmol/l in the group with an anastomotic leak and 140.5 mmol/l in the group without. Hyponatremia (<136 mmol/l) was present in 23 % of patients in the group with an anastomotic leak and in 15 % in the group without (p < 0.001). In multivariate analysis, leukocytes and serum sodium level remained as significant markers of an anastomotic leak. As a marker of an anastomotic leak, hyponatremia had a specificity of 93 % and a sensitivity of 23 %, while the presence of either leukocytosis or hyponatremia had a sensitivity of 68 %, a specificity of 75 %, a positive predictive value of 18 %, and a negative predictive value of 97 %. CONCLUSIONS: Hyponatremia could be a specific and relevant marker of anastomotic leakage after colorectal surgery. If hyponatremia and leukocytosis are present after colorectal surgery, anastomotic leakage should be suspected and a CT scan with rectal contrast dye is recommended.

Molecular staging of lymph node-negative colon carcinomas by one-step nucleic acid amplification (OSNA) results in upstaging of a quarter of patients in a prospective, European, multicentre study.

BACKGROUND: Current histopathological staging procedures in colon carcinomas depend on midline division of the lymph nodes with one section of haematoxylin & eosin (H&E) staining only. By this method, tumour deposits outside this transection line may be missed and could lead to understaging of a high-risk group of stage UICC II cases, which recurs in ∼20% of cases. A new diagnostic semiautomated system, one-step nucleic acid amplification (OSNA), detects cytokeratin (CK) 19 mRNA in lymph node metastases and enables the investigation of the whole lymph node. The objective of this study was to assess whether histopathological pN0 patients can be upstaged to stage UICC III by OSNA. METHODS: Lymph nodes from patients who were classified as lymph node negative after standard histopathology (single (H&E) slice) were subjected to OSNA. A result revealing a CK19 mRNA copy number >250, which makes sure to detect mainly macrometastases and not isolated tumour cells (ITC) or micrometastases only, was regarded as positive for lymph node metastases based on previous threshold investigations. RESULTS: In total, 1594 pN0 lymph nodes from 103 colon carcinomas (median number of lymph nodes per patient: 14, range: 1-46) were analysed with OSNA. Out of 103 pN0 patients, 26 had OSNA-positive lymph nodes, resulting in an upstaging rate of 25.2%. Among these were 6/37 (16.2%) stage UICC I and 20/66 (30.3%) stage UICC II patients. Overall, 38 lymph nodes were OSNA positive: 19 patients had one, 3 had two, 3 had three, and 1 patient had four OSNA-positive lymph nodes. CONCLUSIONS: OSNA resulted in an upstaging of over 25% of initially histopathologically lymph node-negative patients. OSNA is a standardised, observer-independent technique, allowing the analysis of the whole lymph node. Therefore, sampling bias due to missing investigation of certain lymph node tissue can be avoided, which may lead to a more accurate staging.

Activation of the PI3K/AKT pathway correlates with prognosis in stage II colon cancer.

BACKGROUND: Patients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery. METHODS: Full-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel. RESULTS: Expression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis. CONCLUSIONS: Our data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

BACKGROUND: We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. PATIENTS AND METHODS: From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. RESULTS: Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. CONCLUSIONS: Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

Optimization of the static occlusion by "occlusal surface settling" in the Cerec 3D software.

The adjustment of the static occlusion can be automated in computer-based systems. The Cerec 3D software makes it possible to take preformed occlusal surfaces from a database and adapt them to the antagonist. In this adaptation (settling), the CAD occlusal surface "settles" as whole or each cusp individually into the occlusal surface of the antagonist until stable occlusion is reached. Two occlusal surface shapes were compared: Vita Physiodens and Lee Culp. An index was formed from the number, quality, and position of the occlusal contacts for 35 model cases (25 molars, 10 premolars). With regard to the settling of the total occlusal surfaces, there were no differences between the two occlusal surface shapes. In "cusp settling" of the molars, Vita Physiodens performed significantly better. In the comparison of the 1st with the 3rd settling process, significant improvements occurred the 3rd time in many cases when settling individual cusps, but in clearly fewer cases in the settling process of the total occlusal surface. The Lee Culp tooth occlusion improved especially after the 3rd settling process of individual cusps. It is therefore expedient to combine both settling versions with one another.

Discrimination of patients with and without vertebral fractures as measured by ultrasound and DXA osteodensitometry.

