Learning to read a second language (L2) can pose a great challenge for children who have already been struggling to read in their first language (L1). Moreover, it is not clear whether, to what... Show moreLearning to read a second language (L2) can pose a great challenge for children who have already been struggling to read in their first language (L1). Moreover, it is not clear whether, to what extent, and under what circumstances L1 reading difficulty increases the risk of L2 reading difficulty. This study investigated Chinese (L1) and English (L2) reading skills in a large representative sample of 1,824 Chinese–English bilingual children in Grades 4 and 5 from both urban and rural schools in Beijing. We examined the prevalence of reading difficulty in Chinese only (poor Chinese readers, PC), English only (poor English readers, PE), and both Chinese and English (poor bilingual readers, PB) and calculated the co-occurrence, that is, the chances of becoming a poor reader in English given that the child was already a poor reader in Chinese. We then conducted a multinomial logistic regression analysis and compared the prevalence of PC, PE, and PB between children in Grade 4 versus Grade 5, in urban versus rural areas, and in boys versus girls. Results showed that compared to girls, boys demonstrated significantly higher risk of PC, PE, and PB. Meanwhile, compared to the 5th graders, the 4th graders demonstrated significantly higher risk of PC and PB. In addition, children enrolled in the urban schools were more likely to become better second language readers, thus leading to a concerning rural–urban gap in the prevalence of L2 reading difficulty. Finally, among these Chinese–English bilingual children, regardless of sex and school location, poor reading skill in Chinese significantly increased the risk of also being a poor English reader, with a considerable and stable co-occurrence of approximately 36%. In sum, this study suggests that despite striking differences between alphabetic and logographic writing systems, L1 reading difficulty still significantly increases the risk of L2 reading difficulty. This indicates the shared meta-linguistic skills in reading different writing systems and the importance of understanding the universality and the interdependent relationship of reading between different writing systems. Furthermore, the male disadvantage (in both L1 and L2) and the urban–rural gap (in L2) found in the prevalence of reading difficulty calls for special attention to disadvantaged populations in educational practice. Show less
Bayer, S.; Zhai, Z.W.; Strumia, M.; Tong, X.G.; Gao, Y.; Staring, M.; ... ; Ravikumar, N. 2019
Purpose Morphological changes to anatomy resulting from invasive surgical procedures or pathology, typically alter the surrounding vasculature. This makes it useful as a descriptor for feature... Show morePurpose Morphological changes to anatomy resulting from invasive surgical procedures or pathology, typically alter the surrounding vasculature. This makes it useful as a descriptor for feature-driven image registration in various clinical applications. However, registration of vasculature remains challenging, as vessels often differ in size and shape, and may even miss branches, due to surgical interventions or pathological changes. Furthermore, existing vessel registration methods are typically designed for a specific application. To address this limitation, we propose a generic vessel registration approach useful for a variety of clinical applications, involving different anatomical regions. Methods A probabilistic registration framework based on a hybrid mixture model, with a refinement mechanism to identify missing branches (denoted as HdMM+) during vasculature matching, is introduced. Vascular structures are represented as 6-dimensional hybrid point sets comprising spatial positions and centerline orientations, using Student's t-distributions to model the former and Watson distributions for the latter. Results The proposed framework is evaluated for intraoperative brain shift compensation, and monitoring changes in pulmonary vasculature resulting from chronic lung disease. Registration accuracy is validated using both synthetic and patient data. Our results demonstrate, HdMM+ is able to reduce more than 85% of the initial error for both applications, and outperforms the state-of-the-art point-based registration methods such as coherent point drift and Student's t-distribution mixture model, in terms of mean surface distance, modified Hausdorff distance, Dice and Jaccard scores. Conclusion The proposed registration framework models complex vascular structures using a hybrid representation of vessel centerlines, and accommodates intricate variations in vascular morphology. Furthermore, it is generic and flexible in its design, enabling its use in a variety of clinical applications. Show less
Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form N-methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number... Show moreNicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form N-methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number of cancers and metabolic disorders, suggesting a role for NNMT as a potential therapeutic target. By structural modification of a lead NNMT inhibitor previously developed in our group, we prepared a diverse library of inhibitors to probe the different regions of the enzyme’s active site. This investigation revealed that incorporation of a naphthalene moiety, intended to bind the hydrophobic nicotinamide binding pocket via π–π stacking interactions, significantly increases the activity of bisubstrate-like NNMT inhibitors (half-maximal inhibitory concentration 1.41 μM). These findings are further supported by isothermal titration calorimetry binding assays as well as modeling studies. The most active NNMT inhibitor identified in the present study demonstrated a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line. Show less
Yang, C.; Gavazzi, R.; Beelen, A.; Cox, P.; Omont, A.; Lehnert, M.D.; ... ; Werf, P.P. van der 2019
Background: The potential survival benefits of adding radiotherapy to systemic therapy for esophageal cancer patients with oligometastases are unknown.Methods: In this retrospective analysis,... Show moreBackground: The potential survival benefits of adding radiotherapy to systemic therapy for esophageal cancer patients with oligometastases are unknown.Methods: In this retrospective analysis, patients with stage IV esophageal cancer (according to the American Joint Committee on Cancer Seventh edition staging system) with <= 3 metastases who underwent chemotherapy with cisplatin/paclitaxel between 2012 and 2015 were identified. Patients received chemotherapy (CT) alone vs. concurrent chemoradiotherapy (CCRT) to all metastases.Results: Of 461 patients, 97% had squamous cell cancer. One hundred and ninety-six patients (42.5%) received CCRT and 265 (57.5%) underwent CT alone. At week 8, there were 3 (1.5%) complete responses (CR) and 95 (48.5%) partial responses (PR) in the CCRT group, compared to 3 (1.1%) CR and 102 (38.5%) PR in the CT alone group. The overall rate of improvement in dysphagia score was noted in 78.5% of patients in the CCRT group versus 61.5% in the CT alone group (P=0.014). A statistically significant difference was demonstrated in disease control rate between the two groups (81.6% vs. 64.5%, P<0.001). Patients who underwent CCRT had superior median PFS and a trend toward longer median OS compared to those receiving CT alone (8.7 vs. 7.3 months, P=0.002 and 16.8 vs. 14.8 months, P=0.056, respectively). The median OS was 19.3 months in patients who achieved CR/PR, compared to 14.9 months and 9.6 months for patients who had stable disease and progressive disease, respectively (P<0.001).Conclusions: Compared to chemotherapy alone, chemoradiation to all sites in patients with esophageal cancer with <= 3 metastases may lead to a modest increase in PFS and a trend toward longer OS. Further investigation of optimal integration of radiotherapy and chemotherapy in these patients is warranted. Show less
