Bone age estimation with the Greulich-Pyle atlas using 3T MR images of hand and wrist.

The age estimation of the hand bones by means of X-ray examination is a pillar of the forensic age estimation. Since the associated radiation exposure is controversial, the search for ionizing radiation-free alternatives such as MRI is part of forensic research. The aim of the current study was to use the Greulich-Pyle (GP) atlas on MR images of the hand and wrist to provide reference values for assessing the age of the hand bones. 3T hand MR images of 238 male participants between the ages of 13 and 21 were acquired using 3D gradient echo sequences (VIBE, DESS). Two readers rated the images using the X-ray-based GP atlas method. A descriptive analysis and a transitional analysis were used for the statistical processing of the data. The agreement between and within the raters was assessed. In addition, a comparison was made with the chronological age and with X-ray studies. The descriptive analysis and the transition analysis showed similar results. Both evaluations showed good agreement with X-ray studies. The comparison with the chronological age showed a difference of 0.37 and 0.54 years for the two readers. The age estimate based on the cross-validated transition analysis showed a mean error of -0.28 years. Inter- and intra-rater agreement were good. In summary, it can be concluded that age estimation of hand bones with MR images is routinely applicable with the GP atlas as an alternative without ionizing radiation. However, in order to reduce the estimation error, a multi-factorial assessment based on examinations of several body regions is still recommended

Temperature dependence of viscosity, relaxation times (T1, T2) and simulated contrast for potential perfusates in post-mortem MR angiography (PMMRA).

Developments in post-mortem imaging increasingly focus on addressing recognised diagnostic weaknesses, especially with regard to suspected natural deaths. Post-mortem MR angiography (PMMRA) may offer additional diagnostic information to help address such weaknesses, specifically in the context of sudden cardiac death. Complete filling of the coronary arteries and acceptable contrast with surrounding tissue are essential for a successful approach to PMMRA. In this work, the suitability of different liquids for inclusion in a targeted PMMRA protocol was evaluated. Factors influencing cooling of paraffinum liquidum + Angiofil® (6 %) in cadavers during routine multiphase post-mortem CT angiography were investigated. The temperature dependence of dynamic viscosity (8-20 °C), longitudinal (T1) and transverse (T2) relaxation (1-23 °C) of the proposed liquids was quadratically modelled. The relaxation behaviour of these liquids and MR scan parameters were further investigated by simulation of a radiofrequency (RF)-spoiled gradient echo (GRE) sequence to estimate potentially achievable contrast between liquids and post-mortem tissue at different temperatures across a forensically relevant temperature range. Analysis of the established models and simulations indicated that based on dynamic viscosity (27-33 mPa · s), short T1 relaxation times (155-207 ms) and a minimal temperature dependence over the investigated range of these parameters, paraffin oil and a solution of paraffin oil + Angiofil® (6 %) would be most suitable for post-mortem reperfusion and examination in MRI

Dynamic microRNA activity identifies therapeutic targets in trastuzumab‐resistant HER2+ breast cancer

MicroRNAs (miRNAs) are implicated in numerous physiologic and pathologic processes, such as the development of resistance to chemotherapy. Determining the role of miRNAs in these processes is often accomplished through measuring miRNA abundance by polymerase chain reaction, sequencing, or microarrays. We have developed a system for the large‐scale monitoring of dynamic miRNA activity and have applied this system to identify the contribution miRNA activity to the development of trastuzumab resistance in a cell model of HER2+ breast cancer. MiRNA activity measurements identified significantly different activity levels between BT474 cells (HER2+ breast cancer) and BT474R cells (HER2+ breast cancer cells selected for resistance to trastuzumab). We created a library of 32 miRNA reporter constructs, which were delivered by lentiviral transduction into cells, and miRNA activity was quantified by bioluminescence imaging. Upon treatment with the bioimmune therapy, trastuzumab, the activity of 11 miRNAs were significantly altered in parental BT474 cells, and 20 miRNAs had significantly altered activity in the therapy‐resistant BT474R cell line. A combination of statistical, network and classification analysis was applied to the dynamic data, which identified miR‐21 as a controlling factor in trastuzumab response. Our data suggested downregulation of miR‐21 activity was associated with resistance, which was confirmed in an additional HER2+ breast cancer cell line, SKBR3. Collectively, the dynamic miRNA activity measurements and analysis provided a system to identify new potential therapeutic targets in treatment‐resistant cancers.MicroRNAs (miRNAs) are often dysrgulated in cancer and can give rise to drug resistance. Identifying the mechanisms for resistance may lead to new This work used an array of miRNA activity reporters to identify miR‐21 as a mediator of trastuzumab resistance in breast cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146392/1/bit26791.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146392/2/bit26791_am.pd

Surface embedding, topology and dualization for spin networks

Spin networks are graphs derived from 3nj symbols of angular momentum. The surface embedding, the topology and dualization of these networks are considered. Embeddings into compact surfaces include the orientable sphere S^2 and the torus T, and the not orientable projective space P^2 and Klein's bottle K. Two families of 3nj graphs admit embeddings of minimal genus into S^2 and P^2. Their dual 2-skeletons are shown to be triangulations of these surfaces.Comment: LaTeX 17 pages, 6 eps figures (late submission to arxiv.org

Changes of palaeoenvironmental conditions recorded in Late Devonian reef systems from the Canning Basin, Western Australia: A biomarker and stable isotope approach

