243 research outputs found
Epstein-Barr virus encoded BARF1 protein: immunopathogenic role, transcriptional regulation and diagnostic use in nasopharyngeal carcinoma
No full textMiddeldorp, J.M. [Promotor]Greijer, A.E. [Copromotor
Short-term effect of different teaching methods on nasopharyngeal carcinoma for general practitioners in Jakarta, Indonesia
No full textIn Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period.Maarten A. Wildeman, Renske Fles, Marlinda Adham, Ika D. Mayangsari, Ilse Luirink, Mara Sandberg, Andrew D. Vincent, Faiziah Fardizza, Zanil Musa, Armiyanto, Jaap M. Middeldorp, Geerten Gerritsen, Ronny Suwanto, I. Bing Ta
Erratum: Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function (Proceedings of the National Academy of Sciences of the United States of America (2019) 116 (26614-26624) DOI: 10.1073/pnas.1915372116)
No full textCorrection for “Reactivation of Epstein–Barr virus by a dualresponsive fluorescent EBNA1-targeting agent with Zn2+- chelating function,” by Lijun Jiang, Hong Lok Lung, Tao Huang, Rongfeng Lan, Shuai Zha, Lai Sheung Chan, Waygen Thor, Tik-Hung Tsoi, Ho-Fai Chau, Cecilia Boreström, Steven L. Cobb, Sai Wah Tsao, Zhao-Xiang Bian, Ga-Lai Law, Wing-Tak Wong, William Chi-Shing Tai, Wai Yin Chau, Yujun Du, Lucas Hao Xi Tang, Alan Kwok Shing Chiang, Jaap M. Middeldorp, Kwok-Wai Lo, Nai Ki Mak, Nicholas J. Long, and Ka-Leung Wong, which was first published December 10, 2019; 10.1073/pnas.1915372116 (Proc. Natl. Acad. Sci. U.S.A. 116, 26614–26624). The authors note that Fig. 6 appeared incorrectly. Part of panel D of the published figure was inadvertently omitted. The corrected figure and its legend appear below. (Figure Presented)
Can an online clinical data management service help in improving data collection and data quality in a developing country setting?
No full textBackground: Data collection by Electronic Medical Record (EMR) systems have been proven to be helpful in data collection for scientific research and in improving healthcare. For a multi-centre trial in Indonesia and the Netherlands a web based system was selected to enable all participating centres to easily access data. This study assesses whether the introduction of a Clinical Trial Data Management service (CTDMS) composed of electronic Case Report Forms (eCRF) can result in effective data collection and treatment monitoring. Methods: Data items entered were checked for inconsistencies automatically when submitted online. The data were divided into primary and secondary data items. We analysed both the total number of errors and the change in error rate, for both Primary and Secondary items, over the first five month of the trial. Results: In the first five months 51 patients were entered. The Primary data error rate was 1.6%, whilst that for Secondary data was 2.7% against acceptable error rates for analysis of 1% and 2.5% respectively. Conclusion: The presented analysis shows that after five months since the introduction of the CTDMS the Primary and Secondary data error rates reflect acceptable levels of data quality. Furthermore, these error rates were decreasing over time. The digital nature of the CTDMS, as well as the online availability of that data, gives fast and easy insight in adherence to treatment protocols. As such, the CTDMS can serve as a tool to train and educate medical doctors and can improve treatment protocols.Maarten A Wildeman, Jeroen Zandbergen, Andrew Vincent, Camelia Herdini, Jaap M Middeldorp, Renske Fles, Otilia Dalesio, Emile van der Donk, I Bing Ta
Molecular diagnosis of viral infections in renal transplant recipients
No full textPURPOSE OF REVIEW: To discuss biological and methodological aspects of virus infection monitoring in the renal transplant setting. RECENT FINDINGS: New insights on the molecular pathogenesis of acute and persistent virus infections and rapid developments in real-time monitoring techniques are changing the current diagnostic routine. Accurate risk-assessment prior to transplantation and quantitative monitoring of parameters that reflect virus activity in the post-transplant period, including genome load fluctuations and aberrant viral mRNA or protein expression, provide early signs of undesired viral behaviour and allow pre-emptive therapeutic intervention. As opposed to prophylactic administration of antiviral drugs, a pre-emptive approach is more selective and will allow for antiviral immune responses to build, which may have a long-term beneficial effect. In addition, these virus-monitoring techniques allow for on-line assessment of therapeutic efficacy and rapid identification of emerging resistant strains. The combination of virus-monitoring techniques with rapid assessment of host immune responses using FACS and ELISPOT techniques, will improve overall patient management and long-term survival. SUMMARY: Viral infections continue to be a significant complication in the transplant setting. Diagnostic monitoring allows timely and accurate therapeutic intervention. Knowledge of pathogenic mechanisms leading to disease is important for clinical decision making as well as for the selection of appropriate molecular parameters discriminating normal and disease-related activity of human pathogenic viruses. The increasing availability of effective antiviral drugs permits pre-emptive intervention that strongly depends on accurate viral monitoring procedures
Primary Treatment Results of Nasopharyngeal Carcinoma (NPC) in Yogyakarta, Indonesia
No full textINTRODUCTION Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia. METHODS All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment. RESULTS In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18–35) from day of diagnosis. CONCLUSION The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.Maarten A. Wildeman, Renske Fles, Camelia Herdini, Rai S. Indrasari, Andrew D. Vincent, Maesadji Tjokronagoro, Sharon Stoker, Johan Kurnianda, Baris Karakullukcu, Kartika W. Taroeno- Hariadi, Olga Hamming-Vrieze, Jaap M. Middeldorp, Bambang Hariwiyanto, Sofia M. Haryana, I. Bing Ta
The Role of EBV Markers in Diagnosis, Treatment and Monitoring of Nasopharyngeal Carcinoma in Jakarta, Indonesia
No full textpromotiedatum: 25-9-2014 � prom-id: 973
The Effective Notch Stress Approach for a Tubular Joint
No full textOffshore wind energy production is increasing rapidly and optimising the design of support structures has the potential to significantly reduce steel and costs. Jacket structures are commonly selected for deeper waters, and the design of these structures is primarily influenced by the fatigue performance of the tubular joints. The fatigue resistance of these joints can typically be evaluated using different stress assessment methods, each associated with a corresponding S-N curve. While the Hot Spot Stress (HSS) approach is commonly used for design purposes, the Effective Notch Stress (ENS) approach offers higher accuracy by taking into account the stress concentration originating from the weld profile. Consequently, the ENS approach has the potential to provide less conservative fatigue life estimations, leading to the reduction of steel and costs. However, the application to and research of the ENS approach for tubular joints is limited. Therefore, the objective of this thesis is to investigate the application of the ENS approach on a tubular joint. The research was divided into three parts, including an investigation on the required FE mesh, a study on sub-modeling of the ENS approach and a comparative analysis on the fatigue life predictions between the HSS and ENS approaches.The FE mesh required for the ENS approach was evaluated on a cruciform joint according to the DNV-RP-C203 validation methodology and the Stress Concentration Factors (SCFs) values obtained for different mesh configurations were compared. Two mesh variants were developed, and different element sizes in the notch were evaluated. The results show that with a maximum element size in the notch equal to 0.39 mm, according to DNV, unacceptable SCF errors are obtained of -4% and 4%. Furthermore, with a maximum notch element size of 0.25 mm, according to IIW, SCF errors of -0.3% and -2.2% were obtained, indicating that accurate results can be obtained but are not guaranteed. Additionally, the accuracy of the mesh was found to be primarily influenced by the number of nodes surrounding the notch, rather than the size of the elements in the notch.The accuracy of sub-modeling for the ENS approach on a tubular T-joint was evaluated by varying global modeling choices and sub-model sizes. The accuracy was measured by comparing sub-modeling stress results against those from a global T-joint FE model with the ENS approach applied. The results show that a global model composed of 3D elements with a weld profile that corresponds to the sub-model is recommended. Simplifying the global model by excluding the weld profile or using 2D elements has been found to provide inconsistent and inaccurate results. Moreover, a sub-model of the weld area with a size as small as 1.67 degrees of the brace radial angle has been found to provide consistent results. Thereby, sub-modeling reduces the required mesh size by a factor of 15, compared to the global modeling