Outcome of radiotherapy in T1 glottic carcinoma: A population-based study

We evaluated the radiation outcome and prognostic factors in a population-based study of early (T1N0M0) glottic carcinoma. Survival parameters and prognostic factors were evaluated by uni- and multivariate analysis in 316 consecutive irradiated patients with T1 glottic carcinoma in the Comprehensive Cancer Center West region of the western Netherlands. Median follow-up was 70 months (range 1-190 months). Five and ten-year local control was 86 and 84%. Disease specific survival was 97% at 5 and 10 years. In multivariate analysis, pre-existent laryngeal hypertrophic laryngitis was the only predictive factor for local control (relative risk = 3.0, P = 0.02). Comorbidity was prognostic for overall survival. No factor was predictive for disease specific survival. Pre-existent laryngeal hypertrophic laryngitis is a new risk factor associated with reduced local control in T1 glottic carcinoma treated with radiotherapy

The general framework for few-shot learning by kernel HyperNetworks

Few-shot models aim at making predictions using a minimal number of labeled examples from a given task. The main challenge in this area is the one-shot setting, where only one element represents each class. We propose the general framework for few-shot learning via kernel HyperNetworks—the fusion of kernels and hypernetwork paradigm. Firstly, we introduce the classical realization of this framework, dubbed HyperShot. Compared to reference approaches that apply a gradient-based adjustment of the parameters, our models aim to switch the classification module parameters depending on the task’s embedding. In practice, we utilize a hypernetwork, which takes the aggregated information from support data and returns the classifier’s parameters handcrafted for the considered problem. Moreover, we introduce the kernel-based representation of the support examples delivered to hypernetwork to create the parameters of the classification module. Consequently, we rely on relations between the support examples’ embeddings instead of the backbone models’ direct feature values. Thanks to this approach, our model can adapt to highly different tasks. While such a method obtains very good results, it is limited by typical problems such as poorly quantified uncertainty due to limited data size. We further show that incorporating Bayesian neural networks into our general framework, an approach we call BayesHyperShot, solves this issue

Synthesis of 2′-Fluoro RNA by Syn5 RNA polymerase

The substitution of 2′-fluoro for 2′-hydroxyl moieties in RNA substantially improves the stability of RNA. RNA stability is a major issue in RNA research and applications involving RNA. We report that the RNA polymerase from the marine cyanophage Syn5 has an intrinsic low discrimination against the incorporation of 2′-fluoro dNMPs during transcription elongation. The presence of both magnesium and manganese ions at high concentrations further reduce this discrimination without decreasing the efficiency of incorporation. We have constructed a Syn5 RNA polymerase in which tyrosine 564 is replaced with phenylalanine (Y564F) that further decreases the discrimination against 2′-fluoro-dNTPs during RNA synthesis. Sequence elements in DNA templates that affect the yield of RNA and incorporation of 2′-fluoro-dNMPs by Syn5 RNA polymerase have been identified

The prognostic value of contrast echocardiography, electrocardiographic and angiographic perfusion indices for prediction of left ventricular function recovery in patients with acute myocardial infarction treated by percutaneous coronary intervention

