Molecular Fluorescence Endoscopy:clinical development and validation within the lower gastrointestinal tract

Molecular Fluorescence Imaging is a new and evolving imaging technique. It uses exogenous fluorescent tracers that bind to specific proteins, thereby fluorescently highlighting the tissue of interest as a red-flag for the clinician. White-light endoscopy is the current gold standard for colorectal adenoma and cancer screening, where gastroenterologist evaluate aberrant tissue based on morphological aspects and architectural changes only. As adenoma miss rates in colonoscopy are unacceptably high, especially in high-risk populations, we describe in this thesis a clinical dose-escalation study towards the use of Molecular Fluorescence Endoscopy for colorectal adenoma detection. This technique showed to have the potential to improve the identification of colorectal adenomas. In the second part of this thesis, the added value of a restaging CT scan after neoadjuvant chemoradiotherapy is shown for patients with locally advanced rectal cancer, as it may detect newly developed metastases. In a clinical study, the potential of Molecular Fluorescence Endoscopy as tool to aid clinical response assessment is shown, in patients with locally advanced rectal cancer. When this technique is performed after neoadjuvant chemoradiotherapy, it can help identifying the presence of residual tumor and has potential to predict pathological compete response (pCR) and in this way help selecting patients suitable for organ-preserving strategies. Additionally, we show in a proof-of-concept study that molecular fluorescence imaging performed peri-operative can help the surgeon evaluating the circumferential resection margin at the surgical theatre, preventing under- and overtreatment of patients in the future

Q Fever

Q fever was first identified in Iowa, in both man and animal, in 1957. Subsequently the disease was demonstrated to occur enzootic ally among Iowa dairy cattle and, perhaps more important, constitute an occupational hazard of some degree for farmers and certain industrial groups in the state

Predicting a noisy signal: the costs and benefits of time averaging as a noise mitigation strategy

One major challenge for living cells is the measurement and prediction of signals corrupted by noise. In general, cells need to make decisions based on their compressed representation of noisy, time-varying signals. Strategies for signal noise mitigation are often tackled using Wiener filtering theory, but this theory cannot account for systems that have limited resources and hence must compress the signal. To study how accurately linear systems can predict noisy, time-varying signals in the presence of a compression constraint, we extend the information bottleneck method. We show that the optimal integration kernel reduces to the Wiener filter in the absence of a compression constraint. This kernel combines a delta function at short times and an exponential function that decays on a timescale that sets the integration time. Moreover, there exists an optimal integration time, which arises from a trade-off between time averaging signal noise and dynamical error. As the level of compression is increased, time averaging becomes harder, and as a result the optimal integration time decreases and the delta peak increases. We compare the behaviour of the optimal system with that of a canonical motif in cell signalling, the push-pull network, finding that the system reacts to signal noise and compression in a similar way

Burning of an ulcerated breast cancer during MRI: A lesson to be learned

The use of a breast magnetic resonance imaging (MRI) in the evaluation of cancer is increasing. The absolute contraindications for MRI are well known. Lesser know are the thermal injuries or burns caused by MRI. During a recent breast MRI of a patient with an ulcerated locally advanced breast cancer we did a remarkable observation. Almost directly from the start of the MRI the patient felt a slowly increasing excitation in the left breast together with a warm feeling. Within a few minutes she had the feeling that her left breast was burning. The MRI was stopped and the burning sensation diminished. The MRI was cancelled and no direct cause was found. It was only the next day during the ward round when inspecting her wound that we realized that the zinc oxide ointment, which was used for her wound care, was the likely course of her burning

Effective bet-hedging through growth rate dependent stability

Microbes in the wild face highly variable and unpredictable environments and are naturally selected for their average growth rate across environments. Apart from using sensory regulatory systems to adapt in a targeted manner to changing environments, microbes employ bet-hedging strategies where cells in an isogenic population switch stochastically between alternative phenotypes. Yet, bet-hedging suffers from a fundamental trade-off: Increasing the phenotype-switching rate increases the rate at which maladapted cells explore alternative phenotypes but also increases the rate at which cells switch out of a well-adapted state. Consequently, it is currently believed that bet-hedging strategies are effective only when the number of possible phenotypes is limited and when environments last for sufficiently many generations. However, recent experimental results show that gene expression noise generally decreases with growth rate, suggesting that phenotype-switching rates may systematically decrease with growth rate. Such growth rate dependent stability (GRDS) causes cells to be more explorative when maladapted and more phenotypically stable when well-adapted, and we show that GRDS can almost completely overcome the trade-off that limits bet-hedging, allowing for effective adaptation even when environments are diverse and change rapidly. We further show that even a small decrease in switching rates of faster-growing phenotypes can substantially increase long-term fitness of bet-hedging strategies. Together, our results suggest that stochastic strategies may play an even bigger role for microbial adaptation than hitherto appreciated

National guidelines for management of cervical squamous intraepithelial lesion : A survey of European Federation for Colposcopy members

Acknowledgements: Austria: Olaf Reich: Belgium: Wiebrin Tjalma; Croatia: Drazan Butorac; Cyprus: Dinos Mavromoustakis; Estonia: Terje Raud, Liis Kriisa; Finland: Maija Jakobsson;bFrance: Xavier Carcopino; Georgia: Tamar Alibegashvili; Germany: Jens Quaas Volkmar Kuppers, Greece: Georgios Michail; Hungary: Robert Koiss; Iceland: Kristjan Oddsson; Ireland: Grainne Flannelly; Israel: Efraim Siegler; Italy: Andrea Ciavattini; Kosovo: Mazllom Smajli; Latvia: Kristine Pcolkina; Lithuania: Kristina Jariene; Macedonia: Goran Dimitrov; Moldova: Uliana Tabuica; Norway: Amelie Tropé; Poland: Robert Jach; Portugal: Amélia Pedro; Romania: Mihaela Grigore Russia: Vera Prilepskaya; Serbia: Vesna Kesic; Slovenia: Spela Smrkolj ; Spain: Marta del Pino; Sweden: Björn Strander; Switzerland: André Kind, Brigitte Frey Tirri; The Netherlands: A.M.L.D. van Haaften-de Jong; Turkey: Murat Gultekin; U.K.: Pierre Martin-Hirsch; Ukraine: Nataliya VolodkoPeer reviewedPostprin

Validation of liquid biopsy for ESR1-mutation analysis in hormone-sensitive breast cancer: a pooled meta-analysis

Several retrospective and prospective studies have shown that genomic alterations in Estrogen-receptor one (ESR1) can be characterized not only in tissue samples but also by sequencing circulating tumor DNA (ctDNA) in liquid biopsy. Therefore, liquid biopsy is a potential noninvasive surrogate for tissue biopsy. This meta-analysis was designed to compare the prevalence of ESR 1 mutation detected with liquid biopsy and tissue biopsy. A pooled meta-analysis of studies published between 1 January 2007 and 1 March 2021 was conducted regarding the methodologies used for ESR1 mutation analysis. Liquid biopsy is a valid, inexpensive, and attractive noninvasive alternative to tumor biopsies for the identification of ESR1 mutations. Liquid biopsy for ESR 1 analysis would facilitate regular testing, allowing monitoring of the sensitivity to ET and guiding treatment strategies