Nuclear Charge Radius of

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

Collinear Laser Spectroscopy of 2

Transition frequencies and fine-structure splittings of the 2 ^{3}S_{1}→2 ^{3}P_{J} transitions in helium-like ^{12}C^{4+} were measured by collinear laser spectroscopy on a 1-ppb level. Accuracy is increased by more than 3 orders of magnitude with respect to previous measurements, enabling tests of recent nonrelativistic (NR) QED calculations including terms up to mα^{7}. Deviations between the theoretical and experimental values are within theoretical uncertainties and are ascribed to mα^{8} and higher-order contributions in the series expansion of the NR QED calculations. Finally, prospects for an all-optical charge radius determination of light isotopes are evaluated.

[How to handle unkown fluids in fluid-preserved collections : Cloudy prospects?] / Zum Umgang mit Präparaten in unbekannten Konservierungslösungen in Feuchtpräparatesammlungen : Trübe Aussichten?

BACKGROUND: Fluid collections are gaining more importance for research and teaching, but they are facing preservation problems. In the case of historical collections, the methods of fixation and preservation are poorly documented. The liquid used is unknown. In order to ensure the preservation of such collections, it is essential to have available a preservation liquid that is compatible with the most common historical liquids and techniques. MATERIALS AND METHODS: A universal liquid based on historical recipes was developed for such problematic preparations. RESULTS: The use of distilled water, glycerin and ethanol (80%) in a ratio of 10:6:1 offers a good alternative that is harmless to the health of the user. It can be used for colour-preserving conserved preparations and for pure ethanol and formaldehyde preparations and is recommended as a universal solution for preparations in unknown preservation liquids.

A new Collinear Apparatus for Laser Spectroscopy and Applied Science (COALA).

We present a new collinear laser spectroscopy setup that has been designed to overcome systematic uncertainty limits arising from high-voltage and frequency measurements, beam superposition, and collisions with residual gas that are present in other installations utilizing this technique. The applied methods and experimental realizations are described, including an active stabilization of the ion-source potential, new types of ion sources that have not been used for collinear laser spectroscopy so far, dedicated installations for pump-and-probe measurements, and a versatile laser system referenced to a frequency comb. The advanced setup enables us to routinely determine transition frequencies, which was so far demonstrated only for a few cases and with lower accuracy at other facilities. It has also been designed to perform accurate high-voltage measurements for metrological applications. Demonstration and performance measurements were carried out with Ca+ and In+ ions.

Non-invasive evaluation of human mucosal structures by multiphoton laser scanning tomography in vitro.

BACKGROUND: Mucous membranes may be affected by various diseases and the diagnostic accessibility is limited. Multiphoton laser tomography (MPT) is a useful tool for in vivo evaluation of superficial skin structures and might also be useful for the imaging of mucosa. OBJECTIVES: In order to investigate the suitability of MPT for the evaluation of mucous membranes, tissue samples of different donors and anatomical localizations have been imaged. METHODS: Human mucosa samples from the urinary bladder, palatine tonsil and ocular conjunctiva were investigated by MPT and subsequently compared with conventional histology. RESULTS: Horizontal images of the epithelium and the underlying connective tissue were obtained using the autofluorescence and second harmonics generation signals by MPT. The stratification of multilayered epithelium was consistently reproduced. Also inflammatory changes like lymphocytic infiltrates and widened intercellular spaces were imaged in some cases. CONCLUSION: Mucous tissue samples were obtained and MPT imaging was successfully performed. In the direct comparison with histology of the same tissue samples, the characteristic morphology of the epithelia was found. Further studies are necessary in order to compare images of healthy and diseased mucosal epithelium and the use of MPT for its evaluation in vivo.

Impact of refractive index mismatches on coherent anti-Stokes Raman scattering and multiphoton autofluorescence tomography of human skin in vivo.

Optical non-linear multimodal tomography is a powerful diagnostic imaging tool to analyse human skin based on its autofluorescence and second-harmonic generation signals. Recently, the field of clinical non-linear imaging has been extended by adding coherent anti-Stokes Raman scattering (CARS)-a further optical sectioning method for the detection of non-fluorescent molecules. However, the heterogeneity of refractive indices of different substances in complex tissues like human skin can have a strong influence on CARS image formation and requires careful clinical interpretation of the detected signals. Interestingly, very regular patterns are present in the CARS images, which have no correspondence to the morphology revealed by autofluorescence at the same depth. The purpose of this paper is to clarify this phenomenon and to sensitize users for possible artefacts. A further part of this paper is the detailed comparison of CARS and autofluorescence images of healthy human skin in vivo covering the complete epidermis and part of the upper dermis by employing the flexible medical non-linear tomograph MPTflex CARS.

Experienced and inexperienced observers achieved relatively high within-observer agreement on video mobility scoring of dairy cows.

Assessment of lameness prevalence and severity requires visual evaluation of thelocomotion of a cow. Welfare schemes including locomotion assessments are increasingly being adopted, and more farmers and their veterinarians might implement a locomotion-scoring routine together. However, high within-observer agreement is a prerequisite for obtaining valid mobility scorings, and within-observer agreement cannot be estimated in a barn, because the gait of cows is dynamic and may change between 2 occasions. The objective of this study was to estimate the within-observer agreement according to the observers' educational background and experience with cattle, based on video recordings with very diverse types of gait. Groups of farmers, bovine veterinarians, first- and fourth-year veterinary students, researchers, and cattle-inexperienced sensory assessors evaluated mobility using a 5-point mobility score system developed specifically for walking cows (n=102 observers). The evaluation sessions were similar for all groups, lasted 75 min, and were organized as follows: introduction, test A, short training session, break, and test B. In total, video recordings of 22 cows were displayed twice in a random order (11 cows in each test × 2 replicates). Data were analyzed applying kappa coefficient, logistic regression, and testing for random effects of observers. The crude estimates of 95% confidence interval for weighted kappa in test A and B ranged, respectively, from 0.76 to 0.80 and 0.70 to 0.75. When adjusting for the fixed effects of video sample and gait scoring preferences, the probability of assigning the same mobility score twice to the same cow varied from 55% (sensory assessors) to 72% (fourth-year veterinary students). The random effect of the individual observers was negligible. That is, in general observers could categorize the mobility characteristics of cows quite well. Observers who preferred to assess the attributes back arch or the overall mobility score (based on uneven gait) had the highest agreement, respectively, 69 or 68%. The training session seemed insufficient to improve agreement. Nonetheless, even novice observers were able to achieve perfect agreement up to 60% of the 22 scorings with merely the experience obtained during the study (introduction and training session). The relatively small differences between groups, together with a high agreement, demonstrate that the new system is easy to follow compared with previously described scoring systems. The mobility score achieves sufficiently high within-observer repeatability to allow between-observer agreement estimates, which are reliable compared with other more-complex scoring systems. Consequently, the new scoring scale seems feasible for on-farm applications as a tool to monitor mobility within and between cows, for communication between farmers and veterinarians with diverse educational background, and for lamenessbenchmarking of herds.

Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data: Successful Model of Intersectoral Communication for Quality Assurance.

Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment.

The relationship between BNP, NTproBNP and echocardiographic measurements of systemic blood flow in very preterm infants.

OBJECTIVE: Preterm infants are at risk of circulatory compromise following birth. Functional neonatal echocardiography including superior vena cava (SVC) flow is increasingly used in neonatal medicine, and low SVC flow has been associated with adverse outcome. However, echocardiography is not readily available in many neonatal units and B-type natriuretic peptides (BNPs) may be useful in guiding further cardiovascular assessment. This study investigated the relationship between BNP, N-terminal pro-BNP (NTproBNP) and echocardiographic measurements of systemic blood flow in very preterm infants. STUDY DESIGN: This is a prospective observational study. Sixty preterm infants <32 weeks gestational age were included after the treating neonatologist had requested an echocardiogram for suspected cardiovascular compromise. BNP and NTproBNP were sampled just before the echocardiogram. Echocardiographic examination included fractional shortening (FS), SVC flow, left and right ventricular output (LVO and RVO). Statistical analysis included simple linear regression of BNP and NTproBNP with echocardiographic measures and multiple regression including potential confounding variables. RESULT: Mean (s.d.) gestational age at birth was 27(5) (2(1)) weeks, median (interquartile range, IQR) birth weight was 995 (845 to 1175) grams. Neither BNP nor NTproBNP correlated with SVC flow (BNP 95% confidence interval (CI) -0.0014 to 0.013, P=0.12; NTproBNP 95% CI -0.00069 to 0.01, P=0.085); LVO (BNP 95% CI -0.00078 to 0.0072, P=0.11; NTproBNP 95% CI -0.0034 to 0.0034, P=0.99); RVO (BNP 95% CI -0.00066 to 0.0058, P=0.12; NTproBNP 95% CI -0.0012 to 0.0044, P=0.25); or FS (BNP 95% CI -0.053 to 0.051, P=0.96; NTproBNP 95% CI -0.061 to 0.019, P=0.3). Multivariate linear regression did not significantly alter results. CONCLUSION: In this cohort of very preterm infants, BNP and NTproBNP did not correlate with echocardiographic measurements of systemic blood flow within the first 72 h of life.

COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy.

BACKGROUND: This prospective study evaluated the relationship between arthralgia and compliance during the first year of adjuvant anastrozole therapy in postmenopausal women with hormone receptor-positive early breast cancer. PATIENTS AND METHODS: COMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open-label, multicenter, noninterventional study conducted in Germany. Patients had started adjuvant anastrozole 3-6 months before the study start. The primary end points were arthralgia, compliance, and the relationship between compliance and arthralgia, assessed at specific time points. RESULTS: Overall, 1916 patients received upfront anastrozole. Mean arthralgia scores were increased from baseline at each visit up to 9 months. Compliance with anastrozole therapy gradually decreased over time from baseline to 9 months (P<0.001). At 9 months, investigators estimated that >95% of patients were compliant versus patient reports of <70%. There was a significant association between arthralgia mean scores and noncompliance at 6 months (P<0.0001), 9 months (P<0.0001), and overall (P<0.0001). Over time, new events or impairment of existing arthralgias were reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients. CONCLUSION: Arthralgia is important in the clinical management of women with early breast cancer and may contribute to noncompliance and clinical outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT00857012.

Crucial role of Plexin C1 for pulmonary inflammation and survival during lung injury.

Acute pulmonary inflammation during lung injury is initiated by the migration of neutrophils into the alveolar space. The severity of these inflammatory changes within the pulmonary tissue determines the severity of lung injury and ultimately patient outcome. Recent work has demonstrated that the guidance protein Semaphorin 7A propagates the infiltration of neutrophils into an hypoxic tissue site, yet the role of its target receptor Plexin C1 (PLXNC1) during lung injury is to date unknown. We demonstrate here that PLXNC1(+) neutrophils are present within the alveolar space and that PLXNC1 is induced in vitro and in vivo during lung injury. In a model of high-pressure ventilation PLXNC1(-/-) animals show decreased signs of alveolar inflammation and improved survival compared with wild-type controls. Studies employing chimeric animals identified the hematopoietic expression of PLXNC1 to be of crucial importance for the observed results. Functional inhibition of PLXNC1 resulted in improved survival and ameliorated the signs of inflammation within the lung. Furthermore, the injection of a peptide binding to PLXNC1 resulted in improved survival and attenuated pulmonary inflammation. As such we demonstrate here, that previously unknown PLXNC1 holds significant importance for degree of pulmonary inflammation and determines outcome during experimental lung injury.

[Google translate is not sufficient to overcome language barriers in neonatal medicine]. / Erste Erfahrungen mit Google Translate in der Neonatologie.

Language barriers hinder the interaction with patients and relatives. The use of language services increases knowledge, satisfaction and the use of medical care and thus improves patient's clinical outcome. The recommended use of professional interpreters (PI) is not always feasible. We tested an online translation tool as an alternative for PI for the transla-tion of standardized sentences from a neonatal doctor-/nurse-relative-interview.Translation of 20 sentences from a German neonatal intensive care unit parent information brochure to English, Portuguese and Arabic, using Google Translate (GT). Assessment of accuracy concerning grammar and content, in a second step simplification of all incorrect sentences, translation by GT and critical re-assessment and evaluation.An average of 42% of the sentences was correctly translated concerning grammar and content. The proportion of incorrectly translated sentences varied between 45-70%. By simpli-fication another 23% were translated correctly.Translations by GT were often incorrect in content and grammar. We suppose that the design of GT, which is a statistical translation engine, might be an explanation for this phenomenon. Presently, GT cannot guarantee unambiguous translations and cannot substitute PIs, only in particular circumstances, the use of GT or similar engines may be justified. For future use of electronic translation services, we suggest to compile a catalogue of sentences containing central information, which can be translated into defined foreign languages without misinterpretation or loss of information.

[Molecular pathology of the lungs. New perspectives by next generation sequencing]. / Molekularpathologie der Lunge. Perspektiven durch neue Sequenzierformen.

Lung cancer is one of the most frequent malignancies in the western world. Its frequent association with a wide spectrum of mutations in genes encoding various signal transducers that are often linked to therapy response, emphasizes the obvious need for improved, fast and highly efficient approaches in molecular pathology. Comprehensive analyses of the mutation status of progression and therapy relevant genes can be performed by the novel sequencing forms named next generation sequencing (NGS) providing extremely high capacities for ultra-deep sequence analyses. The 454 pyrosequencing method, the sequencing by synthesis and the semiconductor sequencing platform are now available for parallel sequencing approaches of multitudinous target genes linked to multiple tumor DNA applications. The "one molecule, one clone, one read" principle by the NGS approaches supplies not only information on allele frequencies and mutation rates but also has the advantage of a very sensitive detection of low frequency variants.

The effect of sildenafil on retinopathy of prematurity in very preterm infants.

OBJECTIVE: Sildenafil is occasionally used as rescue treatment for preterm infants with severe bronchopulmonary dysplasia and pulmonary arterial hypertension. In adults, sildenafil treatment has been associated with several ophthalmological adverse effects, including nonarteritic ischaemic optic neuropathy. We reviewed the effect of sildenafil on retinopathy of prematurity (ROP) in very preterm infants. STUDY DESIGN: Retrospective case-control study. Infants born <30 weeks gestation who had received sildenafil during their hospitalisation were included. A control group matched for gestation, birth weight, gender, and place of birth was identified from the departmental database. For every sildenafil case, three matched controls were studied. Baseline data, sildenafil therapy data, results of eye examinations and respiratory data were analysed. RESULT: 17 infants received sildenafil between 2004 and 2010. The median duration of sildenafil treatment was 52 days. Baseline characteristics were similar between groups. The odds ratio for an increase in ROP stage in the group treated with sildenafil was 1.35 (95% confidence interval 0.39-4.62, P-value 0.63). One infant in each group required laser treatment. CONCLUSION: Sildenafil treatment did not affect ROP progression or increase the need for laser treatment in this cohort.

Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation.

Lysine (K)-specific demethylase 1A (LSD1/KDM1A) has been identified as a potential therapeutic target in solid cancers and more recently in acute myeloid leukemia. However, the potential side effects of a LSD1-inhibitory therapy remain elusive. Here, we show, with a newly established conditional in vivo knockdown model, that LSD1 represents a central regulator of hematopoietic stem and progenitor cells. LSD1 knockdown (LSD1-kd) expanded progenitor numbers by enhancing their proliferative behavior. LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors. In contrast, terminal granulopoiesis, erythropoiesis and platelet production were severely inhibited. The only exception was monopoiesis, which was promoted by LSD1 deficiency. Importantly, we showed that peripheral blood granulocytopenia, monocytosis, anemia and thrombocytopenia were reversible after LSD1-kd termination. Extramedullary splenic hematopoiesis contributed to the phenotypic reversion, and progenitor populations remained expanded. LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, Hoxa9 and Meis1, which are known regulators of the HSC/progenitor compartment. We also demonstrated that LSD1-kd abrogated Gfi1b-negative autoregulation by crossing LSD1-kd with Gfi1b:GFP mice. Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.

Safety assessment by multiphoton fluorescence/second harmonic generation/hyper-Rayleigh scattering tomography of ZnO nanoparticles used in cosmetic products.

Zinc oxide nanoparticles (ZnO NPs) are commonly used as UV filters in commercial sunscreen products. Their penetration into the skin is intensively discussed in the literature. In the present in vivo study, penetration of ZnO NPs (30 nm in size) into human skin was investigated by multiphoton tomography. Based on the non-linear effects of a second harmonic generation and hyper-Rayleigh scattering, the distribution of ZnO NPs in the horny layers of the epidermis, as well as the furrows, wrinkles and orifice of the hair follicles was analyzed. This method permitted distinguishing between the particulate and dissolved forms of Zn. A detection limit of 0.08 fg/µm(3) was estimated. Taking advantage of this sensitivity, it was clearly shown that ZnO NPs penetrate only into the outermost layers of stratum corneum, furrows and into the orifices of the hair follicles and do not reach the viable epidermis.

[Experimental corneal imaging and corneal surgery with non-amplified femtosecond laser pulses]. / Experimentelle Hornhautbildgebung und Hornhautchirurgie mit nicht verstärkten Femtosekundenlaserpulsen.

BACKGROUND: Non-amplified femtosecond laser was used to induce multiphoton effects for corneal tissue imaging and for tissue ablation. MATERIAL AND METHODS: A non-amplified titanium-sapphire laser was coupled to a laser scanning microscope in order to examine human and porcine cornea. Tissue was subjected to imaging and lesions were created using identical optical pathways at pulse energies below 2 nJ. RESULTS: Cellular components and the extracellular matrix were selectively imaged by applying autofluorescence and second harmonic generation at submicron resolution. Intrastromal linear scanning at higher power resulted in luminescent plasma along the scanning line. Lesion width decreased with increasing tissue depth and increased with increasing laser power at the target. Light microscopy showed intact stromal tissue around the area of the lesion. CONCLUSIONS: High-resolution images as well as high precision tissue lesions were created in the cornea using low energy femtosecond laser pulses. Easy switching between tissue imaging and ablation seems to be suitable for diagnostic and therapeutic applications.