Background: Fast and effective culprit artery patency restoration is important in acute myocardial infarction (MI) but does not ensure that tissue perfusion related to a better prognosis in the long-term follow-up is achieved. In this study we compared the prognostic value of myocardial perfusion contrast echocardiography with other well-known electrocardiographic and angiographic indices of preserved tissue perfusion. Material and methods: We studied 114 consecutive patients, of whom 85 were male, aged 57.9 &#177; 11 years, within 12 hours of the onset of symptoms of their first anterior myocardial infarction. These were treated with primary PCI, after which PCI myocardial blush grading was assessed (MBG 0-1 no perfusion, 2-3 normal perfusion). One hour after PCI a reduction of > 50% in the sum of ST-segment elevation (&#931;ST 50%) was assessed as an indicator of perfusion restoration. During the first 24 hours continuous ECG monitoring recorded reperfusion arrhythmias (RA) and the time required for ST-segment reduction to exceed 50% in the single lead with the highest ST elevation (&#916;t ST 50%). On the next day of MI, after LVEF evaluation, real-time myocardial contrast echocardiography (RT-MCE) was performed to assess perfusion in dysfunctional segments. The reperfusion index as an average of the dysfunctional segment perfusion score was determined. Regional and global LV function was assessed again one month after MI. An LVEF increase of over 5% divided the patients into two groups: group A with LVEF improvement (72 pts) and group B without LVEF improvement (42 pts). Results: In group A baseline LVEF was 41.9 &#177; 7.1% and in group B it was 38.9 &#177; 7.4% (p = NS). The reperfusion indices were 1.59 and 0.78 (p < 0.001) respectively. MBG 2-3 occurred more often in group A (64%) than in group B (34%) p < 0.001. &#931; ST50% and &#916;t ST 50%, after determination of the cut point on the ROC curve (61 min), occurred in 47 and 48 patients in group A and 17 and 16 patients in group B respectively. The accuracy of the tests under discussion for LVEF prognosis was 76.3%, 64%, 63.2% and 64.9% for RT-MCE, MBG, SST50% and &#916;t ST 50% respectively. Conclusions: Myocardial perfusion echocardiography had a high prognostic value for the prediction of LV global function improvement. It turned out to be the best predictor among the other angiographic, echocardiographic and electrocardiographic markers

A new method of volume determination in three-dimensional ultrasonography

Background: The aim of this work was to develop a method of volume determination utilizing the grey scale histogram of three-dimensional (3D) ultrasonic (US) image. Volumes are calculated as the product of single voxel volume and the area of histogram peak representing investigated object. The proposed solution performance was compared with two other methods. First utilizes two-dimensional crosssection areas on subsequent image layers while the second allows the volume determination on the basis of one-dimensional measurements. Material/Methods: The 3D US phantoms images were used to test the procedure. The usefulness of the method was also demonstrated on several clinical examples. The ultrasonic 3D images were collected, their histograms calculated and fitted with model curves allowing the volume calculations. The accuracy and precision was assessed and t-test was used for evaluating performance of all considered methods. Results: The accuracy (understood as the difference between real and measured volume) achieved in the proposed solution (3.6%) was the highest comparing to alternative methods (5.2% and 8.4%). Also the p-value (two-tailed t-test) was better in the case of the presented method. The performance increase was due to the elimination of subjective delineation of measured regions of interest. Conclusions: The presented procedure can be successfully used for volume assessment concerning its simplicity, accuracy and time consumption. It should be emphasized that the new method does not require image segmentation, unlike other methods in use. The procedure was tested with 3D US imaging but can be used successfully with any 3D imaging modality

Economic evaluation of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis: a cost-minimization analysis

textabstractPurpose: To assess the cost-effectiveness of Multiplex Ligation-dependent Probe Amplification (MLPA, P095 kit) compared to karyotyping. Methods: A cost-minimization analysis alongside a nationwide prospective clinical study of 4,585 women undergoing amniocentesis on behalf of their age (≥36 years), an increased risk following first trimester prenatal screening or parental anxiety. Results: Diagnostic accuracy of MLPA (P095 kit) was comparable to karyotyping (1.0 95% CI 0.999-1.0). Health-related quality of life did not differ between the strategies (summary physical health: mean difference 0.31, p = 0.82; summary mental health: mean difference 1.91, p = 0.22). Short-term costs were lower for MLPA: mean difference €315.68 (bootstrap 95% CI €315.63-315.74; -44.4%). The long-term costs were slightly higher for MLPA: mean difference €76.42 (bootstrap 95% CI €71.32-81.52; +8.6%). Total costs were on average €240.13 (bootstrap 95% CI €235.02-245.23; -14.9%) lower in favor of MLPA. Cost differences were sensitive to proportion of terminated pregnancies, sample throughput, individual choice and performance of tests in one laboratory, but not to failure rate or the exclusion of polluted samples. Conclusion: From an economic perspective, MLPA is the preferred prenatal diagnostic strategy in women who undergo amniocentesis on behalf of their age, following prenatal screening or parental anxiety

Porównanie wartości prognostycznej echokardiografii kontrastowej z elektrokardiograficznymi i angiograficznymi wskaźnikami oceny perfuzji w przewidywaniu poprawy funkcji skurczowej lewej komory u pacjentów z ostrym zawałem serca leczonych pierwotną interwencją wieńcową

