Université de Caen Normandie

Radiation biology is the study of the effects of ionizing radiation on biological tissues and living organisms. It combines radiation physics and biology. The purpose of this chapter is to introduce the terminology and basic concepts of radiobiology to create a better understanding of the ionizing radiation interactions with a living organism. This chapter firstly describes the different types of radiation, the sources, and the radiation interactions with matter. The basic concepts of radioactivity and its applications are also included. Ionizing radiation causes significant physical and chemical modifications, which eventually lead to biological effects in the exposed tissue or organism. The physical quantities and units needed to describe the radiation are introduced here. Eventually, a broad range of biological effects of the different radiation types are addressed. This chapter concludes with a specific focus on the effects of low doses of radiation.

In this chapter, we address the role of radiation as treatment modality in the context of oncological treatments given to patients. Physical aspects of the use of ionizing radiation (IR)—by either photons, neutrons, or charged (high linear energy transfer) particles—and their clinical application are summarized. Information is also provided regarding the radiobiological rationale of the use of conventional fractionation as well as alternative fractionation schedules using deviating total dose, fraction size, number of fractions, and the overall treatment time. Pro- and contra arguments of hypofractionation are discussed. In particular, the biological rationale and clinical application of Stereotactic Body Radiation Therapy (SBRT) are described. Furthermore, background information is given about FLASH radiotherapy (RT), which is an emerging new radiation method using ultra-high dose rate allowing the healthy, normal tissues and organs to be spared while maintaining the antitumor effect. Spatial fractionation of radiation in tumor therapy, another method that reduces damage to normal tissue is presented. Normal tissue doses could also be minimized by interstitial or intraluminal irradiation, i.e., brachytherapy, and herein an overview is given on the principles of brachytherapy and its clinical application. Furthermore, details are provided regarding the principles, clinical application, and limitations of boron neutron capture therapy (BNCT). Another important key issue in cancer therapy is the combination of RT with other treatment modalities, e.g., chemotherapy, targeted therapy, immunotherapy, hyperthermia, and hormonal therapy. Combination treatments are aimed to selectively enhance the effect of radiation in cancer cells or to trigger the immune system but also to minimize adverse effects on normal cells. The biological rationale of all these combination treatments as well as their application in clinical settings are outlined. To selectively reach high concentrations of radionuclides in tumor tissue, radioembolization is a highly interesting approach. Also, radioligand therapy which enables specific targeting of cancer cells, while causing minimal harm surrounding healthy tissues is presented. A brief overview is provided on how nanotechnology could contribute to the diagnosis and treatment of cancer. Last but not least, risk factors involved in acquiring secondary tumors after RT are discussed.

In a recent paper we proved some new bounded height results for equations involving varying integer exponents. Here we make a start on the problem of generalizing to rational exponents, which corresponds to the step from groups that are finitely generated to groups of finite rank. We discover two unexpected obstacles. The first is that bounded height may genuinely fail in the neighbourhood of certain exponents. The second concerns vanishing subsums, which seem to be much harder to deal with than in classical situations like S-unit equations. But for certain simple and natural equations we are able to clarify the first obstacle and eliminate the second. The proofs are partly based on our earlier work but there are also new considerations about successive minima over function fields.

Electrical vagus nerve stimulation (eVNS) comprises an array of non-pharmacologic techniques used to stimulate afferent fibers of the vagus nerve. Despite the increasing use of eVNS both in clinical settings and in research, there is still a need for a valid biological marker that can be used to indicate the action of eVNS in the central as well as in the peripheral nervous system. The present chapter focuses on one of the most prominent candidates for such a biomarker, namely, heart rate variability (HRV). We provide arguments for the s of specific HRV parameters to this aim, namely, vagally-mediated HRV, which reflects cardiac vagal activity. We describe the mechanism of action underlying the expected effects of eVNS on cardiac vagal activity and perform a literature review, which shows mixed evidence on the increase of cardiac vagal activity due to eVNS. Furthermore, we point out relevant methodological caveats of current literature on eVNS and discuss how to avoid them in a study designed to investigate the relationship between eVNS and cardiac vagal activity. Based on this, we describe what is necessary to properly measure cardiac vagal activity during the use of eVNS, and discuss considerations that need to be observed when it comes to designing studies that aim to address this relationship.

This study outlines the development of novel boronic acids as catalysts for the direct synthesis of amides from carboxylic acids and amines. The Lewis acidity of the boronic acids was estimated by means of computational techniques, and the observed increase in catalytic activity was corroborated by kinetic data derived from a model reaction. Our investigations led to the discovery of a set of ortho‐(sulfonyloxy)benzeneboronic acids that compared favorably with the established state‐of‐the‐art. These newly developed catalysts demonstrated efficacy in the coupling of aliphatic, aromatic, and heteroaromatic acids, as well as primary and secondary amines.

Background Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient’s tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients. Method The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model. Discussion This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation. Trial registration The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.

Antibiotic resistance is one of the greatest public health challenges of our time. International efforts to curb resistance have largely focused on drug development and limiting unnecessary antibiotic use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, we propose that bacterial flow between humans and animals can exacerbate the emergence and spread of resistant pathogens. Here, we describe the consequences of poor environmental controls by comparing mobile resistance elements among Escherichia coli recovered from humans and meat in Cambodia, a middle-income country with substantial human–animal connectivity and unregulated antibiotic use. We identified identical mobile resistance elements and a conserved transposon region that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human–animal interfaces should be a critical part of addressing antibiotic resistance in low- and especially middle-income countries.

