Theory, simulation and experimental results of the acoustic detection of magnetization changes in superparamagnetic iron oxide

<p>Abstract</p> <p>Background</p> <p>Magnetic Particle Imaging is a novel method for medical imaging. It can be used to measure the local concentration of a tracer material based on iron oxide nanoparticles. While the resulting images show the distribution of the tracer material in phantoms or anatomic structures of subjects under examination, no information about the tissue is being acquired. To expand Magnetic Particle Imaging into the detection of soft tissue properties, a new method is proposed, which detects acoustic emissions caused by magnetization changes in superparamagnetic iron oxide.</p> <p>Methods</p> <p>Starting from an introduction to the theory of acoustically detected Magnetic Particle Imaging, a comparison to magnetically detected Magnetic Particle Imaging is presented. Furthermore, an experimental setup for the detection of acoustic emissions is described, which consists of the necessary field generating components, i.e. coils and permanent magnets, as well as a calibrated microphone to perform the detection.</p> <p>Results</p> <p>The estimated detection limit of acoustic Magnetic Particle Imaging is comparable to the detection limit of magnetic resonance imaging for iron oxide nanoparticles, whereas both are inferior to the theoretical detection limit for magnetically detected Magnetic Particle Imaging. Sufficient data was acquired to perform a comparison to the simulated data. The experimental results are in agreement with the simulations. The remaining differences can be well explained.</p> <p>Conclusions</p> <p>It was possible to demonstrate the detection of acoustic emissions of magnetic tracer materials in Magnetic Particle Imaging. The processing of acoustic emission in addition to the tracer distribution acquired by magnetic detection might allow for the extraction of mechanical tissue parameters. Such parameters, like for example the velocity of sound and the attenuation caused by the tissue, might also be used to support and improve ultrasound imaging. However, the method can also be used to perform imaging on its own.</p

Testcrosses are an efficient strategy for identifying cis-regulatory variation: Bayesian analysis of allele-specific expression (BayesASE)

Allelic imbalance (AI) occurs when alleles in a diploid individual are differentially expressed and indicates cis acting regulatory variation. What is the distribution of allelic effects in a natural population? Are all alleles the same? Are all alleles distinct? The approach described applies to any technology generating allele-specific sequence counts, for example for chromatin accessibility and can be applied generally including to comparisons between tissues or environments for the same genotype. Tests of allelic effect are generally performed by crossing individuals and comparing expression between alleles directly in the F1. However, a crossing scheme that compares alleles pairwise is a prohibitive cost for more than a handful of alleles as the number of crosses is at least (n2-n)/2 where n is the number of alleles. We show here that a testcross design followed by a hypothesis test of AI between testcrosses can be used to infer differences between nontester alleles, allowing n alleles to be compared with n crosses. Using a mouse data set where both testcrosses and direct comparisons have been performed, we show that the predicted differences between nontester alleles are validated at levels of over 90% when a parent-of-origin effect is present and of 60%-80% overall. Power considerations for a testcross, are similar to those in a reciprocal cross. In all applications, the testing for AI involves several complex bioinformatics steps. BayesASE is a complete bioinformatics pipeline that incorporates state-of-the-art error reduction techniques and a flexible Bayesian approach to estimating AI and formally comparing levels of AI between conditions. The modular structure of BayesASE has been packaged in Galaxy, made available in Nextflow and as a collection of scripts for the SLURM workload manager on github (https://github.com/McIntyre-Lab/BayesASE)

A path forward in the debate over health impacts of endocrine disrupting chemicals

Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate

An Effective Assessment of Simvastatin-Induced Toxicity with NMR-Based Metabonomics Approach

BACKGROUND: Simvastatin, which is used to control elevated cholesterol levels, is one of the most widely prescribed drugs. However, a daily excessive dose can induce drug-toxicity, especially in muscle and liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods of toxicity evaluation are desired. METHODOLOGY/PRINCIPAL FINDINGS: As a new way to evaluate toxicity, we performed NMR-based metabonomics analysis of urine samples. Compared to conventional markers, such as AST, ALT, and CK, the urine metabolic profile provided clearer distinction between the pre- and post-treatment groups treated with toxic levels of simvastatin. Through multivariate statistical analysis, we identified marker metabolites associated with the toxicity. Importantly, we observed that the treatment group could be further categorized into two subgroups based on the NMR profiles: weak toxicity (WT) and high toxicity (HT). The distinction between these two groups was confirmed by the enzyme values and histopathological exams. Time-dependent studies showed that the toxicity at 10 days could be reliably predicted from the metabolic profiles at 6 days. CONCLUSIONS/SIGNIFICANCE: This metabonomics approach may provide a non-invasive and effective way to evaluate the simvastatin-induced toxicity in a manner that can complement current measures. The approach is expected to find broader application in other drug-induced toxicity assessments

Modelling distributions of Aedes aegypti and Aedes albopictus using climate, host density and interspecies competition.

