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Paul van Kempen De zoektocht naar de verdwenen kerk van Weerde in de gemeente Aarschot. [In search of the lost church of Weerde in the city of Aarchot.]Mogelijks één der oudste van Vlaams-Brabant, kende de kerk van Weerde na de godsdienstoorlogen een roemloos einde als steengroeve en brandhout. Ooit gelegen op een donk langsheen eene waterloop ofte laecke, kon haar ligging via karterend bodemonderzoek en geofysisch weerstandsonderzoek heden nauwkeurig worden bepaald.Hoe wetenschappelijk onderzoek aldus de bescherming onderbouwt van archeologische monumenten, wordt door Paul van Kempen in klare taal verhelderd.Marjan Buyle Een reus achter het orgel. Vondst van middeleeuwse muurschilderingen in de Mechelse Sint-Janskerk. [A giant behind the organ. Discovery of mediaeval mural paintings in Saint Johns church in Mechelen.]Als een voorafspiegeling van zijn schrapping uit de heiligenkalender, ging deze Klein-Aziatische reus al sinds mensenheugenis vrijwel onzichtbaar schuil achter het orgel van de Mechelse Sint-Janskerk. Door een dik pakket kalklagen aan het oog onttrokken, hadden deze wél de kleurige temperaschildering van verdere slijtage gevrijwaard.Met nauwelijks verholen enthousiasme brengt Marjan Buyle het relaas van de eerste vaststellingen en stelt ze verdere ontdekkingen in het vooruitzicht.Dieter Nuytten Naar Santiago de Compostella en terug: bouwgeschiedenis en stabiliteitsproblematiek van de Sint-Jacobskerk in Leuven. [To Santiago de Compostella and back: building history and stability problems at Saint Jacobs church in Leuven.]Architectuurhistorisch met haar romaans-gotische overgangsstijl uniek, bleef de Leuvense Sint-Jacobskerk de voorbije 45 jaar nochtans buiten gebruik en ontoegankelijk.De problematische stabiliteit was dan ook geen nieuw feit, maar leidde nog tijdens de bouw rond 1225 tot de eerste urgente interventies.Tegen een emotioneel geladen achtergrond blijft het voor Dieter Nuytten derhalve een heikele onderneming om in het licht van recent stabiliteitsonderzoek hoopgevende perspectieven te formuleren.Summar

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Paul van Kempen en Peter Van den Hove - Archeologisch onderzoek naar het kasteel van Schendelbeke. [An archaeological evaluation of the Schendelbeke castle site.]In 1453 werd het kasteel van Schendelbeke belegerd en ingenomen door het leger van Filips de Goede. Enige genade was er niet: de Gentse bezetters kregen allen de doodstraf en het kasteel werd volledig vernield. Gelegen in een drassig weiland langsheen de Dender ontsnapte de site daarna lange tijd aan alle aandachttot de locatie in de jaren 60 en 70 door enkele lokale heemkundigen werd herontdekt. Archeologen Paul van Kempen en Peter Van den Hove brengen een synthese van oud en nieuw onderzoek naar deze opmerkelijk goed bewaarde archeologische site.Marieke Jaenen - De dierentuin van Antwerpen: een tuin- en bouwhistorisch verhaal. [The Antwerp Zoo: the botanical and architectural history.]Met een ontstaan dat teruggaat tot midden 19de eeuw, biedt de Antwerpse dierentuin thans een staalkaart van oude en nieuwere paviljoenen en tuinaanleg. Marieke Jaenen verdiepte zich in de soms bewogen geschiedenis van de dierentuin en in de evoluerende inzichten en realisaties van de aanleg van de Zoo, waarin het welzijn van de bewoners (de dieren) en de bezoekers altijd de rode draad was. Merkwaardige oude fotos ondersteunen de zoektocht naar het uitzicht en het verleden van deze historische plek.Frank Becuwe en Willem Lanszweert - Het vissersvaartuig OD.1 Martha. [The fishing vessel OD.1 Martha.]Om tijdens Wereldoorlog II tegemoet te komen aan een nijpend gebrek aan vaartuigen om op sprot en haring te vissen, werd in die periode een vloot nieuwe boten gebouwd. Eén daarvan, nu gekend onder de naam OD.1 Martha, werd na talrijke verbouwingen beschermd en gerestaureerd en vormt nu een blikvanger van het Nationaal Visserijmuseum in Oostduinkerke. Frank Becuwe en Willem Lanszweert waren betrokken bij het onderzoek naar de geschiedenis van het vaartuig en bij de museumopstelling en vertellen hoe de Martha uiteindelijk in rustig vaarwater terecht kwam.Summar

Неустойчивость двухслойных течений в проливах Черного моря

Рассмотрена плоская задача о прогрессивных гравитационных внутренних волнах в горизонтальном двухслойном течении Кельвина-Гельмгольца. Найдено аналитическое решение задачи и условия существования внутренних волн. Для течений с параметрами, типичными для пролива Босфор и Керченского пролива, рассчитаны характеристики бароклинных волн. В пространстве волновых чисел определены диапазоны устойчивости и неустойчивости двухслойных течений с характерными для этих проливов параметрами относительно малых возмущений в форме прогрессивных волн.Розглянуто плоску задачу про прогресивні гравітаційні внутрішні хвилі у горизонтальній двошаровій течії Кельвіна-Гельмгольца. Знайдено аналітичне рішення задачі та умови існування внутрішніх хвиль. Для течій з параметрами, типовими для протоки Босфор і Керченської протоки, розраховані характеристики бароклінних хвиль. У просторі хвильових чисел визначені діапазони стійкості і нестійкості двошарових течій з характерними для цих проток параметрами відносно малих збурень у формі прогресивних хвиль.The plane problem of the progressive internal gravity waves in a horizontal two-layer Kelvin-Helmholtz flow is considered. The analytical solution of the problem and the conditions of existence of internal waves are found. For the flows with the typical parameters for the Bosphorus Strait and the Strait of Kerch, characteristics of baroclinic waves are calculated. The stability and instability regimes of two-layer currents with characteristic parameters of these straits with respect to small wave disturbances are found in the space of wave numbers

Comparison of Circulating Cell-Free DNA Extraction Methods for Downstream Analysis in Cancer Patients

Circulating cell-free DNA (ccfDNA) may contain DNA originating from the tumor in plasma of cancer patients (ctDNA) and enables noninvasive cancer diagnosis, treatment predictive testing, and response monitoring. A recent multicenter evaluation of workflows by the CANCER-ID consortium using artificial spiked-in plasma showed significant differences and consequently the importance of carefully selecting ccfDNA extraction methods. Here, the quantity and integrity of extracted ccfDNA from the plasma of cancer patients were assessed. Twenty-one cancer patient-derived cell-free plasma samples were selected to compare the Qiagen CNA, Maxwell RSC ccfDNA plasma, and Zymo manual quick ccfDNA kit. High-volume citrate plasma samples collected by diagnostic leukapheresis from six cancer patients were used to compare the Qiagen CNA (2 mL) and QIAamp MinElute ccfDNA kit (8 mL). This study revealed similar integrity and similar levels of amplified short-sized fragments and tumor-specific mutants comparing the CNA and RSC kits. However, the CNA kit consistently showed the highest yield of ccfDNA and short-sized fragments, while the RSC and ME kits showed higher variant allelic frequencies (VAFs). Our study pinpoints the importance of standardizing preanalytical conditions as well as consensus on defining the input of ccfDNA to accurately detect ctDNA and be able to compare results in a clinical routine practice, within and between clinical studies

Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors

Immunotherapy for metastasized non-small-cell lung cancer (NSCLC) can show long-lasting clinical responses. Selection of patients based on programmed death-ligand 1 (PD-L1) expression shows limited predictive value for durable clinical benefit (DCB). We investigated whether early treatment effects as measured by a change in circulating tumor DNA (ctDNA) level is a proxy of early tumor response to immunotherapy according to response evaluation criteria in solid tumors v1.1 criteria, progression-free survival (PFS), DCB, and overall survival (OS). To this aim, blood tubes were collected from advanced-stage lung adenocarcinoma patients (n = 100) receiving immune checkpoint inhibitors (ICI) at baseline (t(0)) and prior to first treatment evaluation (4-6 weeks; t(1)). Nontargetable (driver) mutations detected in the pretreatment tumor biopsy were used to quantify tumor-specific ctDNA levels using droplet digital PCR. We found that changes in ctDNA levels were strongly associated with tumor response. A > 30% decrease in ctDNA at t(1) correlated with a longer PFS and OS. In total, 80% of patients with a DCB of >= 26 weeks displayed a > 30% decrease in ctDNA levels. For patients with a PD-L1 tumor proportion score of >= 1%, decreasing ctDNA levels were associated with a higher frequency a DCB (80%) and a prolonged median PFS (85 weeks) and OS (101 weeks) compared with patients with no decrease in ctDNA (34%; 11 and 39 weeks, respectively). This study shows that monitoring of ctDNA dynamics is an easy-to-use and promising tool for assessing PFS, DCB, and OS for ICI-treated NSCLC patients

Satellite observations reveal extreme methane leakage from a natural gas well blowout

Methane emissions due to accidents in the oil and natural gas sector are very challenging tomonitor, and hence are seldomconsidered in emission inventories and reporting. One of the main reasons is the lack of measurements during such events. Here we report the detection of large methane emissions from a gas well blowout in Ohio during February to March 2018 in the total column methane measurements from the spaceborne Tropospheric Monitoring Instrument (TROPOMI). From these data, we derive a methane emission rate of 120 ± 32 metric tons per hour. This hourly emission rate is twice that of the widely reported Aliso Canyon event in California in 2015. Assuming the detected emission represents the average rate for the 20-d blowout period, we find the total methane emission from the well blowout is comparable to one-quarter of the entire state of Ohio's reported annual oil and natural gas methane emission, or, alternatively, a substantial fraction of the annual anthropogenic methane emissions from several European countries. Our work demonstrates the strength and effectiveness of routine satellite measurements in detecting and quantifying greenhouse gas emission from unpredictable events. In this specific case, the magnitude of a relatively unknown yet extremely large accidental leakage was revealed using measurements of TROPOMI in its routine global survey, providing quantitative assessment of associated methane emissions

FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Introduction Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. Methods Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. Results FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p . 0.05). Conclusion FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients

A Micro-Costing Framework for Circulating Tumor DNA Testing in Dutch Clinical Practice

Circulating tumor DNA (ctDNA) is a promising new biomarker with multiple potential applications in cancer care. Estimating total cost of ctDNA testing is necessary for reimbursement and implementation, but challenging because of variations in workflow. We aimed to develop a micro-costing framework for consistent cost calculation of ctDNA testing. First, the foundation of the framework was built, based on the complete step-wise diagnostic workflow of ctDNA testing. Second, the costing method was set up, including costs for personnel, materials, equipment, overhead, and failures. Third, the framework was evaluated by experts and applied to six case studies, including PCR-, mass spectrometry–, and next-generation sequencing–based platforms, from three Dutch hospitals. The developed ctDNA micro-costing framework includes the diagnostic workflow from blood sample collection to diagnostic test result. The framework was developed from a Dutch perspective and takes testing volume into account. An open access tool is provided to allow for laboratory-specific calculations to explore the total costs of ctDNA testing specific workflow parameters matching the setting of interest. It also allows to straightforwardly assess the impact of alternative prices or assumptions on the cost per sample by simply varying the input parameters. The case studies showed a wide range of costs, from €168 to €7638 ($199 to$9124) per sample, and generated information. These costs are sensitive to the (coverage of) platform, setting, and testing volume

Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients

PURPOSE: In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. METHODS: In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. RESULTS: As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. CONCLUSIONS: With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events