MiRNA expression patterns predict survival in glioblastoma

<p>Abstract</p> <p>Background</p> <p>In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed.</p> <p>Methods</p> <p>35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom^®Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed.</p> <p>Results</p> <p>It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status.</p> <p>Conclusions</p> <p>At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.</p

New constraints on micro-seismicity and stress state in the western part of the North Anatolian Fault Zone : Observations from a dense seismic array

Major funding was provided by the UK Natural Environment Research Council (NERC) under grant NE/I028017/1 and partially supported by Boğaziçi University Research Fund (BAP) under grant 6922. We would like to thank all the project members from the University of Leeds, Boğaziçi University, Kandilli Observatory, Aberdeen University and Sakarya University. I would also like to thank Prof. Ali Pinar and Dr. Kıvanç Kekovalı for their valuable comments. Some of the figures were generated by GMT software (Wessel and Smith, 1995).Peer reviewedPostprin

Diagnostic accuracy of fine needle aspiration cytology versus concurrent core needle biopsy in evaluation of intrathoracic lesions: A retrospective comparative study

Background: Transthoracic fine needle aspiration (FNA) cytology and core needle biopsy (CNB) are two commonly used approaches for the diagnosis of suspected neoplastic intrathoracic lesions. This study compared the diagnostic accuracy of FNA cytology and concurrent CNB in the evaluation of intrathoracic lesions. Materials and Methods: We studied FNA cytology and concurrent CNB specimens of 127 patients retrospectively, using hematoxylin and eosin (H&E), immunohistochemistry, and, on certain occasions cytochemistry. Information regarding additional tissue tests was derived from the electronic archives of the Department of Pathology and Laboratory Medicine as well as patient records. Diagnostic accuracy was calculated for each test. Results: Of 127 cases, 22 were inconclusive and excluded from the study. The remaining 105 were categorized into 73 (69.5) malignant lesions and 32 (30.5) benign lesions. FNA and CNB findings were in complete agreement in 63 cases (60). The accuracy and confidence intervals (CIs) of FNA and CNB for malignant tumors were 86.3 (CI: 79.3-90.7) and 93.2 (CI: 87.3-96.0) respectively. For epithelial malignant neoplasms, a definitive diagnosis was made in 44.8 of cases by FNA and 80.6 by CNB. The diagnostic accuracy of CNB for nonepithelial malignant neoplasms was 83.3 compared with 50 for FNA. Of the 32 benign cases, we made specific diagnoses in 16 with diagnostic accuracy of 81.3 and 6.3 for CNB and FNA, respectively. Conclusions: Our findings suggest that FNA is comparable to CNB in the diagnosis of malignant epithelial lesions whereas diagnostic accuracy of CNB for nonepithlial malignant neoplasms is superior to that for FNA. Further, for histological typing of tumors and examining tumor origin, immunohistochemical work up plays an important role

Büyük Menderes Havzasında Organik Pamuk Üretim Olanaklarının Araştırılması

Bu araştırma Büyük Menderes Havzasında Organik Pamuk Üretim Olanaklarının araştırılması amacıyla 2003-2007 yıllarında, Nazilli Pamuk Araştırma Enstitüsünde, tesadüf blokları deneme deseninde, 4 tekrarlamalı yürütülmüştür. Deneme Konuları organik yeşil gübre bitkisi A-arpa, B-arpa+fiğ, C-fiğ(konvansiyonel ekim), D-fiğ(son sulamada ekim) ve E-Kontrol (konvansiyonel pamuk üretim), olarak ele alınmıştır. Araştırmada 2003-2004 yıllarında deneme alanını sömürtmede mısır, 2005-2007 yıllarında organik pamuk üretiminde Nazilli 84-S çeşidi yetiştirilmiştir. Parseller 67,2m² alınmıştır. Deneme parsellerine organik yeşil gübreleme amacıyla Sonbaharda arpa ve fiğ ekilmiş, İlkbaharda pamuk ekim öncesi parçalanıp toprağa karıştırılmıştır. Pamuğa konusuna göre mineral veya organik gübre ve 3-4 sulama uygulanmıştır. Hasat bir defada elle yapılmıştır. Ekim ve hasat dönemlerinde toprağın su ile doymuşluk, toplam tuz%, pH, kireç%, yarayışlı fosfor, yarayışlı potasyum, organik madde %, toplam azot ve Fe,Cu,Zn, Mn,Pb,Cr,Cd,Ni analizleri yapılmıştır. Pamuk parsellerinde fide, koza olgunlaşma, hasat dönemlerinde zararlı ve yabancı ot; %5-10, %50-%60 koza açma döneminde yapraktan; hasattan sonra gövde kesitinde solgunluk hastalık sayımları yapılmıştır. Pamukta verim, çırçır randımanı, uzunluk, incelik, mukavemet analizleri yapılmıştır. Pamuk verim varyans analizinde, konular 2005-2006 yıllarında %99 güvenle farklı, 2007 yılında farksız bulunmuştur. Verimde C-D-E konuları ön sıralarda yer almış, 3 yıllık ortalama verimler sırasıyla 285,4-309,5-293,1 Kg/da olmuştur. Organik pamuk yetiştiriciliğinde organik pamuk verimi ile konvansiyonel pamuk verimi ayni grupta yer almıştır. Sonuçlar Büyük Menderes havzasında organik pamuk yetiştiriciliğinin yapılabilir olduğunu göstermektedir. Bu durum organik tarım ve çevre sağlı açısından büyük önem arz etmektedir

Optical Surface Scanning for Patient Positioning in Radiation Therapy: A Prospective Analysis of 1902 Fractions

Purpose/Objective: Reproducible patient positioning remains one of the major challenges in modern radiation therapy. Recently, optical surface scanners have been introduced into clinical practice in addition to well-established positioning systems, such as room laser and skin marks. The aim of this prospective study was to evaluate setup errors of the optical surface scanner Catalyst HD (C-RAD AB) in different anatomic regions. Material/Methods: Between October 2016 and June 2017 a total of 1902 treatment sessions in 110 patients were evaluated. The workflow of this study included conventional setup procedures using laser-based positioning with skin marks and an additional registration of the 3-dimensional (3D) deviations detected by the Catalyst system. The deviations of the surface-based method were then compared to the corrections of cone beam computed tomography alignment which was considered as gold standard. A practical Catalyst setup error was calculated between the translational deviations of the surface scanner and the laser positioning. Two one-sided t tests for equivalence were used for statistical analysis. Results: Data analysis revealed total deviations of 0.09 mm +/- 2.03 mm for the lateral axis, 0.07 mm +/- 3.21 mm for the longitudinal axis, and 0.44 mm +/- 3.08 mm vertical axis for the Catalyst system, compared to -0.06 +/- 3.54 mm lateral, 0.53 +/- 3.47 mm longitudinal, and 0.19 +/- 3.49 mm vertical for the laser positioning compared to cone beam computed tomography. The lowest positional deviations were found in the cranial region, and larger deviations occurred in the thoracic and abdominal sites. A statistical comparison using 2 one-sided t tests showed a general concordance of the 2 methods (P <= 0.036), excluding the vertical direction of the abdominal region (P=0.198). Conclusion: The optical surface scanner Catalyst HD is a reliable and feasible patient positioning system without any additional radiation exposure. From the head to the thoracic and abdominal region, a decrease in accuracy was observed within a comparable range for Catalyst and laser-assisted positioning

Stability and reproducibility of 6013 deep inspiration breath-holds in left-sided breast cancer

Purpose: Patients with left-sided breast cancer frequently receive deep inspiration breath-hold (DIBH) radiotherapy to reduce the risk of cardiac side effects. The aim of the present study was to analyze intra-breath-hold stability and inter-fraction breath-hold reproducibility in clinical practice. Material and methods: Overall, we analyzed 103 patients receiving left-sided breast cancer radiotherapy using a surface-guided DIBH technique. During each treatment session the vertical motion of the patient was continuously measured by a surface guided radiation therapy (SGRT) system and automated gating control (beam on/off) was performed using an audio-visual patient feedback system. Dose delivery was automatically triggered when the tracking point was within a predefined gating window. Intra-breath-hold stability and inter-fraction reproducibility across all fractions of the entire treatment course were analyzed per patient. Results: In the present series, 6013 breath-holds during beam-on time were analyzed. The mean amplitude of the gating window from the baseline breathing curve (maximum expiration during free breathing) was 15.8 mm (95%-confidence interval: [8.5–30.6] mm) and had a width of 3.5 mm (95%-CI: [2–4.3] mm). As a measure of intra-breath-hold stability, the median standard deviation of the breath-hold level during DIBH was 0.3 mm (95%-CI: [0.1–0.9] mm). Similarly, the median absolute intra-breath-hold linear amplitude deviation was 0.4 mm (95%-CI: [0.01–2.1] mm). Reproducibility testing showed good inter-fractional reliability, as the maximum difference in the breathing amplitudes in all patients and all fractions were 1.3 mm on average (95%-CI: [0.5–2.6] mm). Conclusion: The clinical integration of an optical surface scanner enables a stable and reliable DIBH treatment delivery during SGRT for left-sided breast cancer in clinical routine

MR-guided adaptive stereotactic body radiotherapy (SBRT) of primary tumor for pain control in metastatic pancreatic ductal adenocarcinoma (mPDAC): an open randomized, multicentric, parallel group clinical trial (MASPAC)

BACKGROUND: Pain symptoms in the upper abdomen and back are prevalent in 80% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), where the current standard treatment is a systemic therapy consisting of at least doublet-chemotherapy for fit patients. Palliative low-dose radiotherapy is a well-established local treatment option but there is some evidence for a better and longer pain response after a dose-intensified radiotherapy of the primary pancreatic cancer (pPCa). Stereotactic body radiation therapy (SBRT) can deliver high radiation doses in few fractions, therefore reducing chemotherapy-free intervals. However, prospective data on pain control after SBRT of pPCa is very limited. Therefore, we aim to investigate the impact of SBRT on pain control in patients with mPDAC in a prospective trial. METHODS: This is a prospective, double-arm, randomized controlled, international multicenter study testing the added benefit of MR-guided adaptive SBRT of the pPca embedded between standard of care-chemotherapy (SoC-CT) cycles for pain control and prevention of pain in patients with mPDAC. 92 patients with histologically proven mPDAC and at least stable disease after initial 8 weeks of SoC-CT will be eligible for the trial and 1:1 randomized in 3 centers in Germany and Switzerland to either experimental arm A, receiving MR-guided SBRT of the pPCa with 5 × 6.6 Gy at 80% isodose with continuation of SoC-CT thereafter, or control arm B, continuing SoC-CT without SBRT. Daily MR-guided plan adaptation intents to achieve good target coverage, while simultaneously minimizing dose to organs at risk. Patients will be followed up for minimum 6 and maximum of 18 months. The primary endpoint of the study is the “mean cumulative pain index” rated every 4 weeks until death or end of study using numeric rating scale. DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life. TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT05114213

Box-Cox Regression Method in Time Scaling

Hata terimi ile bağımlı değişkenin süreklilik ve normal dağılma varsayımıbozulduğu durumlarda λj, j = 1, 2, ..., k, kuvvet dönüşümü ile tanımlanan Box-Coxregresyon yöntemi kullanılmaktadır. Y'ler üzerindeki λj, j = 1, 2, ..., k, kuvvetdönüşümünün hangi λj değerinde Hata Kareler Toplamı (HKT)' nı minimum yaptığıdurum ele alınmaktadır. Box-Cox regresyon yöntemi, regresyon fonksiyonunundoğrusal olmayan durumu, sabit olmayan hata varyansları ve hata terimlerinindağılışlarının çarpıklığını düzeltmek için Y'nin üzerinde dönüşüm yapılması açısındanoldukça uygundur. Bu çalışmada fark ve diferansiyel analizin birlikte ele alındığızaman skalası türev kavramı kullanılarak Box-Cox regresyon yöntemi kullanmanınavantaj ve dezavantajları incelenmiştir. Box-Cox regression method with λj, for j = 1, 2, ..., k, power transformation can beused when dependent variable and error term of the linear regression model do notsatisfy the continuity and normality assumptions. The situation obtaining the smallestmean square error when optimum power λj, transformation for j = 1, 2, ..., k, of Y hasbeen discussed. Box-Cox regression method is especially appropriate to adjustexistence skewness or heteroscedasticity of error terms for a nonlinear functionalrelationship between dependent and explanatory variables. In this study, the advantageand disadvantage use of Box-Cox regression method have been discussed indifferentiation and differantial analysis of time scale concept