Florida faces the challenge of repeated introduction and autochthonous transmission of arboviruses transmitted by Aedes aegypti and Aedes albopictus. Empirically-based predictive models of the spatial distribution of these species would aid surveillance and vector control efforts. To predict the occurrence and abundance of these species, we fit a mixed-effects zero-inflated negative binomial regression to a mosquito surveillance dataset with records from more than 200,000 trap days, representative of 53% of the land area and ranging from 2004 to 2018 in Florida. We found an asymmetrical competitive interaction between adult populations of Aedes aegypti and Aedes albopictus for the sampled sites. Wind speed was negatively associated with the occurrence and abundance of both vectors. Our model predictions show high accuracy (72.9% to 94.5%) in validation tests leaving out a random 10% subset of sites and data since 2017, suggesting a potential for predicting the distribution of the two Aedes vectors

Die Notverordnungen des kroatischen Präsidenten aus den Jahren 1991 und 1992

U radu se razmatraju uredbe iz nužde koje je donio predsjednik Republike Franjo Tuđman u drugoj polovici 1991. i početkom 1992. godine u vrijeme otvorene agresije na Republiku Hrvatsku. Glavnina uredbi donesena je 10. rujna 1991., a do kraja 1991. godine donesene su gotovo sve uredbe iz nužde. Uredbama su regulirani klasični državni resori poput pravosuđa, unutarnjih poslova i vojske, no velik dio uredbi regulirao je i javne službe te gospodarstvo.At the beginning, this paper gives a brief notional historical overview of emergency decrees, after which follows a reconstruction of events in 1990 that led to the introduction of articles 17 and 101 of the Constitution of the Republic of Croatia as Constitutional decrees relating to states of emergency. The central part of the paper deals with emergency decrees passed by the Croatian President Franjo Tuđman at the time of the open aggression against the Republic of Croatia in the second half of 1991 and the beginning of 1992. In this section, using sources, especially the minutes of the Commission for Constitutional Matters of the Croatian Partliament and the minutes of the plenary sessions of the Croatian Parliament, and also relevant literature, the paper sheds light on the circumstances under which the decrees were passed and approved by the Croatian Parliament, and thus provides a new interpretation of the decrees. After discussing the circumstances under which the decrees were passed, the author deals with various aspects of the decrees\u27 content, first noting the basic characteristics of the decrees, and then classifying them according to fields, such as: internal affairs, defense and justice, and also those covering public services and the economy. While discussing particular decrees the author sets out only the main provisions of the decrees with a view to presenting their basic characteristics, such as the limitation of constitutional rights and the centralisation of public services and of the economy. In the last part of the paper, the author analyzes the constitutionality of the decrees and their lifting. The question of whether the Parliament could convene is paramount in considering the constitutionality of the decrees, since this is important in establishing whether the President of the Republic had the power to pass decrees limiting constitutional rights. The author also considers the decision of the Constitutional Court to approve the constitutionality of the decrees. The lifting of the decrees is analyzed with special consideration given to the circumstances leading to this.Am Anfang dieser Arbeit wird eine kurze begriffshistorische Übersicht über die Notverordnungen präsentiert, wonach rekonstruiert wird, wie die den Ausnahmezustand regelnden Artikel 17 und 101 der Verfassung der Republik Kroatien von 1990 zustande kamen. Der zentrale Teil dieser Arbeit befasst sich mit den Notverordnungen, die der damalige kroatische Staatspräsident Franjo Tuđman während des offenen Angriffskrieges gegen die Republik Kroatien in der zweiten Hälfte des Jahres 1991 und Anfang 1992 erließ. Dabei wird versucht, anhand des Quellenstudiums, vor allem der Niederschriften zur Arbeit der parlamentarischen Kommission für Verfassungsfragen, der Protokolle zu den Plenarsitzungen des Parlaments der Republik Kroatien (Sabor), aber auch unter Rückgriff auf die entsprechende Literatur die Umstände des Erlasses der Notverordnungen sowie ihrer Bestätigung durch den Sabor zu beleuchten und auf diese Weise einen Beitrag zur Reinterpretation der betreffenden Verordnungen zu leisten. Nach einer dementsprechenden Klärung werden die inhaltlichen Aspekte der Verordnungen dargestellt, indem zunächst deren Hauptmerkmale bestimmt werden und danach eine Zuordnung zum Bereich des Inneren, der Verteidigung und der Justiz beziehungsweise zum Bereich der öffentlichen Aufgaben und der Wirtschaft erfolgt. Innerhalb der Darstellung einzelner Verordnungen versuchen wir, lediglich ihre wesentlichen Bestimmungen zu präsentieren, an denen die wichtigsten Merkmale wie die Beschränkung der Verfassungsrechte und die Zentralisierung der öffentlichen Aufgaben und der Wirtschaft deutlich werden. Im letzten Teil der Arbeit werden die Verfassungskonformität der Verordnungen und das Ende ihrer Gültigkeit analysiert. Die Verfassungsmäßigkeit der Verordnungen wird in erster Linie unter dem Aspekt untersucht, ob das Parlament hätte zusammentreten können, wovon schließlich die Zuständigkeit des Präsidenten der Republik für das Erlassen von verfassungsrechtsbeschränkenden Verordnungen abhing. Ebenfalls wird die Entscheidung des Verfassungsgerichts besprochen, in der es den Verordnungen Verfassungsmäßigkeit bescheinigt. Die Aufhebung der Verordnungen wird hinsichtlich der dafür verantwortlichen Umstände analysiert