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"Christen, Thomas"
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الكنز المرصود في قواعد التلمود
يعتبر هذا الكتاب هو المرجع الأساسي في كل طباع اليهود وأفعالهم ويبين أن اليهود عندهم كتاب مقدس هو التوراة وفيه أحكام فقهية وضعوا لها تفسيرا ووضعوا هذا التفسير في كتاب أسموه بالتلمود وهو مكون من متن وشرح والمتن يسمى بالمشنا والشرح يسمى بالجمارا وفي أثناء الشرح وضعوا الكلام الذي يدل على أن جميع الأمم يحل لليهود سفك دمائهم ولأنهم يعتقدون ذلك كانوا يسرقون الأولاد و يستنزفون دماءهم ليعجنوا به فطير الفصح وقد سجل المؤرخون عليهم بالوثائق الرسمية هذا الفعل الشائن وسجل القرآن على اليهود أنهم قتلوا أولادهم سفها بغير علم وفي الزبورالمائة والسادس أن اليهود ذبحوا بنيهم وبناتهم للأصنام وسفكوا الدماء الزكية.
BOOK
Streamlined magnetic resonance fingerprinting: Fast whole-brain coverage with deep-learning based parameter estimation
Magnetic resonance fingerprinting (MRF) is a quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current challenges exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. This study aims to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1+ correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm3 and 1.7×1.7×3 mm3, and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R = 1–1.04, R2>0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R2>0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4 ± 0.4%, 3.6 ± 0.3% and 6.0 ± 0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation.
Journal Article
Simultaneous Perfusion and Permeability Measurements Using Combined Spin- and Gradient-Echo MRI
The purpose of this study was to estimate magnetic resonance imaging-based brain perfusion parameters from combined multiecho spin-echo and gradient-echo acquisitions, to correct them for T1-, T2-, and T∗2-related contrast agent (CA) extravasation effects, and to simultaneously determine vascular permeability. Perfusion data were acquired using a combined multiecho spin- and gradient-echo (SAGE) echo-planar imaging sequence, which was corrected for CA extravasation effects using pharmacokinetic modeling. The presented method was validated in simulations and brain tumor patients, and compared with uncorrected single-echo and multiecho data. In the presence of CA extravasation, uncorrected single-echo data resulted in underestimated CA concentrations, leading to underestimated single-echo cerebral blood volume (CBV) and mean transit time (MTT). In contrast, uncorrected multiecho data resulted in overestimations of CA concentrations, CBV, and MTT. The correction of CA extravasation effects resulted in CBV and MTT estimates that were more consistent with the underlying tissue characteristics. Spin-echo perfusion data showed reduced large-vessel blooming effects, facilitating better distinction between increased CBV due to active tumor progression and elevated CBV due to the presence of cortical vessels in tumor proximity. Furthermore, extracted permeability parameters were in good agreement with elevated T1-weighted postcontrast signal values.
Journal Article
MP3: Medical Software for Processing Multi-Parametric Images Pipelines
This article presents an open source software able to convert, display and process medical images. It differentiates itself from the existing software by its ability to design complex processing pipelines and to wisely execute them on a large database. An MP3 pipeline can contain unlimited homemade or ready-made processes and can be carried out with a parallel execution system. As a viewer, MP3 allows to display up to 4 images together and to draw Regions Of Interest (ROI). Two applications showing the strengths of the software are here exposed: a preclinical study involving Magnetic Resonance Imaging (MRI) data and a clinical one involving Computed Tomography (CT) images. MP3 is downloadable at https://github.com/nifm-gin/MP3.
Journal Article
Rationale and design of the EVOLVE Short DAPT Study to assess 3-month dual antiplatelet therapy in subjects at high risk for bleeding undergoing percutaneous coronary intervention
While extended dual antiplatelet therapy (DAPT) with aspirin and a platelet (P2Y12) inhibitor after percutaneous coronary intervention (PCI) reduces the risk of stent thrombosis (ST) and myocardial infarction (MI), it also increases bleeding. Newer generation drug-eluting stents with bioabsorbable polymer coatings may reduce thrombotic events and allow abbreviated DAPT in selected patients. The EVOLVE Short DAPT study is designed to evaluate the safety of 3-month DAPT in high bleeding risk subjects treated with the SYNERGY bioabsorbable polymer everolimus-eluting stent.
EVOLVE Short DAPT is a prospective, single-arm, international study that enrolled 2009 high risk bleeding subjects (defined as age ≥75 years, chronic anticoagulation, major bleeding within 12 months, history of stroke, renal insufficiency/failure, or thrombocytopenia) who underwent PCI with the SYNERGY stent. Subjects presenting with acute MI or complex lesions were excluded. After 3 months treatment with DAPT (except those on anticoagulant in whom aspirin is optional), subjects free from stroke, MI, revascularization or ST will be eligible to discontinue P2Y12 inhibitor, but continue aspirin. Co-primary endpoints assessed between 3–15 months are: i) death/MI compared for non-inferiority with propensity-adjusted historical group receiving 12-month DAPT, and ii) definite/probable ST compared to a performance goal. The secondary endpoint is the rate of bleeding in subjects not receiving chronic anticoagulation compared for superiority against a propensity-adjusted historical control.
The EVOLVE Short DAPT study will prospectively define the safety of DAPT discontinuation at 3 months in high bleeding risk patients treated with the SYNERGY stent.
