Musculoskeletal pain in 6-year-old children: the Generation R Study

Musculoskeletal (MSK) pain is frequently reported among adolescents and children and is a common reason for consultation in primary care. Our aim is to examine its prevalence in 6-year-old children in a general population and to assess associations with physical and psychosocial factors. Data from the Generation R Study, a population-based cohort, was used. Prevalence and characteristics of MSK pain were assessed with parent-reported questionnaires at 6 years of age (N = 6200). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain, and behavioral problems were extracted from questionnaires. The body mass index SD score was calculated from objectively measured weight and height. A 3-month prevalence of 10.0% was found for MSK pain in children, of which one-third was chronic, and 44.6% experienced together with pain at other sites. Univariate analyses showed that boys and children with lower socioeconomic status reported MSK pain more frequently compared to other pain and no pain. Although no associations were found between MSK pain and children's body mass index and physical activity level, children with MSK pain were more likely to watch television ≥2 hours/day. Multivariable analysis showed significant associations for MSK pain at 3 years of age (odds ratio 5.10, 95% confidence interval 3.25-7.98) and behavioral problems (odds ratio 2.10, 95% confidence interval 1.19-3.72) with the presence of MSK pain. So, MSK pain is already common in young children and is often chronic or recurrent. Previous reported MSK pain and behavioral

Nonmalignant portal vein thrombi in patients with cirrhosis consist of intimal fibrosis with or without a fibrin-rich thrombus

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown, and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight into the structure and composition of portal vein thrombi may assist in developing strategies for the prevention and treatment of PVT. APPROACH AND RESULTS: Sixteen prospectively and 63 retrospectively collected nonmalignant portal vein thrombi from patients with cirrhosis who underwent liver transplantation were included. Histology, immunohistochemistry, and scanning electron microscopy were used to assess structure and composition of the thrombi. Most recent CT scans were reanalyzed for thrombus characteristics. Clinical characteristics were related to histological and radiological findings. All samples showed a thickened, fibrotic tunica intima. Fibrin-rich thrombi were present on top of the fibrotic intima in 9/16 prospective cases and in 21/63 retrospective cases. A minority of the fibrotic areas stained focally positive for fibrin/fibrinogen (16% of cases), von Willebrand factor (VWF; 10%), and CD61 (platelets, 21%), while most of the fibrin-rich areas stained positive for those markers (fibrin/fibrinogen, 100%; VWF, 77%; CD61, 100%). No associations were found between clinical characteristics including estimated thrombus age and use of anticoagulants and presence of fibrin-rich thrombi. CONCLUSION: We demonstrate that PVT in patients with cirrhosis consists of intimal fibrosis with an additional fibrin-rich thrombus in only one-third of cases. We hypothesize that our observations may explain why not all portal vein thrombi in patients with cirrhosis recanalize by anticoagulant therapy

Exploring data provenance in handwritten text recognition infrastructure:Sharing and reusing ground truth data, referencing models, and acknowledging contributions. Starting the conversation on how we could get it done

This paper discusses best practices for sharing and reusing Ground Truth in Handwritten Text Recognition infrastructures, and ways to reference and acknowledge contributions to the creation and enrichment of data within these Machine Learning systems. We discuss how one can publish Ground Truth data in a repository and, subsequently, inform others. Furthermore, we suggest appropriate citation methods for HTR data, models, and contributions made by volunteers. Moreover, when using digitised sources (digital facsimiles), it becomes increasingly important to distinguish between the physical object and the digital collection. These topics all relate to the proper acknowledgement of labour put into digitising, transcribing, and sharing Ground Truth HTR data. This also points to broader issues surrounding the use of Machine Learning in archival and library contexts, and how the community should begin toacknowledge and record both contributions and data provenance

Exploring Data Provenance in Handwritten Text Recognition Infrastructure: Sharing and Reusing Ground Truth Data, Referencing Models, and Acknowledging Contributions. Starting the Conversation on How We Could Get It Done

This paper discusses best practices for sharing and reusing Ground Truth in Handwritten Text Recognition infrastructures, as well as ways to reference and acknowledge contributions to the creation and enrichment of data within these systems. We discuss how one can place Ground Truth data in a repository and, subsequently, inform others through HTR-United. Furthermore, we want to suggest appropriate citation methods for ATR data, models, and contributions made by volunteers. Moreover, when using digitised sources (digital facsimiles), it becomes increasingly important to distinguish between the physical object and the digital collection. These topics all relate to the proper acknowledgement of labour put into digitising, transcribing, and sharing Ground Truth HTR data. This also points to broader issues surrounding the use of machine learning in archival and library contexts, and how the community should begin to acknowledge and record both contributions and data provenance

Cancer cell adaptation to chemotherapy

BACKGROUND: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. METHODS: Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. RESULTS: In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. CONCLUSION: This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy