[Differential osteoporosis diagnosis in the woman]

Bone mineral density of a woman in the second half of her life depends on the amount of bone made during growth and its subsequent rate of loss. Although the rate of bone loss did receive more attention in the study of pathogenesis of osteoporosis, it is becoming increasingly clear that insufficient accumulation of skeletal mass by young adulthood predisposes a person to low bone mass and subsequently to fractures later in life as age related and menopause-related bone loss ensue. In this article we 1) explain the role of inadequate peak bone mass as a major risk factor for osteoporosis and 2) give an overview of factors leading to osteoporosis by decreasing bone mass. Special emphasis has been put on iatrogenic osteoporosis which is frequently neglected because of the fact that the responsible agents often are not known as to be deleterious to the skeleton: among others, glucocorticoids, thyroid hormones and antiepileptics adversely affect bone.

Tropical cyclone-related socio-economic losses in the western North Pacific region

The western North Pacific (WNP) is the area of the world most frequently affected by tropical cyclones (TCs). However, little is known about the socio-economic impacts of TCs in this region, probably because of the limited relevant loss data. Here, loss data from Munich RE's NatCatSERVICE database is used, a high-quality and widely consulted database of natural disasters. In the country-level loss normalisation technique we apply, the original loss data are normalised to present-day exposure levels by using the respective country's nominal gross domestic product at purchasing power parity as a proxy for wealth. The main focus of our study is on the question of whether the decadal-scale TC variability observed in the Northwest Pacific region in recent decades can be shown to manifest itself economically in an associated variability in losses. It is shown that since 1980 the frequency of TC-related loss events in the WNP exhibited, apart from seasonal and interannual variations, interdecadal variability with a period of about 22 yr – driven primarily by corresponding variations of Northwest Pacific TCs. Compared to the long-term mean, the number of loss events was found to be higher (lower) by 14% (9%) in the positive (negative) phase of the decadal-scale WNP TC frequency variability. This was identified for the period 1980–2008 by applying a wavelet analysis technique. It was also possible to demonstrate the same low-frequency variability in normalised direct economic losses from TCs in the WNP region. The identification of possible physical mechanisms responsible for the observed decadal-scale Northwest Pacific TC variability will be the subject of future research, even if suggestions have already been made in earlier studies.

Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency

In the present study, we wanted to (1) evaluate whether high-sensitive troponin T levels correlate with the grade of renal insufficiency and (2) test the accuracy of high-sensitive troponin T determination in patients with renal insufficiency for diagnosis of acute myocardial infarction (AMI). In this cross-sectional analysis, all patients who received serial measurements of high-sensitive troponin T from August 1, 2010, to October 31, 2012, at the Department of Emergency Medicine were included. We analyzed data on baseline characteristics, reason for referral, medication, cardiovascular risk factors, and outcome in terms of presence of AMI along with laboratory data (high-sensitive troponin T, creatinine). A total of 1,514 patients (67% male, aged 65 ± 16 years) were included, of which 382 patients (25%) had moderate to severe renal insufficiency and significantly higher levels of high-sensitive troponin T on admission (0.028 vs 0.009, p <0.0001). In patients without AMI, high-sensitive troponin T correlated inversely with the estimated glomerular filtration rate (R = -0.12, p <0.0001). Overall, sensitivity of an elevated high-sensitive troponin for diagnosis of AMI was 0.64 (0.56 to 0.71) and the specificity was 0.48 (0.45 to 0.51). The area under the curve of the receiver operating characteristic for all patients was 0.613 (standard error [SE] 0.023), whereas it was 0.741 (SE 0.029) for patients with a Modification of Diet in Renal Disease estimated glomerular filtration rate >60 ml/min presenting with acute chest pain or dyspnea and 0.535 (SE 0.056) for patients with moderate to severe renal insufficiency presenting with acute chest pain or dyspnea. In conclusion, the diagnostic accuracy for presence of AMI of a baseline measurement of high-sensitive troponin in patients with renal insufficiency was poor and resembles tossing a coin.