Wstęp: Szybkie i skuteczne przywrócenie drożności tętnicy dozawałowej, a przede wszystkim trwałe przywrócenie perfuzji tkankowej, wiążą się z poprawą rokowania i lepszą funkcją skurczową lewej komory w obserwacji odległej w porównaniu z osobami z zaburzoną perfuzją. Celem przedstawionego badania jest porównanie wartości prognostycznej perfuzyjnej echokardiografii kontrastowej z innymi, ogólnie uznanymi elektrokardiograficznymi i angiograficznymi wskaźnikami oceny perfuzji tkankowej. Materiał i metody: Badaniem objęto kolejnych 114 pacjentów (85 M; 57,9 &plusmn; 11 lat) z pierwszym zawałem ściany przedniej (12 godzin od początku) leczonych PCI. Po udanej PCI dokonywano angiograficznej oceny perfuzji (MBG 0-1 brak perfuzji, 2-3 zachowana perfuzja), a następnie po 60 min wykonywano EKG w celu oceny stopnia redukcji sumy uniesień odcinka ST. Zmniejszenie sumy uniesień powyżej 50% (&#931;ST50%) było wskaźnikiem powrotu perfuzji. Przez pierwsze 24 godziny monitorowano 12-odprowadzeniowe EKG w celu rejestracji arytmii w czasie reperfuzji (RA) i czasu zmniejszenia uniesienia ST o ponad 50% w pojedynczym odprowadzeniu z najwyższym uniesieniem ST (&#916;tST50%). W 2. dobie zawału po oznaczeniu frakcji wyrzutowej lewej komory (LVEF) oceniano perfuzję w segmentach dysfunkcyjnych, posługując się echokardiografią kontrastową (RT-MCE), a wskaźnik perfuzyjny (RPSI) stanowił średnią z wyników perfuzji segmentów dysfunkcyjnych. Regionalną i globalną kurczliwość LV oceniano ponownie po miesiącu, a na podstawie wzrostu LVEF o ponad 5% podzielono pacjentów na grupy A (z poprawą funkcji skurczowej; 72 osoby) i B (bez poprawy funkcji skurczowej; 42 osoby).Wyniki: W grupie A LVEF wynosiła 41,9% &plusmn; 7,1%, a w grupie B &#8212; 38,9 &plusmn; 7,4% (p = NS), natomiast wskaźnik RPSI odpowiednio: 1,59 i 0,78 (p < 0,001). Prawidłowa perfuzja oceniana angiograficznie (MBG 2-3) występowała częściej w grupie A (64%) w stosunku do grupy B (34%; p < 0,001). Wśród badanych pacjentów &#931;ST50% i &#916;tST50% po wyznaczeniu punktu odcięcia z krzywej ROC (61 min) wystąpiły u 47 i 48 pacjentów z grupy A oraz 17 i 16 z grupy B. Dokładność omawianych testów dla prognozowania poprawy funkcji LV wynosiła odpowiednio: 76,3%, 64%, 63,2% i 64,9% dla RT-MCE, MBG, &#931;ST50% i &#916;tST50%. Wnioski: W badaniu wykazano wysoką wartość prognostyczną echokardiografii perfuzyjnej w przewidywaniu poprawy globalnej funkcji skurczowej lewej komory, która okazała się najlepszym predykatorem wśród pozostałych wskaźników angiograficznych i elektrokardiograficznych

Effect of maternal administration of betamethasone on peripheral arterial development in fetal rabbit lungs

