Sensor Noise in LISA Pathfinder: In-Flight Performance of the Optical Test Mass Readout.

We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0_{-1.7}^{+2.4} fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.

LISA Pathfinder Performance Confirmed in an Open-Loop Configuration: Results from the Free-Fall Actuation Mode.

We report on the results of the LISA Pathfinder (LPF) free-fall mode experiment, in which the control force needed to compensate the quasistatic differential force acting on two test masses is applied intermittently as a series of "impulse" forces lasting a few seconds and separated by roughly 350 s periods of true free fall. This represents an alternative to the normal LPF mode of operation in which this balancing force is applied continuously, with the advantage that the acceleration noise during free fall is measured in the absence of the actuation force, thus eliminating associated noise and force calibration errors. The differential acceleration noise measurement presented here with the free-fall mode agrees with noise measured with the continuous actuation scheme, representing an important and independent confirmation of the LPF result. An additional measurement with larger actuation forces also shows that the technique can be used to eliminate actuation noise when this is a dominant factor.

Beyond the Required LISA Free-Fall Performance: New LISA Pathfinder Results down to 20 µHz.

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20 µHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05) fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10 fm s^{-2}/sqrt[Hz] at 20 µHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.

Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA Pathfinder.

We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.

Scoring method of a Situational Judgment Test: influence on internal consistency reliability, adverse impact and correlation with personality?

Situational Judgment Tests (SJTs) are increasingly used for medical school selection. Scoring an SJT is more complicated than scoring a knowledge test, because there are no objectively correct answers. The scoring method of an SJT may influence the construct and concurrent validity and the adverse impact with respect to non-traditional students. Previous research has compared only a small number of scoring methods and has not studied the effect of scoring method on internal consistency reliability. This study compared 28 different scoring methods for a rating SJT on internal consistency reliability, adverse impact and correlation with personality. The scoring methods varied on four aspects: the way of controlling for systematic error, and the type of reference group, distance and central tendency statistic. All scoring methods were applied to a previously validated integrity-based SJT, administered to 931 medical school applicants. Internal consistency reliability varied between .33 and .73, which is likely explained by the dependence of coefficient alpha on the total score variance. All scoring methods led to significantly higher scores for the ethnic majority than for the non-Western minorities, with effect sizes ranging from 0.48 to 0.66. Eighteen scoring methods showed a significant small positive correlation with agreeableness. Four scoring methods showed a significant small positive correlation with conscientiousness. The way of controlling for systematic error was the most influential scoring method aspect. These results suggest that the increased use of SJTs for selection into medical school must be accompanied by a thorough examination of the scoring method to be used.

[Development and Implementation of a Comprehensive Health Management System (Fit for Work and Life) for Employees of a University Hospital - A Practice Report]. / Entwicklung und Implementierung eines umfassenden Gesundheitsmanagements (Fit for Work and Life) für Mitarbeiter/innen eines Universitätsklinikums ­ ein Praxisbericht.

Background: Due to the increase of sick leave, prolonging working life and the prediction of shortage of skilled workers in the future, health management systems are continuously gaining importance. Employees in a University Hospital are exposed to particular stress factors, which are also reflected in a higher than average amount of sick leave. Against this background, the project "Fit for Work and Life" (FWL) was developed and implemented by the Hannover Medical School (MHH). Aims: FWL aims to maintain, improve or recover the work ability of employees by offering both preventive and rehabilitative treatments. A second goal is to significantly reduce the days of sick leave. Methods: The project was jointly developed and implemented by five MHH departments and the DRV Braunschweig-Hannover (DRV BS-H) according to previously defined principles. It was scientifically evaluated by the following outcomes: average days of sick leave, work ability (WAI), quality of life (SF-36, WHOQOL), coping strategies (FERUS) and effort-reward imbalance (ERI). Results and Conclusions: So far, this project is unique in its concept. It has been successfully implemented in the organisational structures of the MHH. 376 employees have registered during the first project year. Up to now, 182 participants have completed their individual programmes. The results show that 60.4% of employees have moderate to poor WAI values. The average of the mental summary scale of the SF-36 was 44.9, indicating a high workload.

Sub-Femto-g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results.

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1 fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15} g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3) fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5 mHz we observe a low-frequency tail that stays below 12 fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa.

BACKGROUND: There is a dearth of information on the precise pathogenesis of hidradenitis suppurativa (HS), but immune dysregulation is implicated. OBJECTIVES: To determine the nature of the immune response in HS. METHODS: Skin biopsies - lesional, perilesional (2 cm away) and uninvolved (10 cm away) - were obtained from patients with HS and healthy controls. The expression of various cytokines was determined by enzyme-linked immunosorbent assay, flow cytometry and real-time polymerase chain reaction. RESULTS: The expression of the inflammatory cytokines interleukin (IL)-17, IL-1ß and tumour necrosis factor-α was enhanced in lesional skin of patients with HS. In addition, IL17A and IL1B mRNA were enhanced in clinically normal perilesional skin. CD4(+) T cells produced IL-17 in HS, while CD11c(+) CD1a(-) CD14(+) cells were sources of IL-1ß. Activated caspase-1 was detected in HS skin and was associated with enhanced expression of NLRP3 and IL18. Inhibition of caspase-1 decreased IL-1ß and IL-18 production, suggesting that the caspase-1 pathway participates in IL-1ß and IL-18 expression in HS. Abnormal cytokine expression was detected in perilesional and uninvolved skin, which may suggest that subclinical inflammation is present in HS skin prior to the formation of an active lesion. CONCLUSIONS: This study demonstrates that CD4(+) T cells produce IL-17 in HS and that the IL-17 pathway may be important in HS pathogenesis. CD11c(+) CD1a(-) CD14(+) cells are a source of IL-1ß in HS, the production of which was shown to be mediated, in part, via a caspase-1-dependent pathway. These results suggest that IL-17 and the caspase-1-associated cytokines IL-1ß and IL-18 may play a role in the pathogenesis of HS.

[Is the Intrahepatic Sound Speed an Indicator of the Fat Content of the Liver in Children?]. / Die intrahepatische Schallgeschwindigkeit als möglicher Parameter zur Abschätzung der Steatosis hepatis bei Kindern?

PURPOSE: Can the sonographically estimated intrahepatic sound speed give hints on the hepatic fat content in children? MATERIALS AND METHODS: In 75 children and adolescents the intrahepatic sound speed was estimated during routine sonography of the liver as a result of an image reconstruction algorithm. It was correlated with weight, age, size, and body mass index (BMI) oft he children, respectively. RESULTS: The average hepatic sound speed in children of normal weight was 1 566 m/s (standard deviation (STD) 29 m/s, in overweight or obese children it was 1 501 m/s (STD 22 m/s), and in obese children it was 1 497 ms (STD 24 m/s). The strongest correlation was found between sound speed and BMI of the children, respectively. The difference of sound speed in normal weighing subjects and overweight/obese children was statistically significant. CONCLUSION: There is a good correlation between the estimated intrahepatic sound speed and the fat content of the liver. Further examinations are encouraged.

[Study of the psychometric properties of the CES-D in a sample of French-speaking adolescents]. / Étude des propriétés psychométriques de l'échelle CES-D sur un échantillon d'adolescents francophones scolarisés.

UNLABELLED: The aim of this paper is to study and validate the French version of the Center for Epidemiologic Studies Depression Scale developed by Radloff (in 1977) in an adolescent sample. This scale was developed to measure levels of depressive symptomatology, with special emphasis on the affective components and depressed mood. METHOD: The data used in this study were collected in 11 schools. Our sample was composed of 1496 French-speaking, Belgian secondary school students aged 12 to 16 years. The questionnaire included demographic information such as age, gender, grade and family composition. The position of the CES-D scale has not changed and was placed in the last part of the self-administered questionnaire. RESULTS: After an exploratory factor analysis, we conducted confirmatory factor analysis to test our factor model. We tested the model with four factors proposed by Radloff (in 1977) and also the model proposed by Chabrol (in 2002). Our results indicate a better match with Radloff's model in our sample, showing the relevance of using Radloff's model with four factors in adolescents. Although our analysis shows a clear gender difference with regard to depressive symptoms, the tested factor model remained stable regardless of the gender of the adolescent.

Confined placental mosaicism: Distribution of chromosomally abnormal cells over the term placenta.

OBJECTIVE: Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. METHODS: Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. RESULTS: The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. DISCUSSION: Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.

A premature termination mutation in a patient with Lowe syndrome without congenital cataracts: dropping the "O" in OCRL.

The oculocerebrorenal syndrome of Lowe is an X-linked recessive disorder characterized by the triad of congenital cataracts, mental retardation and a renal proximal tubulopathy. Although severity of phenotype might vary, congenital cataracts are part of the definition of this rare disorder.We report a 13-year-old patient with the typical cerebrorenal phenotype of Lowe syndrome, that had remained undiagnosed due to absence of any ocular involvement. OCRL gene analysis was carried.DNA analysis revealed a c.C760T (p.Gln199X) nonsense mutation in exon 8 expected to cause complete disruption of OCRL function. After sequencing the parents of the index patient and his maternal grandparents, this mutation turned out to be de novo in the mother. Furthermore, a silent variant (p.Arg35=) was identified in exon 2, that could also be identified in the mother and her 3 sisters, but not in the grandparents assuming germ cell mosaicism in either of the grandparents. RNA analysis from the patient's lymphocytes revealed presence of full-length OCRL transcripts. Western blotting from lymphocyte samples failed to detect OCRL protein even in controls.Our findings extend the phenotypic spectrum caused by OCRL mutations and illustrate that there may be selective organ involvement in Lowe syndrome.

[Transient splenial lesion in influenza A H1N1 2009 infection]. / Transiente Spleniumläsion bei Influenza-A-H1N1-09-Infektion.

Severe neurologic complications have been rarely reported during novel pandemic influenza A(H1N1) virus infections. We describe the case of an 10-year-old boy with new onset seizures and proven influenza A(H1N1) 2009 infection showing a reversible hyperintense lesion in the splenium of the corpus callosum on T2-weighted and FLAIR magnetic resonance images without contrast enhancement. Transient splenial lesions have been described in the context of virus encephalopathy and do not require specific treatment.

[Cerebral MRI of preterm neonates at term equivalent age at 3 Tesla: hints at white matter damage on T2- and diffusion weighted images]. / Erfahrungen mit der MRT des Hirns bei Frühgeborenen--Hinweise auf Schädigung der weißen Substanz in T2- und Diffusionswichtung bei 3 Tesla.

BACKGROUND: MRI of the brain is reported to be very sensitive in the detection of diffuse white matter damage in preterm neonates. AIM: To review 3 Tesla-MRI studies of 21 preterm neonates at term equivalent age with regard to safety and detection of white matter changes. PATIENTS: In 21 preterm neonates (9 female, 12 male, mean age 96 days) an MRI of the brain was performed for clinical reasons with oral sedation. All examinations could be performed at 3 Tesla without any complication. In 7 of 21 noncystic periventricular white matter lesions could be found and in 14 hyperintensity of white matter (DEHSI) was observed. ADC-values of the white matter were considerably higher than reported for healthy children in literature. CONCLUSION: MRI at 3 Tesla can be performed safely in oral sedation at term equivalent age at 3 Tesla. T2-weighted and diffusion-weighted imaging is very sensitive for white matter changes.

Renal cell carcinoma with Xp11.2 translocation in a 7-year-old boy.

BACKGROUND: More than 90% of pediatric renal tumors are nephroblastomas while renal cell carcinomas (RCC) are rare in children (< 5%). PATIENT: According to the clinical diagnoses of a nephroblastoma stage IV a 7-year-old boy with a kidney tumor and peripheral pulmonary lesion was preoperatively treated for 8 weeks with Vincristine, Actinomycin D and Adriamycin. The resected kidney displayed a RCC with Xp11.2 translocation. There was no tumor regression and the pulmonary lesion was no longer detectable. Hence chemotherapy was put to a halt. CONCLUSION: Fine needle aspiration biopsy (FNA) would have allowed to adjust the tumor subtype. Prognosis of pediatric RCC with translocation seems more favourable than without translocation though definitive evidence will only be possible by documentation in a clinical diagnose-related register.

Aortobifemoral embolism in an 18-year old patient following cisplatin and 5-fluorouracil chemotherapy for nasopharyngeal carcinoma.

After cisplatin / 5-fluorouracil chemotherapy for nasopharyngeal carcinoma, an 18-year female patient developed aortobifemoral embolism. Besides chemotherapy, additional risk factors for arterial thromboembolic events were smoking, contraceptive medication and adjuvant antiemetic treatment with dexamethasone. Thrombophilia screening was negative. Thromboembolic complications during or after cisplatin have been reported in a frequency of 17.6 % in lung cancer patients, and in 8.4 % of patients with germ cell tumors. The incidence of arterial thromboembolic events was 9.3 % and 1.7 %, respectively. The pathogenesis of cisplatin induced thromboembolism is thought to be caused by endothelial damage leading to endothelial cell dysfunction, increased von Willebrand factor plasma levels, and hypomagnesaemia.

Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder.

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data.

[Current stage of fMRI applications in newborns and children during the first year of life]. / Gegenwärtiger Stand der funktionellen MRT bei Neugeborenen und Kindern im ersten Lebensjahr.

Currently, a paradigm shift towards expanded early use of cranial MRI in newborns at risk and infants in the first year of life can be observed in neonatology. Beyond clinical MRI applications, there is progressive use of functional MRI (fMRI) in this age group. On the one hand, fMRI allows monitoring of functional developmental processes depending on maturational stage; on the other hand, this technique may provide the basis for early detection of pathophysiological processes as a prerequisite for functionally guided therapeutic interventions. This article provides a comprehensive review of current fMRI applications in neonates and infants during the first year of life and focuses on the associated methodological issues (e. g. signal physiology, sedation, safety aspects).

Visible Blue Light Therapy: Molecular Mechanisms and Therapeutic Opportunities.

BACKGROUND: Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near infrared regions of the visible spectrum. Considerably less effort has been dedicated to the blue, UV-free part of the spectrum. OBJECTIVE: In this review, we discuss the current advances in the understanding of the molecular photoacceptors, signaling mechanisms, and corresponding therapeutic opportunities of blue light photoreception in non-visual mammalian cells in the context of inflammatory skin conditions. METHODS: The literature was scanned for peer-reviewed articles focusing on the molecular mechanisms, cellular effects, and therapeutic applications of blue light. RESULTS: At a molecular level, blue light is absorbed by flavins, porphyrins, nitrosated proteins, and opsins; inducing the generation of ROS, nitric oxide release, and the activation of G protein coupled signaling. Limited and contrasting results have been reported on the cellular effects of blue light induced signaling. Some investigations describe a regulation of proliferation and differentiation or a modulation of inflammatory parameters; others show growth inhibition and apoptosis. Regardless of the elusive underlying mechanism, clinical studies show that blue light is beneficial in the treatment of inflammatory skin conditions. CONCLUSION: To strengthen the use of blue light for therapeutic purposes, further in depth studies are clearly needed with regard to its underlying molecular and cellular mechanisms, and their translation into clinical applications.