Sex identification and PIT-tagging: tools and prospects for studying intersexual differences in freshwater fishes

This study evaluated a technique to allow the long-term monitoring of individual fishes of known sex in the wild using sex confirmation in close proximity to the reproductive period combined with individual tagging. Hundreds of partially migratory roach Rutilus rutilus were tagged with passive integrated transponders (PIT) following sex determination in spring and various performance measures were compared with fish tagged outside the reproductive period in autumn. Short-term survival was > 95% for R. rutilus sexed and tagged under natural field conditions. Total length (LT) did not affect the probability of survival within the size range tagged (119–280mm), nor were there differences in timing of migration the following season between individuals sexed and tagged in spring and individuals tagged in autumn (i.e. outside the reproductive period). Also, a similar per cent of R. rutilus sexed and tagged in spring and tagged in autumn migrated the following season (34·5 and 34·7%). Moreover, long-term recapture data revealed no significant differences in body condition between R. rutilus individuals sexed and tagged in spring, individuals tagged in autumn and unmanipulated individuals. The observed sex ratio of recaptured fish did not differ from the expected values of equal recapture rates between males and females. Hence, there is no observable evidence for an adverse effect of tagging close to the reproductive period and therefore this method is suitable for studying intersexual differences and other phenotypic traits temporarily expressed during reproduction at the individual level in fishes.

Cyclophosphamide: As bad as its reputation? Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases

OBJECTIVES Despite new treatment modalities, cyclophosphamide (CYC) remains a cornerstone in the treatment of organ or life-threatening vasculitides and connective tissue disorders. We aimed at analysing the short- and long-term side-effects of CYC treatment in patients with systemic autoimmune diseases. METHODS Chart review and phone interviews regarding side effects of CYC in patients with systemic autoimmune diseases treated between 1984 and 2011 in a single university centre. Adverse events were stratified according to the "Common Terminology Criteria for Adverse Events" version 4. RESULTS A total of 168 patients were included. Cumulative CYC dose was 7.45 g (range 0.5-205 g). Gastro-intestinal side effects were seen in 68 events, hair loss occurred in 38 events. A total of 58 infections were diagnosed in 44/168 patients (26.2%) with 9/44 suffering multiple infections. Severity grading of infections was low in 37/58 cases (63.8%). One CYC-related infection-induced death (0.6%) was registered. Amenorrhoea occurred in 7/92 females (7.6%) with 5/7 remaining irreversible. In females with reversible amenorrhoea, prophylaxis with nafarelin had been administered. Malignancy was registered in 19 patients after 4.7 years (median, range 0.25-22.25) presenting as 4 premalignancies and 18 malignancies, 3 patients suffered 2 premalignancies/malignancies each. Patients with malignancies were older with a higher cumulative CYC dose. Death was registered in 28 patients (16.6%) with 2/28 probably related to CYC. CONCLUSIONS Considering the organ or life-threatening conditions which indicate the use of CYC, severe drug-induced health problems were rare. Our data confirm the necessity to follow-up patients long-term for timely diagnosis of malignancies. CYC side-effects do not per se justify prescription of newer drugs or biologic agents in the treatment of autoimmune diseases.

