Development and multicenter validation of a multiparametric imaging model to predict treatment response in rectal cancer

Funding Information: This study has received funding from the Dutch Cancer Society (project number 10138). Publisher Copyright: © 2023, The Author(s).Objectives: To develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset. Methods: Baseline staging MRIs (T2W (T2-weighted)-MRI, diffusion-weighted imaging (DWI) / apparent diffusion coefficient (ADC)) of 509 patients (9 centres) treated with neoadjuvant chemoradiotherapy (CRT) were collected. Response was defined as (1) complete versus incomplete response, or (2) good (Mandard tumor regression grade (TRG) 1–2) versus poor response (TRG3-5). Prediction models were developed using combinations of the following variable groups: (1) Non-imaging: age/sex/tumor-location/tumor-morphology/CRT-surgery interval (2) Basic staging: cT-stage/cN-stage/mesorectal fascia involvement, derived from (2a) original staging reports, or (2b) expert re-evaluation (3) Advanced staging: variables from 2b combined with cTN-substaging/invasion depth/extramural vascular invasion/tumor length (4) Quantitative imaging: tumour volume + first-order histogram features (from T2W-MRI and DWI/ADC) Models were developed with data from 6 centers (n = 412) using logistic regression with the Least Absolute Shrinkage and Selector Operator (LASSO) feature selection, internally validated using repeated (n = 100) random hold-out validation, and externally validated using data from 3 centers (n = 97). Results: After external validation, the best model (including non-imaging and advanced staging variables) achieved an area under the curve of 0.60 (95%CI=0.48–0.72) to predict complete response and 0.65 (95%CI=0.53–0.76) to predict a good response. Quantitative variables did not improve model performance. Basic staging variables consistently achieved lower performance compared to advanced staging variables. Conclusions: Overall model performance was moderate. Best results were obtained using advanced staging variables, highlighting the importance of good-quality staging according to current guidelines. Quantitative imaging features had no added value (in this heterogeneous dataset). Clinical relevance statement: Predicting tumour response at baseline could aid in tailoring neoadjuvant therapies for rectal cancer. This study shows that image-based prediction models are promising, though are negatively affected by variations in staging quality and MRI acquisition, urging the need for harmonization. Key Points: This multicenter study combining clinical information and features derived from MRI rendered disappointing performance to predict response to neoadjuvant treatment in rectal cancer. Best results were obtained with the combination of clinical baseline information and state-of-the-art image-based staging variables, highlighting the importance of good quality staging according to current guidelines and staging templates. No added value was found for quantitative imaging features in this multicenter retrospective study. This is likely related to acquisition variations, which is a major problem for feature reproducibility and thus model generalizability.Peer reviewe

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

A health economic model for evaluating a vaccine for the prevention of herpes zoster and post-herpetic neuralgia in the UK

<p>Abstract</p> <p>Background</p> <p>A live-attenuated vaccine aimed at preventing herpes zoster (HZ) and its main complication, post-herpetic neuralgia (PHN) is available in Europe for immunocompetent adults aged 50 years and more. The study objective is to assess the cost effectiveness of a vaccination program for this population in the UK.</p> <p>Methods</p> <p>A state-transition Markov model has been developed to simulate the natural history of HZ and PHN and to estimate the lifetime effects of vaccination in the UK. Several health states are defined including good health, HZ, PHN, and death. HZ and PHN health states are further divided to reflect pain severity.</p> <p>Results</p> <p>The model predicts that a vaccination strategy for those aged over 50 years would lead to an incremental cost-effectiveness ratio of £13,077 per QALY gained from the NHS perspective, when compared to the current strategy of no vaccination. Age-group analyses show that the lowest ICERs (£10,984 and £10,275 for NHS) are observed when vaccinating people between 60-64 and 65-69 years of age. Sensitivity analyses showed that results are sensitive to the duration of vaccine protection, discount rate, utility decrements and pain severity split used.</p> <p>Conclusions</p> <p>Using the commonly accepted threshold of £30,000 per QALY gained in the UK, most scenarios of vaccination programmes preventing HZ and PHN, including the potential use of a repeat dose, may be considered cost-effective by the NHS, especially within the 60 to 69 age-groups.</p

Langages de l'utopie dans les revues de femmes (1970-1980)

Doctorat en philosophie et lettresinfo:eu-repo/semantics/nonPublishe

Langages de l'utopie dans les revues de femmes (1970-1980)

Doctorat en philosophie et lettresinfo:eu-repo/semantics/nonPublishe

1859 et la naissance de l'archéologie préhistorique en Normandie.

