Congenital adrenal hyperplasia

Congenital adrenal hyperplasia consists of a heterogenous group of inherited disorders due to enzymatic defects in the biosynthetic pathway of cortisol and/or aldosterone. This results in glucocorticoid deficiency, mineralocorticoid deficiency, and androgen excess. 95% of CAH cases are due to 21-hydroxylase deficiency. Clinical forms range from the severe, classical CAH associated with complete loss of enzyme function, to milder, non-classical forms (NCAH). Androgen excess affects the pilosebaceous unit, causing cutaneous manifestations such as acne, androgenetic alopecia and hirsutism. Clinical differential diagnosis between NCAH and polycystic ovary syndrome may be difficult. In this review, the evaluation of patients with suspected CAH, the clinical presentation of CAH forms, with emphasis on the cutaneous manifestations of the disease, and available treatment options, will be discussed

Visualizing dimensionality reduction of systems biology data

One of the challenges in analyzing high-dimensional expression data is the detection of important biological signals. A common approach is to apply a dimension reduction method, such as principal component analysis. Typically, after application of such a method the data is projected and visualized in the new coordinate system, using scatter plots or profile plots. These methods provide good results if the data have certain properties which become visible in the new coordinate system and which were hard to detect in the original coordinate system. Often however, the application of only one method does not suffice to capture all important signals. Therefore several methods addressing different aspects of the data need to be applied. We have developed a framework for linear and non-linear dimension reduction methods within our visual analytics pipeline SpRay. This includes measures that assist the interpretation of the factorization result. Different visualizations of these measures can be combined with functional annotations that support the interpretation of the results. We show an application to high-resolution time series microarray data in the antibiotic-producing organism Streptomyces coelicolor as well as to microarray data measuring expression of cells with normal karyotype and cells with trisomies of human chromosomes 13 and 21

Orbital superfluidity in the PP-band of a bipartite optical square lattice

The successful emulation of the Hubbard model in optical lattices has stimulated world wide efforts to extend their scope to also capture more complex, incompletely understood scenarios of many-body physics. Unfortunately, for bosons, Feynmans fundamental "no-node" theorem under very general circumstances predicts a positive definite ground state wave function with limited relevance for many-body systems of interest. A promising way around Feynmans statement is to consider higher bands in optical lattices with more than one dimension, where the orbital degree of freedom with its intrinsic anisotropy due to multiple orbital orientations gives rise to a structural diversity, highly relevant, for example, in the area of strongly correlated electronic matter. In homogeneous two-dimensional optical lattices, lifetimes of excited bands on the order of a hundred milliseconds are possible but the tunneling dynamics appears not to support cross-dimensional coherence. Here we report the first observation of a superfluid in the $P$-band of a bipartite optical square lattice with $S$-orbits and $P$-orbits arranged in a chequerboard pattern. This permits us to establish full cross-dimensional coherence with a life-time of several ten milliseconds. Depending on a small adjustable anisotropy of the lattice, we can realize real-valued striped superfluid order parameters with different orientations $P_x \pm P_y$ or a complex-valued $P_x \pm i P_y$ order parameter, which breaks time reversal symmetry and resembles the $\pi$-flux model proposed in the context of high temperature superconductors. Our experiment opens up the realms of orbital superfluids to investigations with optical lattice models.Comment: 5 pages, 5 figure

Persistent fluctuations in stride intervals under fractal auditory stimulation

Copyright @ 2014 Marmelat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.Commission of the European Community and the Netherlands Organisation for Scientific Research

Bridge-specific fragility analysis: when is it really necessary?