Objectives: Glucocorticoids promote lung maturation and reduce the incidence of respiratory distress syndrome in premature newborns. We hypothesized that betamethasone (BM), which is known to induce thinning of the alveolar walls, would also thin the arterial media and adventitia of intra-parenchymatic vessels in developing rabbit lungs. Study Design: 112 fetuses from 21 time-mated, pregnant, giant white rabbits received maternal injections of BM at either 0.05 or 0.1 mg/kg/day on days 25-26 of gestational age. Controls received either saline (10 does, 56 fetuses) or no injection (10 does, 59 fetuses). Fetuses were harvested from day 27 onwards until term (day 31). 44 additional fetuses (8 does) were harvested between days 23 and 26. Endpoints were wet lung-to-body weight ratio, vascular morphometric indices and immunohistochemistry staining for α-smooth muscle actin, Flk-1, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). ANOVA (Tukey's test) and independent t test (p < 0.05) were used for comparison between BM and saline groups. Results: Maternal BM injected on days 25-26 to pregnant rabbits induced a significant decrease in fetal body and lung weight and the lung-to-body weight ratio in the preterm pups shortly after injection. BM led to a dose-dependent thinning of the arterial media and adventitia (pulmonary arteries with an external diameter (ED) of <100 μm), to an increase in the percentage of non-muscularized peripheral vessels (ED <60 μm), in eNOS and VEGF immunoreactivity of the endothelial and smooth muscle cells in the pulmonary vessels and to an increase in Flk-1-positive pulmonary epithelial cell density. Conclusions: Maternal administration of BM caused thinning of the arterial wall of pulmonary vessels (ED <100 μm) and a decrease in muscularization in peripheral vessels (ED <60 μm). This coincided with increased expression of Flk-1 in the endothelium and smooth muscle cells of the pulmonary arteries. All the effects studied were dose-dependent. Copyrigh

A GMRT multifrequency radio study of the isothermal core of the poor galaxy cluster AWM 4

We present a detailed radio morphological study and spectral analysis of the wide-angle-tail radio source 4C +24.36 associated with the dominant galaxy in the relaxed galaxy cluster AWM 4. Our study is based on new high sensitivity GMRT observations at 235 MHz, 327 MHz and 610 MHz, and on literature and archival data at other frequencies. We find that the source major axis is likely oriented at a small angle with respect to the plane of the sky. The wide-angle-tail morphology can be reasonably explained by adopting a simple hydrodynamical model in which both ram pressure (driven by the motion of the host galaxy) and buoyancy forces contribute to bend the radio structure. The spectral index progressively steepens along the source major axis from $\alpha \sim$0.3 in the region close to the radio nucleus to beyond 1.5 in the lobes. The results of the analysis of the spectral index image allow us to derive an estimate of the radiative age of the source of $\sim$ 160 Myr. The cluster X-ray emitting gas has a relaxed morphology and short cooling time, but its temperature profile is isothermal out to at least 160 kpc from the centre. Therefore we seek evidence of energy ejection from the central AGN to prevent catastrophic cooling. We find that the energy injected by 4C +24.36 in the form of synchrotron luminosity during its lifetime is far less than the energy required to maintain the high gas temperature in the core. We also find that it is not possible for the central source to eject the requisite energy in the intracluster gas in terms of the enthalpy of buoyant bubbles of relativistic fluid, without creating discernible large cavities in the existing X-ray XMM-Newton observations.Comment: 15 pages, 12 figures, accepted for publication in Ap

Global Molecular Epidemiology of Respiratory Syncytial Virus from the 2017-2018 INFORM-RSV Study

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among infants and young children, resulting in annual epidemics worldwide. INFORM-RSV is a multiyear clinical study designed to describe the global molecular epidemiology of RSV in children under 5 years of age by monitoring temporal and geographical evolution of current circulating RSV strains, F protein antigenic sites, and their relationships with clinical features of RSV disease. During the pilot season (2017-2018), 410 RSV G-F gene sequences were obtained from 476 RSV-positive nasal samples collected from 8 countries (United Kingdom, Spain, The Netherlands, Finland, Japan, Brazil, South Africa, and Australia). RSV B (all BA9 genotype) predominated over RSV A (all ON1 genotype) globally (69.0% versus 31.0%) and in all countries except South Africa. Geographic clustering patterns highlighted wide transmission and continued evolution with viral spread. Most RSV strains were from infants of 24 h (70.5%), with no differences in subtype distribution. Compared to 2013 reference sequences, variations at F protein antigenic sites were observed for both RSV A and B strains, with high-frequency polymorphisms at antigenic site Ø (I206M/Q209R) and site V (L172Q/S173L/K191R) in RSV B strains. The INFORM-RSV 2017-2018 pilot season establishes an important molecular baseline of RSV strain distribution and sequence variability with which to track the emergence of new strains and provide an early warning system of neutralization escape variants that may impact transmission or the effectiveness of vaccines and MAbs under development