Guiding of keV ions between two insulating parallel plates.

Experimental data are presented for low-energy singly charged ion transport between two insulating parallel plates. Using a beam intensity of approximately 20 pA, measurements of the incoming and transmitted beams provide quantitative temporal information about the charge deposited on the plates and the guiding probability. Using a smaller beam intensity (~ 1 pA) plate charging and discharging properties were studied as a function of time. These data imply that both the charge deposition and decay along the surface and through the bulk need to be modeled as acting independently. A further reduction of beam intensity to ~ 25 fA allowed temporal imaging studies of the positions and intensities of the guided beam plus two bypass beams to be performed. SIMION software was used to simulate trajectories of the guided and bypass beams, to provide information about the amount and location of deposited charge and, as a function of charge patch voltage, the probability of beam guiding and how much the bypass beams are deflected plus to provide information about the electric fields. An equivalent electric circuit model of the parallel plates, used to associate the deposited charge with the patch voltage implies that the deposited charge is distributed primarily on the inner surface of the plates, transverse to the beam direction, rather than being distributed throughout the entire plate.

Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

Magnetic Resonance Imaging and Bioluminescence Imaging for Evaluating Tumor Burden in Orthotopic Colon Cancer.

Quantifying tumor burden is important for following the natural history of orthotopic colon cancer and therapeutic efficacy. Bioluminescence imaging (BLI) is commonly used for such assessment and has both advantages and limitations. We compared BLI and magnetic resonance imaging (MRI) for quantifying orthotopic tumors in a mouse model of colon cancer. Among sequences tested, T2-based MRI imaging ranked best overall for colon cancer border delineation, contrast, and conspicuity. Longitudinal MRI detected tumor outside the colon, indistinguished by BLI. Colon tumor weights calculated from MRI in vivo correlated highly with tumor weights measured ex vivo whereas the BLI signal intensities correlated relatively poorly and this difference in correlations was highly significant. This suggests that MRI may more accurately assess tumor burden in longitudinal monitoring of orthotopic colon cancer in this model as well as in other models.

An unexpected asymptomatic epiglottal site of Kimura disease.

INTRODUCTION: Kimura disease (KD) is a chronic lymphoproliferative disorder of unknown etiology that affects the skin and lymph nodes, mostly observed in males of Asian descent. The natural history of asymptomatic epiglottal KD remains unknown. This rare site of KD is often only diagnosed when tumor growth starts to obstruct the upper airways. OBSERVATION: A 34-year-old North African male presented with fatigue and multiple, slowly progressive, fluctuating skin nodules in the right mandibular and retroauricular regions. Computed tomography of the head and neck revealed a large soft tissue tumor close to the right mandibular body and unexpected thickening of the epiglottis. Transnasal laryngoscopy confirmed the CT findings and showed thickening of the epiglottis. The diagnosis of KD was based on histological examination of biopsy specimens taken from the right mandibular tumor, a cervical lymph node, and the epiglottis. DISCUSSION: Most cases of KD with epiglottal involvement present with dysphonia and dysphagia. No consensus guidelines are available concerning the complementary investigations that should be performed. This case report raises the question of whether patients with suspected KD should be systematically screened for lesions in unusual and potentially dangerous anatomic sites.

Effects of Interpolation on the Inverse Problem of Electrocardiography.

Electrocardiographic Imaging (ECGI) aims to reconstruct electrograms from the body surface potential measurements. Bad leads are usually excluded from the inverse problem solution. Alternatively, interpolation can be applied. This study explores how sensitive ECGI is to different bad-lead configurations and interpolation methods. Experimental data from a Langendorff-perfused pig heart suspended in a human-shaped torso-tank was used. Epicardial electrograms were acquired during 30 s (31 beats) of RV pacing using a 108-electrode array, simultaneously with torso potentials from 128 electrodes embedded in the tank surface. Six different bad lead cases were designed based on clinical experience. Inverse problem was solved by applying Tikhonov regularization i) using the complete data, ii) bad-leads-removed data, and iii) interpolated data, with 5 different methods. Our results showed that ECGI accuracy of an interpolation method highly depends on the location of the bad leads. If they are in the high-potential-gradient regions of the torso, a highly accurate interpolation method is needed to achieve an ECGI accuracy close to using complete data. If the BSP reconstruction of the interpolation method is poor in these regions, the reconstructed electrograms also have lower accuracy, suggesting that bad leads should be removed instead of interpolated. The inverse-forward method was found to be the best among all interpolation methods applied in this study in terms of both missing BSP lead reconstruction and ECGI accuracy, even for the bad leads located over the chest.