Although the Late Devonian extinctions were amongst the largest mass extinction events in the Phanerozoic, the causes, nature and timing of these events remain poorly restrained. In addition to the most pronounced biodiversity loss at the Frasnian–Famennian (F–F) boundary and the end Famennian, there were also less extensively studied extinction pulses in the Middle to Late Givetian and the Frasnian. Here we used a combination of palynological, elemental, molecular and stable isotope analyses to investigate a sedimentary record of reef-systems from this time period in the Canning Basin, Western Australia. The acquired data generally showed distinct variations between sediments from (i) the time around the Givetian–Frasnian (G–F) boundary and (ii) later in the Frasnian and indicated a distinct interval of biotic stress, particularly for reef-builders, in the older sediments. Alterations of pristane/phytane ratios, gammacerane indices, Chlorobi biomarkers, δDkerogen and chroman ratios describe the change from a restricted marine palaeoenvironment with an anoxic/euxinic hypolimnion towards a presumably open marine setting with a vertically mixed oxic to suboxic water column. Simultaneous excursions in δ13C profiles of carbonates, organic matter (OM) and hydrocarbons in the older sediments reflect the stratification-induced enhancement of OM-recycling by sulfate reducing bacteria. Alterations in sterane distributions and elevated abundances of methyltrimethyltridecylchromans (MTTCs) and perylene indicate an increased terrigenous nutrient input via riverine influx, which would have promoted stratification, phytoplankton blooms and the development of lower water column anoxia.The detected palaeoenvironmental conditions around the G–F boundary may reflect a local or global extinction event. Our data furthermore suggest a contribution of the higher plant-expansion and photic zone euxinia to the Late Devonian extinctions, consistent with previous hypotheses. Furthermore, this work might contribute to the understanding of variations in Devonian reef margin and platform-top architecture, relevant for petroleum exploration and development in the global Devonian hydrocarbon resources

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

We can guide search by a set of colours, but are reluctant to do it.

For some real-world color searches, the target colours are not precisely known, and any item within a range of color values should be attended. This, a target representation that captures multiple similar colours would be advantageous. If such multicolour search is possible, then search for two targets (e..g Stroud, Menneer, Cave and Donnelly, 2012) might be guided by a target representation that included the target colours as well as the continuum of colours that fall between the targets within a contiguous region of color space. Results from Stroud et al (2012) suggest otherwise, however. The current set of experiments show that guidance for a set of colours that are from a single region of color space can be effective if targets are depicted as specific discrete colours. Specifically, Experiments 1-3 demonstrate that a search can be guided by four and even eight colours given the appropriate conditions. However, Experiment 5 gives evidence that guidance is sometimes sensitive to how informative the target preview is to search. Experiments 6 and 7 show that a stimulus showing a continuous range of target colours is not translated into a search target representation. Thus, search can be guided by multiple discrete colours that are from a single region in color space, but this approach was not adopted in a search for two targets with intervening distractor colours

A common polymorphism of the human cardiac sodium channel alpha subunit (SCN5A) gene is associated with sudden cardiac death in chronic ischemic heart disease

Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio =1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. © 2015 Marcsa 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

Microbial life in the nascent Chicxulub crater

The Chicxulub crater was formed by an asteroid impact at ca. 66 Ma. The impact is considered to have contributed to the end-Cretaceous mass extinction and reduced productivity in the world's oceans due to a transient cessation of photosynthesis. Here, biomarker profiles extracted from crater core material reveal exceptional insights into the post-impact upheaval and rapid recovery of microbial life. In the immediate hours to days after the impact, ocean resurge flooded the crater and a subsequent tsunami delivered debris from the surrounding carbonate ramp.  Deposited material, including biomarkers diagnostic for land plants, cyanobacteria, and photosynthetic sulfur bacteria, appears to have been mobilized by wave energy from coastal microbial mats. As that energy subsided, days to months later, blooms of unicellular cyanobacteria were fueled by terrigenous nutrients. Approximately 200 k.y. later, the nutrient supply waned and the basin returned to oligotrophic conditions, as evident from N2-fixing cyanobacteria biomarkers. At 1 m.y. after impact, the abundance of photosynthetic sulfur bacteria supported the development of water-column photic zone euxinia within the crater

Life and death in the Chicxulub impact crater: A record of the Paleocene-Eocene Thermal Maximum

Thermal stress on the biosphere during the extreme warmth of the Paleocene-Eocene Thermal Maximum (PETM) was most severe at low latitudes, with sea surface temperatures at some localities exceeding the 35 C at which marine organisms experience heat stress. Relatively few equivalent terrestrial sections have been identified, and the response of land plants to this extreme heat is still poorly understood. Here, we present a new record of the PETM from the peak ring of the Chicxulub impact crater that has been identified based on nannofossil biostratigraphy, an acme of the dinoflagellate genus Apectodinium, and a negative carbon isotope excursion. Geochemical and microfossil proxies show that the PETM is marked by elevated TEXH 86-based sea surface temperatures (SSTs) averaging 37:8 C, an in- crease in terrestrial input and surface productivity, salinity stratification, and bottom water anoxia, with biomarkers for green and purple sulfur bacteria indicative of photic zone euxinia in the early part of the event. Pollen and plants spores in this core provide the first PETM floral assemblage described from Mexico, Central America, and the northern Caribbean. The source area was a diverse coastal shrubby tropical forest with a remarkably high abundance of fungal spores, indicating humid conditions. Thus, while seafloor anoxia devastated the benthic marine biota and dinoflagellate assemblages were heat-stressed, the terrestrial plant ecosystem thrived