Comparison of morphological and molecular genetic sex-typing on mediaeval human skeletal remains

Archaeological excavations conducted at an early mediaeval cemetery in Volders (Tyrol, Austria) produced 141 complete skeletal remains dated between the 5th/6th and 12th/13th centuries. These skeletons represent one of the largest historical series of human remains ever discovered in the East Alpine region. Little historical information is available for this region and time period. The good state of preservation of these bioarchaeological finds offered the opportunity of performing molecular genetic investigations. Adequate DNA extraction methods were tested in the attempt to obtain as high DNA yields as possible for further analyses. Molecular genetic sex-typing using a dedicated PCR multiplex (“Genderplex”) gave interpretable results in 88 remains, 78 of which had previously been sexed based on morphological features. We observed a discrepancy in sex determination between the two methods in 21 cases. An unbiased follow-up morphological examination of these finds showed congruence with the DNA results in all but five samples.     

Estimating fall risk with inertial sensors using gait stability measures that do not require step detection

Falls have major consequences both at societal (health-care and economy) and individual (physical and psychological) levels. Questionnaires to assess fall risk are commonly used in the clinic, but their predictive value is limited. Objective methods, suitable for clinical application, are hence needed to obtain a quantitative assessment of individual fall risk. Falls in older adults often occur during walking and trunk position is known to play a critical role in balance control. Therefore, analysis of trunk kinematics during gait could present a viable approach to the development of such methods. In this study, nonlinear measures such as harmonic ratio (HR), index of harmonicity (IH), multiscale entropy (MSE) and recurrence quantification analysis (RQA) of trunk accelerations were calculated. These measures are not dependent on step detection, a potentially critical source of error. The aim of the present study was to investigate the association between the aforementioned measures and fall history in a large sample of subjects (42 fallers and 89 non-fallers) aged 50 or older. Univariate associations with fall history were found for MSE and RQA parameters in the AP direction; the best classification results were obtained for MSE with scale factor τ = 2 and for maximum length of diagonals in RQA (72.5% and 71% correct classifications, respectively). MSE and RQA were found to be positively associated with fall history and could hence represent useful tools in the identification of subjects for fall prevention programs.     

Parameter Identification in Uncertain Scalar Conservation Laws Discretized with the Discontinuous Stochastic Galerkin Scheme

We study an identification problem which estimates the parameters of the underlying random distribution for uncertain scalar conservation laws. The hyperbolic equations are discretized with the so-called discontinuous stochastic Galerkin method, i.e., using a spatial discontinuous Galerkin scheme and a Multielement stochastic Galerkin ansatz in the random space. We assume an uncertain flux or uncertain initial conditions and that a data set of an observed solution is given. The uncertainty is assumed to be uniformly distributed on an unknown interval and we focus on identifying the correct endpoints of this interval. The first-order optimality conditions from the discontinuous stochastic Galerkin discretization are computed on the time-continuous level. Then, we solve the resulting semi-discrete forward and backward schemes with the Runge-Kutta method. To illustrate the feasibility of the approach, we apply the method to a stochastic advection and a stochastic equation of Burgers' type. The results show that the method is able to identify the distribution parameters of the random variable in the uncertain differential equation even if discontinuities are present.     

Comparing calculated and experimental activity and dose values obtained from image-based quantification of 90Y SPECT/CT Data

PurposeSelective internal radiation therapy (SIRT) is a treatment for various kinds of liver tumours by injecting ⁹⁰Y bearing microspheres into the liver vessels. To perform meaningful post-treatment dosimetry, quantitative imaging is performed.MethodsThis work uses a Monte-Carlo based reconstruction software with scatter and attenuation correction and collimator modelling that allows the quantification of ⁹⁰Y bremsstrahlung SPECT/CT data. A dataset comprising 17 patients and measurements on a Jaszczak phantom, a NEMA IEC Body phantom and an anthropomorphic liver phantom are analysed and activities and dose values are acquired. These measured values are compared with applied activities and pre-treatment calculations, allowing to assess the quality of the SPECT reconstruction. A detailed uncertainty budget is presented, including uncertainties of the dose calibrator, the count rate, non-included interactions and other factors.ResultsThe applied method is validated by finding measurements repeatable within the given uncertainty, and it is shown the influence of various parameters on the reconstruction process is negligible. Furthermore, activities and doses measured in the phantoms show good agreement with calculated values, if they are corrected for partial volume effects.ConclusionsThe strict observation of metrological requirements and the creation of an uncertainty budget increase the reliability and traceability of this novel approach to ⁹⁰Y dosimetry. It gives an example of successful voxel-based dosimetry based on quantitative ⁹⁰Y SPECT/CT image data.     

Triple‐echo steady‐state T2 relaxometry of the human brain at high to ultra‐high fields