TTC7A mutation must be considered in patients with repeated intestinal atresia associated with early inflammatory bowel disease: Two new case reports and a literature review.

TTC7A mutations cause multiple neonatal intestinal atresias with early inflammatory bowel disease and severe combined immunodeficiency. There are no treatment protocols for this rare disease. Two new cases are described for which radical early treatment measures - total enterectomy, home parenteral nutrition, immunoglobulin therapy and intravenous antibiotic prophylaxis - have allowed both patients to develop optimally.

Reduction of Effects of Noise on the Inverse Problem of Electrocardiography with Bayesian Estimation.

To overcome the ill-posed nature of the inverse problem of electrocardiography (ECG) and stabilize the solutions, regularization is used. Despite several studies on noise, effect of prefiltering of ECG signals on the regularized inverse solutions has not been explored. We used Bayesian estimation for solving the inverse ECG problem with and without applying various prefiltering methods, and evaluated our results using experimental data that came from a Langendorff-perfused pig heart suspended in a human-shaped torso-tank. Epicardial electrograms were recorded during RV pacing using a 108-electrode array, simultaneously with ECGs from 128 electrodes embedded in the tank surface. Leave-one-beat-out protocol was used to obtain the prior probability density function (pdf) of electro-grams and noise statistics. Noise pdf was assumed to be zero mean-Gaussian, with covariance assumptions: a) independent and identically distributed (noi-iid), b) correlated (noi-corr). Reconstructed electrograms and activation times were compared to those directly recorded by the sock for 3 beats selected from the recording. Noi-corr is superior to noi-iid when the training set is a good match to data, but for applications requiring activation time derivation, careful selection of preprocessing methods, in particular to adequately remove high-frequency noise, and an appropriate noise model is needed.

Effects of ECG Signal Processing on the Inverse Problem of Electrocardiography.

The inverse problem of electrocardiography is ill-posed. Errors in the model such as signal noise can impact the accuracy of reconstructed cardiac electrical activity. It is currently not known how sensitive the inverse problem is to signal processing techniques. To evaluate this, experimental data from a Langendorff-perfused pig heart (n=1) suspended in a human-shaped torso-tank was used. Different signal processing methods were applied to torso potentials recorded from 128 electrodes embedded in the tank surface. Processing methods were divided into three categories i) high-frequency noise removal ii) baseline drift removal and iii) signal averaging, culminating in n=72 different signal sets. For each signal set, the inverse problem was solved and reconstructed signals were compared to those directly recorded by the sock around the heart. ECG signal processing methods had a dramatic effect on reconstruction accuracy. In particular, removal of baseline drift significantly impacts the magnitude of reconstructed electrograms, while the presence of high-frequency noise impacts the activation time derived from these signals (p<0.05).

ARIES: Enabling Visual Exploration and Organization of Art Image Collections.

Art historians have traditionally used physical light boxes to prepare exhibits or curate collections. On a light box, they can place slides or printed images, move the images around at will, group them as desired, and visual-ly compare them. The transition to digital images has rendered this workflow obsolete. Now, art historians lack well-designed, unified interactive software tools that effectively support the operations they perform with physi-cal light boxes. To address this problem, we designed ARIES (ARt Image Exploration Space), an interactive image manipulation system that enables the exploration and organization of fine digital art. The system allows images to be compared in multiple ways, offering dynamic overlays analogous to a physical light box, and sup-porting advanced image comparisons and feature-matching functions, available through computational image processing. We demonstrate the effectiveness of our system to support art historians tasks through real use cases.

Early B-cell-specific inactivation of ATM synergizes with ectopic CyclinD1 expression to promote pre-germinal center B-cell lymphomas in mice.

Ataxia telangiectasia-mutated (ATM) kinase is a master regulator of the DNA damage response. ATM is frequently inactivated in human B-cell non-Hodgkin lymphomas, including ~50% of mantle cell lymphomas (MCLs) characterized by ectopic expression of CyclinD1. Here we report that early and robust deletion of ATM in precursor/progenitor B cells causes cell autonomous, clonal mature B-cell lymphomas of both pre- and post-germinal center (GC) origins. Unexpectedly, naive B-cell-specific deletion of ATM is not sufficient to induce lymphomas in mice, highlighting the important tumor suppressor function of ATM in immature B cells. Although EµCyclinD1 is not sufficient to induce lymphomas, EµCyclinD1 accelerates the kinetics and increases the incidence of clonal lymphomas in ATM-deficient B-cells and skews the lymphomas toward pre-GC-derived small lymphocytic neoplasms, sharing morphological features of human MCL. This is in part due to CyclinD1-driven expansion of ATM-deficient naive B cells with genomic instability, which promotes the deletions of additional tumor suppressor genes (i.e. Trp53, Mll2, Rb1 and Cdkn2a). Together these findings define a synergistic function of ATM and CyclinD1 in pre-GC B-cell proliferation and lymphomagenesis and provide a prototypic animal model to study the pathogenesis of human MCL.

Minimally invasive repair of pectus excavatum using the Nuss technique in children and adolescents: indications, outcomes, and limitations.

BACKGROUND: Pectus excavatum (PE) is a common congenital deformity. The Nuss technique for minimally invasive repair of PE involves thoracoscopy-assisted insertion of a bar or plate behind the deformity to displace the sternum anteriorly. Our objective here was to clarify the indications and limitations of the Nuss technique based on a review of 70 patients. MATERIALS AND METHODS: A retrospective review of children managed at two centres identified 70 patients who had completed their growth and had their plate removed. Mean age was 13.8 years (range, 6-19 years). The reason for surgery was cosmetic disfigurement in 66 (95%) patients. The original Nuss technique was used in 63 patients, whereas 7 patients required an additional sub-xiphoid approach. Time to implant removal ranged from 8 months to 3 years. RESULTS: The cosmetic outcome was considered satisfactory by the patients in 64 (91%) cases and by the surgeon in 60 (85.7%) cases. Major complications requiring further surgery occurred in 6 (8.5%) patients and consisted of haemothorax (n=2), chest wall sepsis (n=2, including 1 after implant removal), allergy (n=1), and implant displacement (n=1). Early or delayed minor complications occurred in 46 (65%) patients and resolved either spontaneously or after non-surgical therapy. DISCUSSION: The minimal scarring and reliably good outcomes support the widespread use of the Nuss technique in children and adolescents. Our complication rates (minor, 65%; and major, 8.5%) are consistent with previous publications. In our opinion, contra-indications to thoracoscopic PE correction consist of a history of cardio-thoracic surgery and the finding by computed tomography of a sternum-to-spine distance of less than 5 cm or of sternum rotation greater than 35°. In these situations, we recommend a sub- and retro-xiphoid approach to guide implant insertion or a classic sterno-chondroplasty procedure. LEVEL OF EVIDENCE: Level IV, retrospective descriptive cohort study.

Electron- and proton-impact excitation of hydrogenlike uranium in relativistic collisions.

The K shell excitation of H-like uranium (U(91+)) in relativistic collisions with different gaseous targets has been studied at the experimental storage ring at GSI Darmstadt. By performing measurements with different targets as well as with different collision energies, we were able to observe for the first time the effect of electron-impact excitation (EIE) process in the heaviest hydrogenlike ion. The large fine-structure splitting in H-like uranium allowed us to unambiguously resolve excitation into different L shell levels. State-of-the-art calculations performed within the relativistic framework which include excitation mechanisms due to both protons (nucleus) and electrons are in good agreement with the experimental findings. Moreover, our experimental data clearly demonstrate the importance of including the generalized Breit interaction in the treatment of the EIE process.

Binary millisecond pulsar discovery via gamma-ray pulsations.

Millisecond pulsars, old neutron stars spun up by accreting matter from a companion star, can reach high rotation rates of hundreds of revolutions per second. Until now, all such "recycled" rotation-powered pulsars have been detected by their spin-modulated radio emission. In a computing-intensive blind search of gamma-ray data from the Fermi Large Area Telescope (with partial constraints from optical data), we detected a 2.5-millisecond pulsar, PSR J1311-3430. This unambiguously explains a formerly unidentified gamma-ray source that had been a decade-long enigma, confirming previous conjectures. The pulsar is in a circular orbit with an orbital period of only 93 minutes, the shortest of any spin-powered pulsar binary ever found.

Polarization transfer of bremsstrahlung arising from spin-polarized electrons.

We report on a study of the polarization transfer between transversely polarized incident electrons and the emitted x rays for electron-atom bremsstrahlung. By means of Compton polarimetry we performed for the first time an energy-differential measurement of the complete properties of bremsstrahlung emission related to linear polarization, i.e., the degree of linear polarization as well as the orientation of the polarization axis. For the high-energy end of the bremsstrahlung continuum the experimental results for both observables show a high sensitivity on the initial electron spin polarization and prove that the polarization orientation is virtually independent of the photon energy.

Periodic emission from the gamma-ray binary 1FGL J1018.6-5856.

Gamma-ray binaries are stellar systems containing a neutron star or black hole, with gamma-ray emission produced by an interaction between the components. These systems are rare, even though binary evolution models predict dozens in our Galaxy. A search for gamma-ray binaries with the Fermi Large Area Telescope (LAT) shows that 1FGL J1018.6-5856 exhibits intensity and spectral modulation with a 16.6-day period. We identified a variable x-ray counterpart, which shows a sharp maximum coinciding with maximum gamma-ray emission, as well as an O6V((f)) star optical counterpart and a radio counterpart that is also apparently modulated on the orbital period. 1FGL J1018.6-5856 is thus a gamma-ray binary, and its detection suggests the presence of other fainter binaries in the Galaxy.

Peroxisome proliferator-activated receptor δ confers resistance to peroxisome proliferator-activated receptor γ-induced apoptosis in colorectal cancer cells.

Peroxisome proliferator-activated receptor γ (PPARγ) may serve as a useful target for drug development in non-diabetic diseases. However, some colorectal cancer cells are resistant to PPARγ agonists by mechanisms that are poorly understood. Here, we provide the first evidence that elevated PPARδ expression and/or activation of PPARδ antagonize the ability of PPARγ to induce colorectal carcinoma cell death. More importantly, the opposing effects of PPARδ and PPARγ in regulating programmed cell death are mediated by survivin and caspase-3. We found that activation of PPARγ results in decreased survivin expression and increased caspase-3 activity, whereas activation of PPARδ counteracts these effects. Our findings suggest that PPARδ and PPARγ coordinately regulate cancer cell fate by controlling the balance between the cell death and survival and demonstrate that inhibition of PPARδ can reprogram PPARγ ligand-resistant cells to respond to PPARγ agonists.

Gamma-ray flares from the Crab Nebula.

A young and energetic pulsar powers the well-known Crab Nebula. Here, we describe two separate gamma-ray (photon energy greater than 100 mega-electron volts) flares from this source detected by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. The first flare occurred in February 2009 and lasted approximately 16 days. The second flare was detected in September 2010 and lasted approximately 4 days. During these outbursts, the gamma-ray flux from the nebula increased by factors of four and six, respectively. The brevity of the flares implies that the gamma rays were emitted via synchrotron radiation from peta-electron-volt (10(15) electron volts) electrons in a region smaller than 1.4 × 10(-2) parsecs. These are the highest-energy particles that can be associated with a discrete astronomical source, and they pose challenges to particle acceleration theory.

[Granulomatous pulmonary involvement preceding diagnosis of Crohn disease: a pediatric case report]. / Atteinte granulomateuse pulmonaire précédant le diagnostic de maladie de Crohn: à propos d'un cas pédiatrique.

Crohn disease (CD) is a chronic bowel disorder that may affect many other organs such as the eyes, hepatobiliary system, skin, and joints. Pulmonary involvement in association with CD is a classic but uncommon manifestation. It can be primitive with granulomas or secondary to treatments. We report on the case of a teenager in whom the onset of CD was dominated by respiratory symptoms. Because of this presentation, we also suspected opportunistic infections such as tuberculosis and other granulomatous pulmonary diseases such as sarcoidosis or hypersensitivity pneumonitis.

Triply differential single ionization of argon: charge effects for positron and electron impact.

Triply differential single ionization of Ar by 200 eV positron and electron impact is measured and calculated. For an unequivocal test of kinematic differences, fully differential ejected electron angular distributions are measured using the same experimental apparatus and conditions for both positron and electron impact. The binary/recoil intensity ratios are shown to significantly differ for the two projectiles. These data are used to test theoretical calculations.