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\"Coming of age in 1960s Paris, Bernard Appelbaum exists in the hazy shadow of the Holocaust and on the electric cusp of the French New Wave. We find the narrator of Wide awake as he wanders the city streets in search of signs of his father, who was deported by the Nazis in 1942. Bernard's chance encounter with a former acquaintance who has become filmmaker François Truffaut's assistant leads to a spot as an extra on the set of Jules and Jim--setting into motion a series of discoveries and lost memories that crack open a hidden past. On seeing Jules and Jim, Bernard's mother is moved to divulge the secrets of her own past as a Jewish-Polish immigrant to France, which curiously mirrors that of the film's heroine. When revelations about his mother's two loves lead Bernard on a fateful journey through Paris, to Germany, and then to Auschwitz itself, he must plumb haunting depths in order to recover his own identity.\"--Publisher's description.

PurposeRevascularization aims to improve myocardial perfusion. However, changes in regional artery-specific quantitative perfusion after revascularization have not been systematically investigated. It is unclear whether artery-specific thresholds for coronary flow capacity (CFC) and/or relative perfusion predict improved stress perfusion after revascularization. We sought to determine the impact of revascularization based on predefined, artery-specific, severity size thresholds for CFC and/or relative perfusion defects.MethodsFifty patients underwent PET imaging before revascularization and then prospectively within 90 days after revascularization. Changes in regional myocardial blood flow (MBF) were stratified based on baseline perfusion abnormalities, baseline reduced CFC, and whether revascularization was performed in that region.ResultsFollowing angiographic stenosis-directed revascularization, in regions with relative perfusion abnormalities and decreased CFC, stress MBF (sMBF) increased by 0.51 cm3/min/g (59%) from baseline (p < 0.001). In regions without baseline perfusion abnormalities and yet decreased CFC, sMBF increased by 0.35 cm3/min/g (40%) from baseline (p < 0.001). In regions without perfusion abnormalities and normal CFC, sMBF did not increase significantly (+0.07 cm3/min/g, p = 0.56). Patients in whom revascularization was concordant with abnormal PET findings showed increased whole-heart sMBF (+0.22 cm3/min/g, p < 0.001), but in patients in whom revascularization was targeted only to regions without perfusion abnormalities or low CFC, sMBF did not change significantly (−0.06 cm3/min/g, p = 0.38).ConclusionRevascularization targeted to regions with reduced CFC and relative perfusion abnormalities on baseline PET yielded significant improvements in sMBF. When revascularization was performed in regions without reduced CFC, sMBF did not improve.

BackgroundComposite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference “truth” to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS.ResultsMedian rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52–1.02] and 0.16 with 4DM; 0.41 [0.34–0.54] and 0.10 with 4DM-FVD; 0.66 [0.51–0.85] and 0.11 with Cedars; 0.51 [0.43–0.61] and 0.08 with Emory-Votaw; 0.37 [0.30–0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23–0.32], COV 0.07 with HeartSee.ConclusionsSWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively).Trial registration: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593.

We examined whether regional improvement in stress myocardial blood flow (sMBF) following angiography-guided coronary revascularization depends on the existence of a perfusion defect on positron emission tomography (PET). Percent stenosis on coronary angiography often is the main factor when deciding whether to perform revascularization, but it does not reliably relate to maximum sMBF. PET is a validated method of assessing sMBF. 19 patients (79% M, 65 ± 12 years) underwent PET stress before and after revascularization (17 PCI, 2 CABG). Pre- and post-revascularization sMBF for each left ventricular quadrant (anterior, septal, lateral, and inferior) was stratified by the presence or absence of a baseline perfusion defect on PET and whether that region was revascularized. Intervention was performed on 40 of 76 quadrants. When a baseline perfusion defect existed in a region that was revascularized (n = 26), post-revascularization flow increased by 0.6 ± 0.7 cc/min/g (1.2 ± 0.4 vs 1.7 ± 0.8, P < 0.001). When no defect existed but revascularization was performed (n = 14), sMBF did not change significantly (1.7 ± 0.3 vs 1.5 ± 0.4 cc/min/g, P = 0.16). In regions without a defect that were not revascularized (n = 29), sMBF did not significantly change (2.0 ± 0.6 vs 1.9 ± 0.7, P = 0.7). When a stress-induced perfusion defect exists on PET, revascularization improves sMBF in that region. When there is no such defect, sMBF shows no net change, whether or not intervention is performed in that area. PET stress may be useful for identifying areas of myocardium that could benefit from revascularization, and also areas in which intervention is unlikely to yield improvement in myocardial blood flow.