approach. Additionally, a rather surprising maximum principal stress error of approximately -6% was observed as a result of sub-modeling for all varied load types and sub-model sizes.A comparative study between the HSS and the ENS approach was conducted for the computed fatigues of a tubular T-joint. Various FE models were composed for the T-joint subjected to different load cases, and equivalent SCFs were computed by introducing a correction factor based on the S-N curves of both approaches. The results show that the ENS approach provides a lower computed fatigue life over the HSS approach when applied to a tubular joint. This discrepancy is attributed to the FAT225 S-N curve, used for the ENS approach, which is not tailored for tubular joints but for welded straight plates. For the HSS approach, the choice of element type (2D vs 3D) and the inclusion of a weld profile have a significant effect on the stress distribution and the resulting fatigue life prediction. It was found that a model consisting of 3D elements with the inclusion of a weld profile yields the longest computed fatigue life for a tubular joint.To conclude, the application of the ENS approach was investigated for a tubular joint, by evaluating the mesh sensitivity, examining the accuracy of sub-modeling and comparing the computed fatigue lives with those from the HSS approach. Further research is recommended to improve the computational efficiency of the ENS mesh and to achieve a deeper understanding of the -6% error found by sub-modeling. Additionally, the development of an S-N curve tailored for tubular joints is suggested to improve the accuracy of the ENS approach for this type of joint.Civil Engineering | Structural Engineerin
Detecting clonality in contralateral breast cancers
No full textWhen a second tumor arises in the contralateral breast in a patient with a previous or synchronous breast cancer, it is of clinical importance to determine if this tumor is a new unrelated tumor or a metastasis, i.e. clone, of the primary tumor. A new, unrelated tumor may be treated similarly as the first one since treatment was successful, while a distant metastasis demands a change of therapy and has a more adverse prognosis. In clinic, a second tumor is generally regarded as a new primary. If there is clinical suspicion that the second tumor may be a metastasis, clinico-pathological characteristics of the two tumors are used assess the clonality status. Clinico-pathological characteristics, however, are not reliable predictors to determine if a second tumor is a metastasis. Recent studies have investigated tumor clonality using techniques from molecular genetics. These models appear to perform well, but have several drawbacks.In this thesis a more advanced classification model is being developed that can detect tumor clonality based on SNP array data. For this, two segmentation algorithms, ASCAT and OncoSNP, and two comparison methods, Log LR and adapted SI, have been incorporated. For each tumor, the segmentation algorithms construct a copy number profile based on the SNP array data. Given the copy number profiles, the comparison methods compute a p-value which reflects the probability that a pair is of clonal origin. Both comparison methods are permutation methods which test the null hypothesis of independence against the alternative hypothesis assuming clonality. The proposed model consists of a decision tree which assigns each pair to one of six categories depending on the significance of the four resulting p-values.The model has been tested on 23 fresh frozen pairs by means of expert judgment. The results were promising: the four pairs which were unanimously labeled as clonal by the experts were also regarded as such by the model. No independent pairs were assigned as clonal by the model. Moreover, the decision tree showed to have a higher sensitivity than the clinical assessments as the latter only managed to detect two out of four clonal pairs. A discordance between the clinico-pathological judgments and decision tree results was found for three out of 18 pairs for which both assessments were available.The model appears to be suitable in practice, but is not yet applicable as a stand-alone model. There were two ambiguous pairs which were labeled as independent by the model but for which the experts had varying opinions about the clonality status. Until the ambiguous pairs can be reliably categorized, it is advised to take into account both the model results and clinical assessments when determining tumor clonality. Finally, the performance of the model remains to be tested on FFPE pairs.Applied Mathematic
- …