Journal Article
Contrast-enhanced functional blood volume imaging (CE-fBVI): Enhanced sensitivity for brain activation in humans using the ultrasmall superparamagnetic iron oxide agent ferumoxytol
Functional MRI (fMRI) brain studies performed in the presence of a steady-state or “blood pool” contrast agent yields activation maps that are weighted for cerebral blood volume (CBV). Previous animal experiments suggest significant contrast-to-noise ratio (CNR) improvements, but these studies have not yet been performed in humans due to the lack of availability of a suitable agent. Here we report the use of the USPIO ferumoxytol (AMAG Pharmaceuticals, Inc., Cambridge, MA) for functional brain activation in humans, termed contrast enhanced functional blood volume imaging (CE-fBVI). Four subjects were scanned during a unilateral finger tapping task with standard blood–oxygen level dependent (BOLD) imaging before contrast and CE-fBVI after contrast injection. The CE-fBVI response showed both a fast (5.8±1.3s) and a slow (75.3±27.5s) component of CBV response to stimuli. A significant CNR gain of approximately 2–3 was found for CE-fBVI compared to BOLD fMRI. Interestingly, less susceptibility-related signal dropouts were observed in the inferior frontal and temporal lobes with CE-fBVI. The combination of higher CNR and better spatial specificity, enabled by CE-fBVI using blood pool USPIO contrast agent opens the door to higher resolution brain mapping.
► First report of the use of USPIO for functional brain activation in humans. ► The method is sensitive to blood volume changes and is termed CE-fBVI. ► A significant CNR gain of about 2-3 was found for CE-fBVI compared to BOLD fMRI. ► Less susceptibility-related signal dropout was found with CE-fBVI. ► Time response of CE-fBVI to stimuli was characterized.
Journal Article
Modeling Electric Discharges with Entropy Production Rate Principles
Under which circumstances are variational principles based on entropy production rate useful tools for modeling steady states of electric (gas) discharge systems far from equilibrium? It is first shown how various different approaches, as Steenbeck’s minimum voltage and Prigogine’s minimum entropy production rate principles are related to the maximum entropy production rate principle (MEPP). Secondly, three typical examples are discussed, which provide a certain insight in the structure of the models that are candidates for MEPP application. It is then thirdly argued that MEPP, although not being an exact physical law, may provide reasonable model parameter estimates, provided the constraints contain the relevant (nonlinear) physical effects and the parameters to be determined are related to disregarded weak constraints that affect mainly global entropy production. Finally, it is additionally conjectured that a further reason for the success of MEPP in certain far from equilibrium systems might be based on a hidden linearity of the underlying kinetic equation(s).
Journal Article
Connexin37 protects against atherosclerosis by regulating monocyte adhesion
A genetic polymorphism in the human gene encoding connexin37 (CX37, encoded by
GJA4
, also known as
CX37
) has been reported as a potential prognostic marker for atherosclerosis
1
. The expression of this gap-junction protein is altered in mouse and human atherosclerotic lesions
2
: it disappears from the endothelium of advanced plaques but is detected in macrophages recruited to the lesions. The role of CX37 in atherogenesis, however, remains unknown. Here we have investigated the effect of deleting the mouse connexin37 (Cx37) gene (
Gja4
, also known as
Cx37
) on atherosclerosis in apolipoprotein E–deficient (
Apoe
−/−
) mice, an animal model of this disease
3
. We find that
Gja4
−/−
Apoe
−/−
mice develop more aortic lesions than
Gja4
+/+
Apoe
−/−
mice that express Cx37. Using
in vivo
adoptive transfer, we show that monocyte and macrophage recruitment is enhanced by eliminating expression of Cx37 in these leukocytes but not by eliminating its expression in the endothelium. We further show that Cx37 hemichannel activity in primary monocytes, macrophages and a macrophage cell line (H36.12j) inhibits leukocyte adhesion. This antiadhesive effect is mediated by release of ATP into the extracellular space. Thus, Cx37 hemichannels may control initiation of the development of atherosclerotic plaques by regulating monocyte adhesion. H36.12j macrophages expressing either of the two CX37 proteins encoded by a polymorphism in the human
GJA4
gene show differential ATP-dependent adhesion. These results provide a potential mechanism by which a polymorphism in CX37 protects against atherosclerosis.
Journal Article
Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing evaluation: Rationale and best practices. A report from the cardiac safety research consortium
This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled “The Role of Endpoint Adjudication in Medical Device Clinical Trials”. The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence.
Journal Article
Spontaneous BOLD Signal Fluctuations in Young Healthy Subjects and Elderly Patients with Chronic Kidney Disease
Spontaneous fluctuations in blood oxygenation level-dependent (BOLD) images are the basis of resting-state fMRI and frequently used for functional connectivity studies. However, there may be intrinsic information in the amplitudes of these fluctuations. We investigated the possibility of using the amplitude of spontaneous BOLD signal fluctuations as a biomarker for cerebral vasomotor reactivity. We compared the coefficient of variation (CV) of the time series (defined as the temporal standard deviation of the time series divided by the mean signal intensity) in two populations: 1) Ten young healthy adults and 2) Ten hypertensive elderly subjects with chronic kidney disease (CKD). We found a statistically significant increase (P<0.01) in the CV values for the CKD patients compared with the young healthy adults in both gray matter (GM) and white matter (WM). The difference was independent of the exact segmentation method, became more significant after correcting for physiological signals using RETROICOR, and mainly arose from very low frequency components of the BOLD signal fluctuation (f<0.025 Hz). Furthermore, there was a strong relationship between WM and GM signal fluctuation CV's (R(2)= 0.87) in individuals, with a ratio of about 1:3. These results suggest that amplitude of the spontaneous BOLD signal fluctuations may be used to assess the cerebrovascular reactivity mechanisms and provide valuable information about variations with age and different disease states.
Journal Article