CODE’s new solar radiation pressure model for GNSS orbit determination

The Empirical CODE Orbit Model (ECOM) of the Center for Orbit Determination in Europe (CODE), which was developed in the early 1990s, is widely used in the International GNSS Service (IGS) community. For a rather long time, spurious spectral lines are known to exist in geophysical parameters, in particular in the Earth Rotation Parameters (ERPs) and in the estimated geocenter coordinates, which could recently be attributed to the ECOM. These effects grew creepingly with the increasing influence of the GLONASS system in recent years in the CODE analysis, which is based on a rigorous combination of GPS and GLONASS since May 2003. In a first step we show that the problems associated with the ECOM are to the largest extent caused by the GLONASS, which was reaching full deployment by the end of 2011. GPS-only, GLONASS-only, and combined GPS/GLONASS solutions using the observations in the years 2009–2011 of a global network of 92 combined GPS/GLONASS receivers were analyzed for this purpose. In a second step we review direct solar radiation pressure (SRP) models for GNSS satellites. We demonstrate that only even-order short-period harmonic perturbations acting along the direction Sun-satellite occur for GPS and GLONASS satellites, and only odd-order perturbations acting along the direction perpendicular to both, the vector Sun-satellite and the spacecraft’s solar panel axis. Based on this insight we assess in the third step the performance of four candidate orbit models for the future ECOM. The geocenter coordinates, the ERP differences w. r. t. the IERS 08 C04 series of ERPs, the misclosures for the midnight epochs of the daily orbital arcs, and scale parameters of Helmert transformations for station coordinates serve as quality criteria. The old and updated ECOM are validated in addition with satellite laser ranging (SLR) observations and by comparing the orbits to those of the IGS and other analysis centers. Based on all tests, we present a new extended ECOM which substantially reduces the spurious signals in the geocenter coordinate z (by about a factor of 2–6), reduces the orbit misclosures at the day boundaries by about 10 %, slightly improves the consistency of the estimated ERPs with those of the IERS 08 C04 Earth rotation series, and substantially reduces the systematics in the SLR validation of the GNSS orbits.

8p23 beta-defensin copy number determination by single-locus pseudogene-based paralog ratio tests risk bias due to low-frequency sequence variations.

BACKGROUND The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. RESULTS We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. CONCLUSION MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.

The mobility of Nb in rutile-saturated NaCl- and NaF-bearing aqueous fluids from 1-6.5 GPa and 300-800 °C

Rutile (TiO2) is an important host phase for high field strength elements (HFSE) such as Nb in metamorphic and subduction zone environments. The observed depletion of Nb in arc rocks is often explained by the hypothesis that rutile sequesters HFSE in the subducted slab and overlying sediment, and is chemically inert with respect to aqueous fluids evolved during prograde metamorphism in the forearc to subarc environment. However, field observations of exhumed terranes, and experimental studies, indicate that HFSE may be soluble in complex aqueous fluids at high pressure (i.e., >0.5 GPa) and moderate to high temperature (i.e., >300 degrees C). In this study, we investigated experimentally the mobility of Nb in NaCl- and NaF-bearing aqueous fluids in equilibrium with Nb-bearing rutile at pressure-temperature conditions applicable to fluid evolution in arc environments. Niobium concentrations in aqueous fluid at rutile saturation were measured directly by using a hydrothermal diamond-anvil cell (HDAC) and synchrotron X-ray fluorescence (SXRF) at 2.1 to 6.5 GPa and 300-500 degrees C, and indirectly by performing mass loss experiments in a piston-cylinder (PC) apparatus at similar to 1 GPa and 700-800 degrees C. The concentration of Nb in a 10 wt% NaCl aqueous fluid increases from 6 to 11 mu g/g as temperature increases from 300 to 500 degrees C, over a pressure range from 2.1 to 2.8 GPa, consistent with a positive temperature dependence. The concentration of Nb in a 20 wt% NaCl aqueous fluid varies from 55 to 150 mu g/g at 300 to 500 degrees C, over a pressure range from 1.8 to 6.4 GPa; however, there is no discernible temperature or pressure dependence. The Nb concentration in a 4 wt% NaF-bearing aqueous fluid increases from 180 to 910 mu g/g as temperature increases from 300 to 500 degrees C over the pressure range 2.1 to 6.5 GPa. The data for the F-bearing fluid indicate that the Nb content of the fluid exhibits a dependence on temperature between 300 and 500 degrees C at >= 2 GPa, but there is no observed dependence on pressure. Together, the data demonstrate that the hydrothermal mobility of Nb is strongly controlled by the composition of the fluid, consistent with published data for Ti. At all experimental conditions, however, the concentration of Nb in the fluid is always lower than coexisting rutile, consistent with a role for rutile in moderating the Nb budget of arc rocks.

Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor.