Background Although Carotid Web (CaW) is increasingly diagnosed as a cause of cryptogenic stroke, data are still limited to monocentric small sample cohort. To broaden knowledge on symptomatic carotid web (CaW), CAROWEB registry has been recently implemented. Aims In a large cohort of symptomatic CaW patients, we described epidemiologic characteristics, admission clinical and imaging features, and the current management including the secondary preventive strategy choice made in comprehensive French Stroke Units. Methods CAROWEB is an ongoing French observational multicenter registry enrolling consecutive CaW patients diagnosed after an ipsilateral ischemic stroke (IS) or transient ischemic attack (TIA). Submitted cases were validated by two experienced neurologist and neuroradiologist. Clinical, imaging and management features were collected for this study. Results Between June, 2019 and December, 2021, 244 cases were submitted by 14 centers, 42 rejected and 202 included (IS, 91.6%; TIA, 7.9%; retinal infarction, 0.5%; mean age, 50.8±12.2 years; female, 62.9%; Caucasian, 47.5%; Afro-Caribbean, 20.3%). IS patients showed: median (IQR) admission NIHSS score, 8 (2-15); intracranial artery occlusion, 71.8%; ipsilateral chronic cerebral infarction (CCI), 16.3%; reperfusion treatment, 57.3%. CaW was not identified during the mechanical thrombectomy procedure in 30/85 (35.3%). Secondary prevention was invasive in 55.6% (stenting, n=80; surgery, n=30). In multivariable analysis, the invasive therapeutic option was associated with ipsilateral CCI (OR:4.24 [1.27-14.2], p=0.019) and inversely associated with risk factors (OR:0.47, [0.24-0.91], p=0.0255), and admission NIHSS score (OR:0.93, [0.89-0.97], p=0.0012). Conclusion CaW must be considered in all ethnic groups included Caucasians. Secondary prevention is heterogeneous in large French Stroke Centers. Absence of risk factors, milder severity strokes and ipsilateral CCI were predictive variables of secondary invasive treatment. The high rate of invasive treatment suggest that medical treatment alone is deemed ineffective to avoid recurrence and emphasize the need of randomized trials. Data Access Statement Anonymized database used for these analyses are available from the corresponding author upon reasonable written request.

In this paper, we propose a new generalization of the zero-truncated negative binomial distribution using the Lagrange expansion of the second kind, which we call the Lagrangian zero-truncated negative binomial distribution (LZTNBD). The proposed distribution’s formulation and properties, including its mean, variance, skewness, kurtosis, factorial moment, and index of dispersion, are studied. Because of the various shapes of the hazard rate function, the new distribution reveals great flexibility. Using the equivalence theorem of the class of Lagrangian distribution, we show that the LZTNBD belongs to the Lagrangian family of the first kind. We estimate the unknown parameters of the LZTNBD using the method of maximum likelihood. The performance of the estimates is evaluated through a broad simulation study. We employ the mean-parameterized form of the LZTNBD to present a novel count regression model that is apt for both overdispersed and underdispersed situations. To further illustrate the relevance and applicability of the proposed model, real-world data sets are employed.

Coastal boulder deposits (CBDs), named huracanolitos in Cuba, found along rocky shores, result from storms, tropical cyclones or tsunamis. Despite being important indicators for coastal hazard assessment, determining the mode of emplacement of CBDs (storm/hurricane or tsunami) is not easy. We present, for the first time in English, data about CBDs along the shores of the Cuban Archipelago. More specifically, we focused on a CBD, that is, to our knowledge, the largest one ever described on Cuba Island. Located on a low‐lying coral reef terrace on the SE shore of the island, the reefal limestone CBD is emplaced seaward of the ruins of the Bucanero resort. The resort was built in 1989, endured hurricanes Ivan (2004) and Dennis (2005) and, in October 2012, was destroyed by Hurricane Sandy. As observed on Corona and Landsat satellite images since 1962, the CBD was not moved, neither by hurricane Flora (1963) nor Sandy (2012), both associated with important storm surges and powerful swells. We determined the CBD volume with open‐source structure from motion photogrammetry as 82.6 m ³ . Then, we estimated from a sample its density as 2550 kg/m ³ . Finally we calculated its weight as 210.6 tons. We calculated the minimum flow velocity responsible for the emplacement of the CBD 33 ± 2 m inland—6.83 ± 0.54 m/s and 7.26 ± 0.51 m/s. Such flow velocities are compatible with those of both tsunamis and hurricanes. Because of the greater frequency of hurricanes than tsunamis in the area, we propose that a tropical cyclone generated the extreme surge and wave that emplaced the Bucanero CBD. Such CBDs demonstrate that on Cuba's south coast, we can expect marine flooding exceeding the flooding during the major hurricanes of recent decades.

Fungal detection in equine airways may be performed on either tracheal wash (TW) or bronchoalveolar lavage fluid (BALF) by either cytology or culture. However, method comparisons are sparse. