Thermoluminescence of zircon: a kinetic model

The mineral zircon, ZrSiO4, belongs to a class of promising materials for geochronometry by means of thermoluminescence (TL) dating. The development of a reliable and reproducible method for TL dating with zircon requires detailed knowledge of the processes taking place during exposure to ionizing radiation, long-term storage, annealing at moderate temperatures and heating at a constant rate (TL measurements). To understand these processes one needs a kinetic model of TL. This paper is devoted to the construction of such amodel. The goal is to study the qualitative behaviour of the system and to determine the parameters and processes controlling TL phenomena of zircon. The model considers the following processes: (i) Filling of electron and hole traps at the excitation stage as a function of the dose rate and the dose for both (low dose rate) natural and (high dose rate) laboratory irradiation. (ii) Time dependence of TL fading in samples irradiated under laboratory conditions. (iii) Short time annealing at a given temperature. (iv) Heating of the irradiated sample to simulate TL experiments both after laboratory and natural irradiation. The input parameters of the model, such as the types and concentrations of the TL centres and the energy distributions of the hole and electron traps, were obtained by analysing the experimental data on fading of the TL-emission spectra of samples from different geological locations. Electron paramagnetic resonance (EPR) data were used to establish the nature of the TL centres. Glow curves and 3D TL emission spectra are simulated and compared with the experimental data on time-dependent TL fading. The saturation and annealing behaviour of filled trap concentrations has been considered in the framework of the proposed kinetic model and comparedwith the EPR data associated with the rare-earth ions Tb3+ and Dy3+, which play a crucial role as hole traps and recombination centres. Inaddition, the behaviour of some of the SiOmn− centres has been compared with simulation results.

DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus

Background: DNA methylation is of pivotal importance during development. Previous genome-wide studies identified numerous differentially methylated regions upon differentiation of stem cells, many of them associated with transcriptional start sites. Results: We present the first genome-wide, single-base-resolution view into DNA methylation dynamics during differentiation of a mammalian epithelial stem cell: the mouse small intestinal Lgr5+ stem cell. Very little change was observed at transcriptional start sites and our data suggest that differentiation-related genes are already primed for expression in the stem cell. Genome-wide, only 50 differentially methylated regions were identified. Almost all of these loci represent enhancers driving gene expression in the differentiated part of the small intestine. Finally, we show that binding of the transcription factor Tcf4 correlates with hypo-methylation and demonstrate that Tcf4 is one of the factors contributing to formation of differentially methylated regions. Conclusions: Our results reveal limited DNA methylation dynamics during small intestine stem cell differentiation and an impact of transcription factor binding on shaping the DNA methylation landscape during differentiation of stem cells in vivo

Imaging strategies for detection of urgent conditions in patients with acute abdominal pain: diagnostic accuracy study

Objective To identify an optimal imaging strategy for the accurate detection of urgent conditions in patients with acute abdominal pain

Assessment of Bone Lesions with F-18-FDG PET Compared with Tc-99m Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by F-18-FDG PET instead of Tc-99m bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by (18)FFDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and F-18-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either F-18-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 10(2) evaluated patients (39% by ceCT, 26% by BS, and 87% by F-18-FDG PET). Additional bone lesions on F-18-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with F-18-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional F-18-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, F-18-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for F-18-FDG PET. On the basis of these data, F-18-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC

autoTICI: Automatic Brain Tissue Reperfusion Scoring on 2D DSA Images of Acute Ischemic Stroke Patients

The Thrombolysis in Cerebral Infarction (TICI) score is an important metric for reperfusion therapy assessment in acute ischemic stroke. It is commonly used as a technical outcome measure after endovascular treatment (EVT). Existing TICI scores are defined in coarse ordinal grades based on visual inspection, leading to inter- and intra-observer variation. In this work, we present autoTICI, an automatic and quantitative TICI scoring method. First, each digital subtraction angiography (DSA) sequence is separated into four phases (non-contrast, arterial, parenchymal and venous phase) using a multi-path convolutional neural network (CNN), which exploits spatio-temporal features. The network also incorporates sequence level label dependencies in the form of a state-transition matrix. Next, a minimum intensity map (MINIP) is computed using the motion corrected arterial and parenchymal frames. On the MINIP image, vessel, perfusion and background pixels are segmented. Finally, we quantify the autoTICI score as the ratio of reperfused pixels after EVT. On a routinely acquired multi-center dataset, the proposed autoTICI shows good correlation with the extended TICI (eTICI) reference with an average area under the curve (AUC) score of 0.81. The AUC score is 0.90 with respect to the dichotomized eTICI. In terms of clinical outcome prediction, we demonstrate that autoTICI is overall comparable to eTICI.Comment: 10 pages; submitted to IEEE TM

Estimating Mutual Information

We present two classes of improved estimators for mutual information $M(X,Y)$, from samples of random points distributed according to some joint probability density $\mu(x,y)$. In contrast to conventional estimators based on binnings, they are based on entropy estimates from $k$-nearest neighbour distances. This means that they are data efficient (with $k=1$ we resolve structures down to the smallest possible scales), adaptive (the resolution is higher where data are more numerous), and have minimal bias. Indeed, the bias of the underlying entropy estimates is mainly due to non-uniformity of the density at the smallest resolved scale, giving typically systematic errors which scale as functions of $k/N$ for $N$ points. Numerically, we find that both families become {\it exact} for independent distributions, i.e. the estimator $\hat M(X,Y)$ vanishes (up to statistical fluctuations) if $\mu(x,y) = \mu(x) \mu(y)$. This holds for all tested marginal distributions and for all dimensions of $x$ and $y$. In addition, we give estimators for redundancies between more than 2 random variables. We compare our algorithms in detail with existing algorithms. Finally, we demonstrate the usefulness of our estimators for assessing the actual independence of components obtained from independent component analysis (ICA), for improving ICA, and for estimating the reliability of blind source separation.Comment: 16 pages, including 18 figure

The Citation Field of Evolutionary Economics

Evolutionary economics has developed into an academic field of its own, institutionalized around, amongst others, the Journal of Evolutionary Economics (JEE). This paper analyzes the way and extent to which evolutionary economics has become an interdisciplinary journal, as its aim was: a journal that is indispensable in the exchange of expert knowledge on topics and using approaches that relate naturally with it. Analyzing citation data for the relevant academic field for the Journal of Evolutionary Economics, we use insights from scientometrics and social network analysis to find that, indeed, the JEE is a central player in this interdisciplinary field aiming mostly at understanding technological and regional dynamics. It does not, however, link firmly with the natural sciences (including biology) nor to management sciences, entrepreneurship, and organization studies. Another journal that could be perceived to have evolutionary acumen, the Journal of Economic Issues, does relate to heterodox economics journals and is relatively more involved in discussing issues of firm and industry organization. The JEE seems most keen to develop theoretical insights

Diagnostic performance of an algorithm for automated large vessel occlusion detection on CT angiography

BACKGROUND: Machine learning algorithms hold the potential to contribute to fast and accurate detection of large vessel occlusion (LVO) in patients with suspected acute ischemic stroke. We assessed the diagnostic performance of an automated LVO detection algorithm on CT angiography (CTA). METHODS: Data from the MR CLEAN Registry and PRESTO were used including patients with and without LVO. CTA data were analyzed by the algorithm for detection and localization of LVO (intracranial internal carotid artery (ICA)/ICA terminus (ICA-T), M1, or M2). Assessments done by expert neuroradiologists were used as reference. Diagnostic performance was assessed for detection of LVO and per occlusion location by means of sensitivity, specificity, and area under the curve (AUC). RESULTS: We analyzed CTAs of 1110 patients from the MR CLEAN Registry (median age (IQR) 71 years (60-80); 584 men; 1110 with LVO) and of 646 patients from PRESTO (median age (IQR) 73 years (62-82); 358 men; 141 with and 505 without LVO). For detection of LVO, the algorithm yielded a sensitivity of 89% in the MR CLEAN Registry and a sensitivity of 72%, specificity of 78%, and AUC of 0.75 in PRESTO. Sensitivity per occlusion location was 88% for ICA/ICA-T, 94% for M1, and 72% for M2 occlusion in the MR CLEAN Registry, and 80% for ICA/ICA-T, 95% for M1, and 49% for M2 occlusion in PRESTO. CONCLUSION: The algorithm provided a high detection rate for proximal LVO, but performance varied significantly by occlusion location. Detection of M2 occlusion needs further improvement

Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophages in the myocardium. Compared to plain liposomes, liposomal clodronate treatment rapidly worsened left ventricular ejection function in hypertensive rats. Liposomal clodronate-treated Ren-2 rat hearts showed areas of myocyte loss with abundant inflammatory cell infiltration, predominantly comprising CD4 positive T lymphocytes. The current-study showed that lack of macrophages vas associated with earlier development of myocardial dysfunction in hypertensive rats. Modulation of macrophage function may be of value in the evolution of cardiomyopath

Clinical and Imaging Determinants of Collateral Status in Patients With Acute Ischemic Stroke in MR CLEAN Trial and Registry

Background and Purpose—Collateral circulation status at baseline is associated with functional outcome after ischemic stroke and effect of endovascular treatment. We aimed to identify clinical and imaging determinants that are associated with collateral grade on baseline computed tomography angiography in patients with acute ischemic stroke due to an anterior circulation large vessel occlusion. Methods—Patients included in the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n=500) and MR CLEAN Registry (n=1488) were studied. Collateral status on baseline computed tomography angiography was scored from 0 (absent) to 3 (good). Multivariable ordinal logistic regression analyses were used to test the association of selected determinants with collateral status. Results—In total, 1988 patients were analyzed. Distribution of the collateral status was as follows: absent (7%, n=123), poor (32%, n=596), moderate (39%, n=735), and good (23%, n=422). Associations for a poor collateral status in a multivariable model existed for age (adjusted common odds ratio, 0.92 per 10 years [95% CI, 0.886–0.98]), male (adjusted common odds ratio, 0.64 [95% CI, 0.53–0.76]), blood glucose level (adjusted common odds ratio, 0.97 [95% CI, 0.95–1.00]), and occlusion of the intracranial segment of the internal carotid artery with occlusion of the terminus (adjusted common odds ratio 0.50 [95% CI, 0.41–0.61]). In contrast to previous studies, we did not find an association between cardiovascular risk factors and collateral status. Conclusions—Older age, male sex, high glucose levels, and intracranial internal carotid artery with occlusion of the terminus occlusions are associated with poor computed tomography angiography collateral grades in patients with acute ischemic stroke eligible for endovascular treatment