This study compares dual X-ray absorptiometry (DXA) measurements of the hip and spine with quantitative ultrasound (QUS) parameters measured simultaneously at the calcaneal and phalangeal bone in 174 patients with and without vertebral fractures. The aim of this study was to compare the ability of DXA and QUS measurements to discriminate patients with and without osteoporotic vertebral fractures and to evaluate whether QUS measurements in addition to the DXA measurements improve the clinical discrimination between patients with and without osteoporotic vertebral fractures. T-scores determined by DXA measurements at the spine and hip and QUS measurements at the calcaneus provide similar information regarding the discrimination of women with and without vertebral fractures. Phalangeal QUS measurements did not discriminate between patients with and without vertebral fractures. The discriminative power of the combined use of DXA and calcaneal QUS measurements to discern between patients with and without vertebral fractures increases in women. In contrast, the combined use of DXA and phalangeal QUS measurements resulted in decreased discriminative power as compared to DXA measurements alone. The number of fractures was higher in the quartiles with lower T-scores of the DXA and calcaneal QUS measurements whereas no difference was seen in the T-score quartiles of the phalangeal QUS device. These findings suggest that DXA and QUS measurements at weight-bearing skeletal sites provide useful information for assessing women with an anamnestic risk of osteoporotic bone loss. For DXA and calcaneal QUS measurements in men as well as for phalangeal QUS, however, a clinical algorithm remains to be established to understand the diagnostic implications and related therapeutic consequences of the obtained measurements.

[Motor behavior in depression: applications and limitations of actigraphic analyses]. / Aktivität und Depression--Möglichkeiten und Grenzen aktigraphischer Verhaltensanalysen.

OBJECTIVE: Alterations of motor behavior in depression play a key role in psychosocial activities and interpersonal communication and are relevant for differential diagnosis and treatment. Functions and application of actigraphy and empirical findings in depression will be summarised and discussed. METHODS: The current knowledge retrieved from information of manufacturers, Medline, PsycLIT, and PSYNDEX regarding features of actigraphic equipment and clinical aspects of gross motor analysis in depression was examined. RESULTS: Actigraphy is a practical method to monitor and quantify gross motor activity, but setting variables including sensitivity or epoch length vary among commercially available instruments. Measures of motor activity in depressed patients are used for diagnosis, evaluation of sleep, and prediction of treatment response. CONCLUSIONS: Measurements of motor behavior by actigraphy can be used in depression for diagnostic procedures and treatment evaluation. The role of actigraphic setting variables needs further clarification. Actigraphy may be used for behavioral analysis including individual regulation of motor activity as an objective parameter for evaluation of depression and other psychiatric disorders.

Separation anxiety and actual separation experiences during childhood in patients with panic disorder.

OBJECTIVE: The association between separation anxiety in childhood and actual separation experiences during childhood has not yet been investigated in patients with panic disorder. METHODS: In 115 patients with panic disorder with or without agoraphobia and in 124 control subjects without a history of psychiatric illness, we assessed separation anxiety during childhood, retrospectively, using DSM-IV and ICD-10 criteria and the Separation Anxiety Symptom Inventory (SASI). In addition, actual separation experiences from age 0 to 15 years were assessed, retrospectively. RESULTS: A total of 22.6% of the patients and 4.8% of the control subjects fulfilled both DSM-IV and ICD-10 criteria for childhood separation anxiety (chi 2 = 11.8; P < 0.0001). Further, 57.4% of the patients and 37.9% of the control subjects reported actual separation experiences during their childhood (chi 2 = 9.09, P < 0.003). Separation anxiety and actual separation experiences, however, were independent of each other. CONCLUSION: These results suggest that separation anxiety during childhood is not a consequence of actual traumatic separation experiences in panic disorder patients.

Contribution of glucose kinase to glucose repression of xylose utilization in Bacillus megaterium.

The glk gene from Bacillus megaterium, which encodes glucose kinase, was isolated and analyzed. Disruption by a transcriptional glk-luxAB fusion indicated that glk is the only glucose kinase gene in that strain but did not affect growth of that mutant on glucose. Determination of luciferase activity under various growth conditions revealed constitutive transcription of glk. Expression of a xylA-lacZ fusion was repressed by glucose in the strain with the glk disruption about twofold less efficiently than in the wild type. The potential contribution of glk expression to glucose repression is discussed.