185 research outputs found

    Beyond Depoliticized Citizenship Education. Conceptualizing Political Citizenship Education in Citizenship Education Theory

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    This study aims to contribute to the development of a comprehensive conception of political citizenship education. Through a conceptual review the work of scholars who have written extensively about the dangers of apolitical citizenship education and/or the need for political citizenship education are examined. In particular, it analyzed notions of politics and citizenship and conceptions of depoliticized and political citizenship education from which key characteristics of political citizenship education are derived. The political theories of Rancière, Mouffe and Castoriadis were taken into account, for they have influenced several of the authors’ conceptions of political citizenship education. Analysis of the literature led to the distinction of three subgroups in the data based similar underlying theoretical notions: subjectification, political creation and social justice. Based on the analysis the following key characteristics of political citizenship education have been discerned. Political citizenship education fosters citizens who understand citizenship as a contested concept; are inclined to question relations of power; are sensitive to possibilities for (political) change; can identify with collectives or with issues of a common concern; are capable of engaging in conflict; see themselves as (equal) political subjects; understand that institutions are created by people and can thus be reimagined and recreated; and are oriented toward social justice

    Endoscopic Resection Without Subsequent Ablation Therapy for Early Barrett's Neoplasia:Endoscopic Findings and Long-Term Mortality

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    INTRODUCTION: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status. METHODS: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality. RESULTS: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC. CONCLUSION: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation

    The Development of Metabolomic Sampling Procedures for Pichia pastoris, and Baseline Metabolome Data

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    Metabolic profiling is increasingly being used to investigate a diverse range of biological questions. Due to the rapid turnover of intracellular metabolites it is important to have reliable, reproducible techniques for sampling and sample treatment. Through the use of non-targeted analytical techniques such as NMR and GC-MS we have performed a comprehensive quantitative investigation of sampling techniques for Pichia pastoris. It was clear that quenching metabolism using solutions based on the standard cold methanol protocol caused some metabolite losses from P. pastoris cells. However, these were at a low level, with the NMR results indicating metabolite increases in the quenching solution below 5% of their intracellular level for 75% of metabolites identified; while the GC-MS results suggest a slightly higher level with increases below 15% of their intracellular values. There were subtle differences between the four quenching solutions investigated but broadly, they all gave similar results. Total culture extraction of cells + broth using high cell density cultures typical of P. pastoris fermentations, was an efficient sampling technique for NMR analysis and provided a gold standard of intracellular metabolite levels; however, salts in the media affected the GC-MS analysis. Furthermore, there was no benefit in including an additional washing step in the quenching process, as the results were essentially identical to those obtained just by a single centrifugation step. We have identified the major high-concentration metabolites found in both the extra- and intracellular locations of P. pastoris cultures by NMR spectroscopy and GC-MS. This has provided us with a baseline metabolome for P. pastoris for future studies. The P. pastoris metabolome is significantly different from that of Saccharomyces cerevisiae, with the most notable difference being the production of high concentrations of arabitol by P. pastoris

    Incidental detection of an occult oral malignancy with autofluorescence imaging: a case report

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    BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma. CASE DESCRIPTION: A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during clinical examination. Examination of this lesion using a multispectral oral cancer screening device revealed loss of autofluorescence at 405 nm illumination. An excisional biopsy of this nodule, confirmed the presence of a metastatic squamous cell carcinoma. Four years ago, this patient was diagnosed with metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown primary. She was treated with external beam irradiation and remained disease free until current presentation. CONCLUSION: This case illustrates the important role played by autofluorescence tissue imaging in diagnosing a metastatic palatal tumour that appeared clinically innocuous and otherwise would not have been biopsied

    Application of magnifying narrow-band imaging endoscopy for diagnosis of early gastric cancer and precancerous lesion

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    <p>Abstract</p> <p>Background</p> <p>Gastric carcinoma is the second commonest cause of cancer deaths worldwide. Early detection and diagnosis of gastric cancer in the stomach is important for improving the prognosis of gastric cancer. This retrospective study was designed to investigate the value of magnifying narrow-band imaging (NBI) in the diagnosis of precancerous lesions and early gastric cancer.</p> <p>Methods</p> <p>This study included 122 patients who were diagnosed with early gastric cancer or precancerous gastric lesions by endoscopy. The patients underwent an examination with conventional endoscopy, magnifying NBI, and magnifying chromoendoscopy. Images resolution was evaluated, and the morphology, pit patterns and blood capillary forms of lesions were analyzed. The presence of gastric carcinoma and high grade intraepithelial neoplasia in the biopsy samples was considered as a positive pathological result, which is used to assess accuracy of endoscopic diagnosis.</p> <p>Results</p> <p>For image resolution, magnifying NBI and magnifying chromoendoscopy were significantly superior to magnifying conventional endoscopy in morphology, pit pattern and blood capillary form (P < 0.01), and magnifying NBI was significantly superior to magnifying chromoendoscopy in blood capillary form (P < 0.01). IV, V<sub>1</sub>, and VI type of gastric pit pattern were detected in 14 cases, 43 cases, and 17 cases in patients with high grade intraepithelial neoplasia, respectively. V<sub>1 </sub>and VI type of gastric pit pattern were detected in 9 cases and 39 cases in patients with early gastric cancer, respectively. The presence of irregular minute vessels and variation in the caliber of vessels was found in 109 cases. The accuracy, sensitivity, specificity, false positive rate and false negative rate for diagnosis of early gastric cancer and precancerous gastric lesions were 68.9%, 95.1%, 63.1%, 24.5%, and 32.4% for conventional endoscopy, 93.6%, 92.7%, 94.5%, 5.7%, and 6.9% for magnifying NBI, and 91.3%, 88.6%, 93.2%, 13.2%, and 21.48% for magnifying chromoendoscopy, respectively.</p> <p>Conclusions</p> <p>This study demonstrates that magnifying NBI is superior to conventional endoscopy in the diagnosis of early gastric cancer and precancerous gastric lesions, and can be used for screening early malignancies of the stomach.</p

    Dysplastic Recurrence After Successful Treatment for Early Barrett's Neoplasia:Development and Validation of a Prediction Model

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    Background & Aims: The combination of endoscopic resection and radiofrequency ablation is the treatment of choice for eradication of Barrett's esophagus (BE) with dysplasia and/or early cancer. Currently, there are no evidence-based recommendations on how to survey patients after successful treatment, and most patients undergo frequent follow-up endoscopies. We aimed to develop and externally validate a prediction model for visible dysplastic recurrence, which can be used to personalize surveillance after treatment. Methods: We collected data from the Dutch Barrett Expert Center Registry, a nationwide registry that captures outcomes from all patients with BE undergoing endoscopic treatment in the Netherlands in a centralized care setting. We used predictors related to demographics, severity of reflux, histologic status at baseline, and treatment characteristics. We built a Fine and Gray survival model with least absolute shrinkage and selection operator penalization to predict the incidence of visible dysplastic recurrence after initial successful treatment. The model was validated externally in patients with BE treated in Switzerland and Belgium. Results: A total of 1154 patients with complete BE eradication were included for model building. During a mean endoscopic follow-up of 4 years, 38 patients developed recurrent disease (1.0%/person-year). The following characteristics were independently associated with recurrence (strongest to weakest predictor): a new visible lesion during treatment phase, higher number of endoscopic resection treatments, male sex, increasing BE length, high-grade dysplasia or cancer at baseline, and younger age. External validation showed a C-statistic of 0.91 (95% confidence interval, 0.86–0.94) with good calibration. Conclusions: This is the first externally validated model to predict visible dysplastic recurrence after successful endoscopic eradication treatment of BE with dysplasia or early cancer. On external validation, our model has good discrimination and calibration. This model can help clinicians and patients to determine a personalized follow-up strategy

    Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis.

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    Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n=66) and high-grade dysplasia (HGD; n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies

    Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma:a nationwide analysis

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    Introduction: Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). Aim: assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Patients and methods: Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014–2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). Results: 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89–100%), SFM-b6 was 44% (20–77%), and SFM-b5+6 was 65% (53–90%). All centers met the performance target RAS&gt;85%. Only 9 out of 17 met the performance target SFM-b5+6 &gt; 85%. Conclusion: This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated

    Lymphovascular invasion quantification could improve risk prediction of lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma

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    AIM: To quantify lymphovascular invasion (LVI) and to assess the prognostic value in patients with pT1b esophageal adenocarcinoma. METHODS: In this nationwide, retrospective cohort study, patients were included if they were treated with surgery or endoscopic resection for pT1b esophageal adenocarcinoma. Primary endpoint was the presence of metastases, lymph node metastases, or distant metastases, in surgical resection specimens or during follow‐up. A prediction model to identify risk factors for metastases was developed and internally validated. RESULTS: 248 patients were included. LVI was distributed as follows: no LVI (n = 196; 79.0%), 1 LVI focus (n = 16; 6.5%), 2–3 LVI foci (n = 21; 8.5%) and ≥4 LVI foci (n = 15; 6.0%). Seventy‐eight patients had metastases. The risk of metastases was increased for tumors with 2–3 LVI foci [subdistribution hazard ratio (SHR) 3.39, 95% confidence interval (CI) 2.10–5.47] and ≥4 LVI foci (SHR 3.81, 95% CI 2.37–6.10). The prediction model demonstrated a good discriminative ability (c‐statistic 0.81). CONCLUSION: The risk of metastases is higher when more LVI foci are present. Quantification of LVI could be useful for a more precise risk estimation of metastases. This model needs to be externally validated before implementation into clinical practice
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