In stable coronary artery disease (CAD), reduction in mortality and/or myocardial infarction with revascularization over medical therapy has not been reliably achieved. Coronary arteries are usually extracted to perform stenosis detection. We aim to develop an automatic algorithm by deep learning to extract coronary arteries from ICAs.In this study, a multi-input and multi-scale (MIMS) U-Net with a two-stage recurrent training strategy was proposed for the automatic vessel segmentation. Incorporating features such as the Inception residual module with depth-wise separable convolutional layers, the proposed model generated a refined prediction map with the following two training stages: (i) Stage I coarsely segmented the major coronary arteries from pre-processed single-channel ICAs and generated the probability map of vessels; (ii) during the Stage II, a three-channel image consisting of the original preprocessed image, a generated probability map, and an edge-enhanced image generated from the preprocessed image was fed to the proposed MIMS U-Net to produce the final segmentation probability map. During the training stage, the probability maps were iteratively and recurrently updated by feeding into the neural network. After segmentation, an arterial stenosis detection algorithm was developed to extract vascular centerlines and calculate arterial diameters to evaluate stenotic level. Experimental results demonstrated that the proposed method achieved an average Dice score of 0.8329, an average sensitivity of 0.8281, and an average specificity of 0.9979 in our dataset with 294 ICAs obtained from 73 patient. Moreover, our stenosis detection algorithm achieved a true positive rate of 0.6668 and a positive predictive value of 0.7043.

Background. Percutaneous coronary intervention(PCI) in stable coronary artery disease(CAD) is commonly triggered by abnormal myocardial perfusion imaging(MPI). However, due to the possibilities of multivessel disease and variability of coronary artery perfusion distribution, opportunity exists to better align anatomic stenosis with perfusion abnormalities to improve revascularization decisions. This study aims to develop a 3D multi-modality fusion approach to assist decision-making for PCI. Methods. Coronary arteries from fluoroscopic angiography(FA) were reconstructed into 3D artery anatomy. Left ventricular(LV) epicardial surface was extracted from SPECT. The 3D artery anatomy was non-rigidly fused with the LV epicardial surface. The accuracy of the 3D fusion was evaluated via both computer simulation and real patient data. For technical validation, simulated FA and MPI were integrated and then compared with the ground truth from a digital phantom. For clinical validation, FA and SPECT images were integrated and then compared with the ground truth from CT angiograms. Results. In the technical evaluation, the distance-based mismatch error between simulated fluoroscopy and phantom arteries is 1.86(SD:1.43)mm for left coronary arteries(LCA) and 2.21(SD:2.50)mm for right coronary arteries(RCA). In the clinical validation, the distance-based mismatch errors between the fluoroscopy and CT arteries were 3.84(SD:3.15)mm for LCA and 5.55(SD:3.64)mm for RCA. The presence of the corresponding fluoroscopy and CT arteries in the AHA 17-segment model agreed well with a Kappa value of 0.91(95% CI: 0.89-0.93) for LCA and 0.80(CI: 0.67-0.92) for RCA. Conclusions. Our fusion approach is technically accurate to assist PCI decision-making and is clinically feasible to be used in the catheterization laboratory. There is an opportunity to improve the decision-making and outcomes of PCI in stable CAD.

Young Woodrow Wilson examines the early life of Thomas Woodrow Wilson. Central to the theme of this study is what Woodrow Wilson himself termed his \"inner history.\" This biography concerns itself with the development of Woodrow Wilson's personality within the context of his familial, social, and cultural milieu and their effect upon his political philosophy and lifework. The methodology employed is holistic, dynamic and functional rather than atomistic, static and taxonomic. This study then explores the interpenetration of Woodrow Wilson with his world. Woodrow Wilson was the first son and favorite child of Joseph and Janet Wilson. Joseph who never achieved in life all he desired passed this burden of insatiable achievement to his son. Woodrow failed to meet his father's high standards. Like his mother, Woodrow suffered from congenital developmental dyslexia which as bi-hemisphere spatial representation interfered with the analytic, cognitive strategy necessary to read English. Joseph who taught his son in the only manner he knew reinforced Woodrow's communicative emotional deprivations. Janet's response was to protect her son from Joseph and everyone else who might criticize him. Woodrow Wilson was fond of expressing the belief that now and then in history there are born men of such individuality that they command their own development. For Woodrow Wilson, this was necessity. Though the influence of his parents was strong, Wilson's own decisions were the decisive ones of his life. In his growth from childhood through adolescence, Woodrow Wilson continued to integrate his own identity with an ever increasing social awareness. Having had to struggle for his autonomy and identity against a father he intensely admired, Woodrow developed his version of familial politics. These familial struggles later served to form an embryonic understanding of the South in the Civil War and Reconstruction. In this way, Wilson's interior world mirrored his social environment. Having daily before his eyes, the results of ideas, emotions and actions driven to a frenzy, Wilson began to create in response a personal and political philosophy which gave order and purpose to his life. The philosophy Wilson espoused stressed the necessity of slow, deliberate change, one extremely historical and non-metaphysical. By the time Woodrow left home for the college life of Princeton, he was becoming increasingly detached from the ministerial career his father had chosen for him. Religion never became a convenantal metaphysics. From Princeton onward, Woodrow Wilson sought his heroic immortality in the secular city. At the age of thirty-three, Woodrow confided to his diary the desire to have his age's political autobiography written through his life. In this, he not only placed himself within the evolutionary naturalism of his time, but he sought as well to transcend his personal history through some immortal work.

In this study of perinatal and infantile hypophosphatasia, patients received ENB-0040, a bone-targeted, recombinant, human tissue-nonspecific isozyme of alkaline phosphatase that is lacking in this disease. Rickets healed, and developmental milestones and pulmonary function improved. Hypophosphatasia is the inborn error of metabolism that is characterized by low serum alkaline-phosphatase activity from loss-of-function mutations, typically missense, within the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). 1 Natural substrates of TNSALP that accumulate in hypophosphatasia include inorganic pyrophosphate, 2 an inhibitor of mineralization, 3 and pyridoxal 5′-phosphate (PLP), the principal circulating form of vitamin B 6 . 4 High extracellular levels of inorganic pyrophosphate block hydroxyapatite crystal growth 3 , 5 and cause rickets or osteomalacia. Hypercalcemia and hyperphosphatemia can develop in severely affected patients. 1 The deranged vitamin B 6 metabolism shows that TNSALP functions as a cell-surface enzyme 6 and explains . . .

Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS IVA was treated with HSCT at 15 years of age and followed up for 10 years. Radiographs showed that the figures of major and minor trochanter appeared. Loud snoring and apnea disappeared. In all, 1 year after bone marrow transplantation, bone mineral density at L2-L4 was increased from 0.372 g/cm(2) to 0.548 g/cm(2) and was maintained at a level of 0.48±0.054 for the following 9 years. Pulmonary vital capacity increased approximately 20% from a baseline of 1.08 L to around 1.31 L over the first 2 years and was maintained thereafter. Activity of daily living was improved similar to the normal control group. After bilateral osteotomies, a patient can walk over 400 m using hip-knee-ankle-foot orthoses. This long-term observation of a patient shows that this treatment can produce clinical improvements although bone deformity remained unchanged. In conclusion, ERT is a therapeutic option for MPS IVA patients, and there are some indications that HSCT may be an alternative to treat this disease. However, as neither seems to be a curative therapy, at least for the skeletal dysplasia in MPS IVA patients, new approaches are investigated to enhance efficacy and reduce costs to benefit MPS IVA patients.

Polypyrrole (PPy) in globular form and as nanotubes were prepared by the oxidation of pyrrole with iron(III) chloride in the absence and presence of methyl orange, respectively. They were subsequently converted to nitrogen-containing carbons at 650 °C in an inert atmosphere. The course of carbonization was followed by thermogravimetric analysis and the accompanying changes in molecular structure by Fourier Transform Infrared and Raman spectroscopies. Both the original and carbonized materials have been tested in sensing of polar and non-polar organic vapors. The resistivity of sensing element using globular PPy was too high and only nanotubular PPy could be used. The sensitivity of the PPy nanotubes to ethanol vapors was nearly on the same level as that of their carbonized analogs (i.e., ~18% and 24%, respectively). Surprisingly, there was a high sensitivity of PPy nanotubes to the n-heptane vapors (~110%), while that of their carbonized analog remained at ~20%. The recovery process was significantly faster for carbonized PPy nanotubes (in order of seconds) compared with 10 s of seconds for original nanotubes, respectively, due to higher specific surface area after carbonization.