En 1859, l'archéologie normande s'exerce dans un cadre partiellement structuré par des liens avec des institutions administratives et des sociétés savantes dynamiques dont certaines, animées en particulier par Arcisse de Caumont, ont une dimension nationale. Si cette archéologie est avant tout historique, les débats sur l'ancienneté de l'homme et les questions chronologiques n'y sont pas ignorés de certains savants dès les années 1850. Face aux « événements » de la Somme, des réactions différentes se manifestent : intervention directe et adhésion rapide du jeune naturaliste Pouchet et de l'abbé Cochet, archéologue renommé, mais réticences prolongées jusqu'en 1867 de Caumont qui contribuent au silence largement dominant alors dans les publications normandes. Le rapprochement entre leurs articles et leurs correspondances révèle par ailleurs une plus grande complexité de la situation. Des différences, voire des oppositions, sont nettement perceptibles chez ces trois hommes - un médecin, intéressé par l'anthropologie et deux archéologues historiens. Elles concernent à la fois leurs attitudes intellectuelles face au débat de fond –l'antiquité et l'évolution de l'homme- et leurs pratiques mais tous trois montrent une certaine capacité à se remettre en cause. Leurs actions s'inscrivent non seulement dans un contexte régional large, à la fois scientifique et social, mais aussi assez nettement en réaction face aux milieux culturels parisiens et en liaison avec des savants anglais avec lesquels les relations sont déjà anciennes. Ce temps qui voit la « naissance » de l'archéologie préhistorique en Normandie lui confère certains caractères, plus ou moins durables, avant un second moment d'impulsion et de mutation autour de la tenue, en 1877, au Havre, du congrès de l'AFAS accompagné d'une grande exposition géologique et paléontologique, organisée par la Société Géologique de Normandie, dans laquelle la préhistoire régionale a sa place

Le rôle de la Haute-Normandie dans les problématiques préhistoriques du XIXe siècle : chronologie et stratigraphie du paléolithique inférieur et moyen (1870-1894)

L’examen des recherches menées en Haute-Normandie durant la première période de construction de la préhistoire permet d’étudier les débats concernant les débuts du Paléolithique, avec leurs contradictions, aux échelles à la fois régionale et nationale, des interactions existant entre les deux. Des moments privilégiés marquent ce processus : congrès de l’Association française pour l’avancement des sciences du Havre (1877) puis de Rouen (1883) et fondation de la Société normande d’études préhistoriques (1893).The role of Haute-Normandie in the prehistoric issues of the 19th Century: the chronology and stratigraphy of the Lower and Middle Paleolithic (1870-1894) By examining research carried out in Haute-Normandie during the initial construction of prehistory, it is possible to study debates concerning the beginnings of the Paleolithic Period, along with their contradictions, both on a regional and national scale, and the interlinkages that exist between the two. Some important moments characterise this process: the French Association for the Advancement of Science congress in le Havre (1877), and subsequently in Rouen (1883), and the foundation of the Norman Society of Prehistoric Studies (1893)

Un des premiers préhistoriens de Normandie : l'abbé Deshayes (1844-1910)

The abbé Deshayes (1844-1910) was one of the first prehistorians of Normandy. He worked chiefly in Risle valley (Eure). He early organized the almost systematic prospection of a more specific district : Manneville-sur-Risle. Moreover, it is interesting to study at once, by means of his case, the thinking of a man, both priest and prehistorian, and the matter of private collections which were important at that time.L'abbé Deshayes (1844-1910), un des premiers préhistoriens normands, a travaillé surtout dans la vallée de la Risle (Eure). Il a en particulier organisé précocement une prospection quasi systématique du territoire d'une commune : Manneville-sur-Risle. Il est intéressant par ailleurs d'examiner, à travers son cas, le mode de pensée d'un prêtre préhistorien et la question des collections particulières dont le rôle était important à cette époque