Quantitative MRI techniques, such as T₂ relaxometry, have demonstrated the potential to detect changes in the tissue microstructure of the human brain with higher specificity to the underlying pathology than in conventional morphological imaging. At high to ultra‐high field strengths, quantitative MR‐based tissue characterization benefits from the higher signal‐to‐noise ratio traded for either improved resolution or reduced scan time, but is impaired by severe static (B₀) and transmit (B₁) field heterogeneities. The objective of this study was to derive a robust relaxometry technique for fast T₂ mapping of the human brain at high to ultra‐high fields, which is highly insensitive to B₀ and B₁ field variations. The proposed method relies on a recently presented three‐dimensional (3D) triple‐echo steady‐state (TESS) imaging approach that has proven to be suitable for fast intrinsically B₁‐insensitive T₂ relaxometry of rigid targets. In this work, 3D TESS imaging is adapted for rapid high‐ to ultra‐high‐field two‐dimensional (2D) acquisitions. The achieved short scan times of 2D TESS measurements reduce motion sensitivity and make TESS‐based T₂ quantification feasible in the brain. After validation in vitro and in vivo at 3 T, T₂ maps of the human brain were obtained at 7 and 9.4 T. Excellent agreement between TESS‐based T₂ measurements and reference single‐echo spin‐echo data was found in vitro and in vivo at 3 T, and T₂ relaxometry based on TESS imaging was proven to be feasible and reliable in the human brain at 7 and 9.4 T. Although prominent B₀ and B₁ field variations occur at ultra‐high fields, the T₂ maps obtained show no B₀‐ or B₁‐related degradations. In conclusion, as a result of the observed robustness, TESS T₂ may emerge as a valuable measure for the early diagnosis and progression monitoring of brain diseases in high‐resolution 2D acquisitions at high to ultra‐high fields. Copyright © 2014 John Wiley & Sons, Ltd.     

Clinical performance of the novel DiaSorin LIAISON® XL murex: HBsAg Quant,HCV-Ab,HIV-Ab/Ag assays

BackgroundThe fully automated and closed LIAISON^®XL platform was developed for reliable detection of infection markers like hepatitis B virus (HBV) surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab) or human immunodeficiency virus (HIV)-Ag/Ab. To date, less is known about the diagnostic performance of this system in direct comparison to the common Abbott ARCHITECT^® platform.ObjectivesWe compared the diagnostic performance and usability of the DiaSorin LIAISON^®XL with the commonly used Abbott ARCHITECT^® system.Study designThe qualitative performance of the above mentioned assays was compared in about 500 sera. Quantitative tests were performed for HBsAg-positive samples from patients under therapy (n = 289) and in vitro expressed mutants (n = 37). For HCV-Ab, a total number of 155 selected samples from patients chronically infected with different HCV genotypes were tested.ResultsThe concordance between both systems was 99.4% for HBsAg, 98.81% for HCV-Ab, and 99.6% for HIV-Ab/Ag. The quantitative LIAISON^®XL murex HBsAg assay detected all mutants in comparable amounts to the HBsAg wild type and yielded highly reliable HBsAg kinetics in patients treated with antiviral drugs. Dilution experiments using the 2nd International Standard for HBsAg (WHO) showed a high accuracy of this test. HCV-Ab from patients infected with genotypes 1–3 were equally detected in both systems. Interestingly, S/CO levels of HCV-Ab from patients infected with genotype 3 seem to be relatively low using both systems.ConclusionsThe LIAISON^®XL platform proved to be an excellent system for diagnostics of HBV, HCV, and HIV with equal performance compared to the ARCHITECT^® system.     

A practical guide for the study of human and murine sebaceous glands in situ

The skin of most mammals is characterised by the presence of sebaceous glands (SGs), whose predominant constituent cell population is sebocytes, that is, lipid‐producing epithelial cells, which develop from the hair follicle. Besides holocrine sebum production (which contributes 90% of skin surface lipids), multiple additional SG functions have emerged. These range from antimicrobial peptide production and immunomodulation, via lipid and hormone synthesis/metabolism, to the provision of an epithelial progenitor cell reservoir. Therefore, in addition to its involvement in common skin diseases (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin health and disease, has raised interest in this integral component of the pilosebaceous unit. This practical guide provides an introduction to SG biology and to relevant SG histochemical and immunohistochemical techniques, with emphasis placed on in situ evaluation methods that can be easily employed. We propose a range of simple, established markers, which are particularly instructive when addressing specific SG research questions in the two most commonly investigated species in SG research, humans and mice. To facilitate the development of reproducible analysis techniques for the in situ evaluation of SGs, this methods review concludes by suggesting quantitative (immuno‐)histomorphometric methods for standardised SG evaluation.     

VaxArray assessment of influenza split vaccine potency and stability

Vaccine manufacturers require more rapid and accurate tools to characterize the potency and stability of their products. Currently, the gold standard for influenza vaccine potency is the single radial immunodiffusion (SRD) assay, which has inherent disadvantages. The primary objective of this study was to investigate the ability of the VaxArray Influenza (VXI) seasonal hemagglutinin (sHA) potency assay to accurately quantify potency and stability in finished vaccines as well as to quantify hemagglutinin protein (HA) within crude in-process samples. Monobulk intermediates and mono- and multivalent vaccines were tested using VXI. Quantification of HA in crude samples was evaluated by spiking known concentrations of HA into allantoic fluid. VXI generated SRD equivalent potency measurements with high accuracy (within ±10%) and precision (CV 10 ± 4%) for antigen components of monobulk intermediates and multivalent split vaccines. For these vaccines and vaccine intermediates, the VXI linear dynamic range was ∼0.01–0.6 μg/mL, which is 12× greater than the linear range of SRD. The measured sample limit of detection (LOD) for VXI varied from 0.005 to 0.01 μg/mL for the different subtypes, which in general is ≥600× lower than the LOD for SRD. VXI was able to quantify HA in crude samples where HA only accounts for 0.02% of the total protein content. Stability indication was investigated by tracking measured potency as a function of time at elevated temperature by both SRD and VXI. After 20 h at 56 °C, the ratio of VXI to SRD measured potency in a quadrivalent vaccine was 76%, 125%, 60%, and 98% for H1/California, H3/Switzerland, B/Phuket and B/Brisbane, respectively. Based on the study results, it is concluded that VXI is a rapid, multiplexed immunoassay that can be used to accurately determine flu vaccine potency and stability in finished product and in crude samples from upstream processes.