In seismic assessment of bridges the research focus has recently shifted on the derivation of bridge-specific fragility curves that account for the effect of different geometry, structural system, component and soil properties, on the seismic behaviour. In this context, a new, component-based methodology for the derivation of bridge-specific fragility curves has been recently proposed by the authors, with a view to overcoming the inherent difficulties in assessing all bridges of a road network and the drawbacks of existing methodologies, which use the same group of fragility curves for bridges within the same typological class. The main objective of this paper is to critically assess the necessity of bridge-specific fragility analysis, starting from the effect of structure-specific parameters on component capacity (limit state thresholds), seismic demand, and fragility curves. The aforementioned methodology is used to derive fragility curves for all bridges within an actual road network, with a view to investigating the consistency of adopting generic fragility curves for bridges that fall within the same class and quantifying the degree of over- or under-estimation of the probability of damage when generic bridge classes are considered. Moreover, fragility curves for all representative bridges of the analysed concrete bridge classes are presented to illustrate the differentiation in bridge fragility for varying structural systems, bridge geometry, total bridge length and maximum pier height. Based on the above, the relevance of bridge-specific fragility analysis is assessed, and pertinent conclusions are drawn

Community-acquired MRSA and pig-farming

BACKGROUND: Sporadic cases of CA-MRSA in persons without risk-factors for MRSA carriage are increasing. CASE PRESENTATION: We report a MRSA cluster among family members of a pig-farmer, his co-workers and his pigs. Initially a young mother was seen with mastitis due to MRSA. Six months later her baby daughter was admitted to the hospital with pneumococcal otitis. After staying five days in hospital, the baby was found to be MRSA positive. At that point it was decided to look for a possible source, such as other family members and house-hold animals, including pigs on the farm, since those were reported as a possible source of MRSA earlier. Swabs were taken from the throat and nares of family members and co-workers. A veterinarian obtained swabs from the nares, throat and perineum of 10 pigs. Swabs were cultured following a national protocol to detect MRSA that included the use of an enrichment broth. Animal and human strains were characterized by PFGE, spa-typing, MLST analysis, SSCmec, AGR typing, and the detection for PVL, LukM, and TSST toxin genes. Three family members, three co-workers, and 8 of the 10 pigs were MRSA positive. With the exception of the initial case (the mother) all persons were solely colonized, with no signs of clinical infections. After digestion with SmaI, none of the strains showed any bands using PFGE. All isolates belonged to spa type t108 and ST398. CONCLUSION: 1. This report clearly shows clonal spread and transmission between humans and pigs in the Netherlands. 2. MLST sequence type 398 might be of international importance as pig-MRSA, since this type was shown earlier to be present in epidemiologically unrelated French pigs and pig-farmers. 3. Research is needed to evaluate whether this is a local problem or a new source of MRSA, that puts the until now successful Search and Destroy policy of the Netherlands at risk

Trauma induces apoptosis in human thoracolumbar intervertebral discs

BACKGROUND: Vertebral fractures resulting from high energy trauma often comprise the risk of posttraumatic degenerative changes in the affected intervertebral discs (IVD). Particularly in conservatively treated patients, or in cases after implant removal of an exclusively posterior stabilization, consecutive disc degeneration and the associated functional losing of the spinal segment clearly represent detrimental treatment results. In this regard, apoptosis of IVD cells has been suggested to be involved in the critical changes of the extracellular matrix. METHODS: To investigate whether fractures of the vertebrae induce apoptosis in the affected IVD, disc tissue from patients (n = 17) undergoing open reduction and internal fixation of thoracolumbar spine fractures were analysed in regards to caspase activity, apoptosis-receptor expression levels and gene expression of apoptosis-regulating proteins such as Bax and Bcl-2. Healthy IVD tissue (n = 3) obtained from patients undergoing surgical resection of adjacent vertebrae were used as control samples. RESULTS: In contrast to healthy control IVD tissues, samples from traumatic thoracolumbar IVD showed positive TUNEL staining and a significant increase of caspase-3/7 activity. Interestingly, analyses of the initiator caspase-8 and -9 revealed significantly increased activation levels compared to control values, suggesting the coexistent activation of both the extrinsic (receptor-mediated) and intrinsic (mitochondria-mediated) apoptosis pathway. Accordingly, expression levels of the Fas receptor (FasR) mRNA were significantly increased. Although the TNF receptor I (TNFR I) was only slightly upregulated, corresponding TNFα from trauma IVD presented significantly increased mRNA expression values. Furthermore, traumatic IVD cells demonstrated significantly reduced expression of the mitochondria-bound anti-apoptotic Bcl-2, thereby maintaining baseline transcriptional levels of the pro-apoptotic Bax protein when compared to control IVD cells. CONCLUSION: Our data suggest that thoracolumbar fractures induce early caspase-dependent apoptosis in IVD cells of the affected intervertebral disc, in part, by downregulation of the anti-apoptotic protein Bcl-2 (intrinsic apoptosis pathway), as well as signalling via the death receptor complex (TNFR I and FasR)