Due to the lack of regenerative capacity of the mammalian auditory epithelium, sensory hair cell loss results in permanent hearing deficit. Nevertheless, a population of tissue resident stem/progenitor cells has been recently described. Identification of methods to trigger their activity could lead to exploitation of their potential therapeutically. Here we validate the use of transgenic mice reporting cell cycle progression (FUCCI), and stemness (Lgr5-GFP), as a valuable tool to identify regulators of cell cycle re-entry of supporting cells within the auditory epithelium. The small molecule compound CHIR99021 was used to inhibit GSK3 activity. This led to a significant increase in the fraction of proliferating sphere-forming cells, labeled by the FUCCI markers and in the percentage of Lgr5-GFP + cells, as well as a selective increase in the fraction of S-G2-M cells in the Lgr5 + population. Using whole mount cultures of the organ of Corti we detected a statistically significant increment in the fraction of proliferating Sox2 supporting cells after CHIR99021 treatment, but only rarely appearance of novel MyoVIIa+/Edu + hair cells. In conclusion, these tools provide a robust mean to identify novel regulators of auditory organ regeneration and to clarify the contribution of stem cell activity.

Structural brain correlates of defective gesture performance in schizophrenia

INTRODUCTION The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. METHODS We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cut-off scores were used to separate patients with deficits, patients without deficits and controls. Group differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS Patients performed poorer than controls in each gesture category (p < .001). Patients with deficits in producing meaningful gestures on command had reduced GM predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe (IPL) and superior temporal gyrus. CONCLUSIONS Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations. However, few associations between behavioral impairment and structural brain alterations appear specific to schizophrenia.

In-situ Iron isotope measurements and mineral compositions from ODP Hole 206-1256D and IODP Hole 335-U1256D

In-situ Fe isotope measurements have been carried out to estimate the impact of the hydrothermal metamorphic overprint on the Fe isotopic composition of Fe-Ti-oxides and Fe-sulfides of the different lithologies of the drilled rocks from IODP Hole 1256D (eastern equatorial Pacific; 15 Ma crust formed at the East Pacific Rise). Most igneous rocks normally have a very restricted range in their 56Fe/54Fe ratio. In contrast, Fe isotope compositions of hot fluids (> 300 °C) from mid-ocean-ridge spreading centers define a narrow range that is shifted to lower delta 56Fe values by 0.2 per mil - 0.5 per mil as compared to igneous rocks. Therefore, it is expected that mineral phases that contain large amounts of Fe are especially affected by the interaction with a fluid that fractionates Fe isotopes during exsolution/precipitation of those minerals. We have used a femtosecond UV-Laser ablation system to determine mineral 56Fe/54Fe ratios of selected samples with a precision of < 0.1 per mil (2 sigma level) at micrometer-scale. We have found significant variations of the delta 56Fe (IRMM-014) values in the minerals between different samples as well as within samples and mineral grains. The overall observed scale of delta 56Fe (magnetite) in 1256D rocks ranges from - 0.12 to + 0.64 per mil, and of delta 56Fe (ilmenite) from - 0.77 to + 0.01 per mil. Pyrite in the lowermost sheeted dike section is clearly distinguishable from the other investigated lithological units, having positive delta 56Fe values between + 0.29 and + 0.56 per mil, whereas pyrite in the other samples has generally negative delta 56Fe values from - 1.10 to - 0.59 permil. One key observation is that the temperature dependent inter-mineral fractionations of Fe isotopes between magnetite and ilmenite are systematically shifted towards higher values when compared to theoretically expected values, while synthesized, well equilibrated magnetite-ilmenite pairs are compatible with the theoretical predictions. Theoretical considerations including beta-factors of different aqueous Fe-chlorides and Rayleigh-type fractionations in the presence of a hydrous, chlorine-bearing fluid can explain this observation. The disagreement between observed and theoretical equilibrium fractionation, the fact that magnetite, in contrast to ilmenite shows a slight downhole trend in the delta 56Fe values, and the observation of small scale heterogeneities within single mineral grains imply that a general re-equilibration of the magnetite-ilmenite pairs is overprinted by kinetic fractionation effects, caused by the interaction of magnetite/ilmenite with hydrothermal fluids penetrating the upper oceanic crust during cooling, or incomplete re-equilibration at low temperatures. Furthermore, the observation of significant small-scale variations in the 56Fe/54Fe ratios of single minerals in this study highlights the importance of high spatial-resolution-analyses of stable isotope ratios for further investigations.

Some hydrophysical and hydrochemical parameters of the upper part of the hydrogen sulfide zone in the Black Sea, September 11-22, 1994

Features of spatial variability of hydrogen sulfide in the northeastern part of the Black Sea are estimated. Some technical aspects of H2S concentration determination in the anoxic zone are discussed: in its upper part at H2S concentration <30 µmol/l, the photometric method is recommended, while for deeper layers the iodometric method should be used. With linearity of vertical distribution of hydrogen sulfide and ammonium taken into account their vertical gradients are estimated as 0.49+/-0.04 µmol/m and 0.19+/-0.06 µmol/m respectively. It is shown that the upper boundary of the H2S layer corresponds to the isopycnal surface with Sigma_t = 16.19+/-0.05 arbitrary units. Special attention is paid to relationship of hydrogen sulfide distribution with hydrophysical features in the region under study, in particular in the coastal zone. It is shown that hydrodynamic conditions control spatial distribution of hydrogen sulfide. On the basis of isopycnal treatment of the H2S field existence of a coastal convergence zone is proved, and peculiarities are recognized of vertical circulation in the main Black Sea gyre and coastal anticyclonic eddies; here hydrogen sulfide serves as a tracer of hydrophysical mixing processes.

Plant frequency and cover abundance at three sites on Disko Island in 1967/1970 and 2009

We report on a revisit in 2009 to sites where vegetation was recorded in 1967 and 1970 on Disko Island, West Greenland. Re-sampling of the same clones of the grass Phleum alpinum after 39 years showed complete stability in biometrics but dramatic earlier onset of various phenological stages that were not related to changes in population density. In a fell-field community, there was a net species loss, but in a herb-slope community, species losses balanced those that were gained. The type of species establishing and increasing in frequency and/or cover abundance at the fell-field site, particularly prostrate dwarf shrubs, indicates a possible start of a shift towards a heath, rather than a fell-field community. At the herb-slope site, those species that established or increased markedly in frequency and/or cover abundance indicate a change to drier conditions. This is confirmed both by the decrease in abundance of Alchemilla glomerulans and Epilobium hornemanii, and the drying of a nearby pond. The causes of these changes are unknown, although mean annual temperature has risen since 1984.

Spatial and seasonal distribution of Thaumarchaeota in the water column and sediment of the southern North Sea

We have examined the spatial and seasonal distribution of Thaumarchaeota in the water column and sediment of the southern North Sea using the specific intact polar lipid (IPL) hexose, phosphohexose (HPH) crenarchaeol, as well as thaumarchaeotal 16S rRNA gene abundances and expression. In the water column, a higher abundance of Thaumarchaeota was observed in the winter season than in the summer, which is in agreement with previous studies, but this was not the case in the sediment where Thaumarchaeota were most abundant in spring and summer. This observation corresponds well with the idea that ammonia availability is a key factor in thaumarchaeotal niche determination. In the surface waters of the southern North Sea, we observed a spatial variability in HPH crenarchaeol, thaumarchaeotal 16S rRNA gene abundance and transcriptional activity that corresponded well with the different water masses present. In bottom waters, a clear differentiation based on water masses was not observed; instead, we suggest that observed differences in thaumarchaeotal abundance with depth may be related to resuspension from the sediment. This could be due to suspension of benthic Thaumarchaeota to the water column or due to delivery of e.g. resuspended sediment or ammonium to the water column, which could be utilized by pelagic Thaumarchaeota. This study has shown that the seasonality of Thaumarchaeota in water and sediment is different and highlights the importance of water masses, currents and sedimentary processes in determining the spatial abundance of Thaumarchaeota in the southern North Sea.

Experimental results for Myopic Loss Aversion

This data is experimental results of "Myopic Loss Aversion: An Experimental Analysis for the Flexibility of Investment and the Frequency of Information Feedback Using Two Period Binomial Stock Model".