Proximity to Sports Facilities and Sports Participation for Adolescents in Germany

Objectives - To assess the relationship between proximity to specific sports facilities and participation in the corresponding sports activities for adolescents in Germany. Methods - A sample of 1,768 adolescents aged 11–17 years old and living in 161 German communities was examined. Distances to the nearest sports facilities were calculated as an indicator of proximity to sports facilities using Geographic Information Systems (GIS). Participation in specific leisure-time sports activities in sports clubs was assessed using a self-report questionnaire and individual-level socio-demographic variables were derived from a parent questionnaire. Community-level socio-demographics as covariates were selected from the INKAR database, in particular from indicators and maps on land development. Logistic regression analyses were conducted to examine associations between proximity to the nearest sports facilities and participation in the corresponding sports activities. Results - The logisitic regression analyses showed that girls residing longer distances from the nearest gym were less likely to engage in indoor sports activities; a significant interaction between distances to gyms and level of urbanization was identified. Decomposition of the interaction term showed that for adolescent girls living in rural areas participation in indoor sports activities was positively associated with gym proximity. Proximity to tennis courts and indoor pools was not associated with participation in tennis or water sports, respectively. Conclusions - Improved proximity to gyms is likely to be more important for female adolescents living in rural areas

Ultrafast hole carrier relaxation dynamics in p-type CuO nanowires

Ultrafast hole carrier relaxation dynamics in CuO nanowires have been investigated using transient absorption spectroscopy. Following femtosecond pulse excitation in a non-collinear pump-probe configuration, a combination of non-degenerate transmission and reflection measurements reveal initial ultrafast state filling dynamics independent of the probing photon energy. This behavior is attributed to the occupation of states by photo-generated carriers in the intrinsic hole region of the p-type CuO nanowires located near the top of the valence band. Intensity measurements indicate an upper fluence threshold of 40 μJ/cm2 where carrier relaxation is mainly governed by the hole dynamics. The fast relaxation of the photo-generated carriers was determined to follow a double exponential decay with time constants of 0.4 ps and 2.1 ps. Furthermore, time-correlated single photon counting measurements provide evidence of three exponential relaxation channels on the nanosecond timescale

A new concept for the combination of optical interferometers and high-resolution spectrographs

The combination of high spatial and spectral resolution in optical astronomy enables new observational approaches to many open problems in stellar and circumstellar astrophysics. However, constructing a high-resolution spectrograph for an interferometer is a costly and time-intensive undertaking. Our aim is to show that, by coupling existing high-resolution spectrographs to existing interferometers, one could observe in the domain of high spectral and spatial resolution, and avoid the construction of a new complex and expensive instrument. We investigate in this article the different challenges which arise from combining an interferometer with a high-resolution spectrograph. The requirements for the different sub-systems are determined, with special attention given to the problems of fringe tracking and dispersion. A concept study for the combination of the VLTI (Very Large Telescope Interferometer) with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other specific instrument pairings are discussed. We show that the proposed combination of an interferometer with a high-resolution spectrograph is indeed feasible with current technology, for a fraction of the cost of building a whole new spectrograph. The impact on the existing instruments and their ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio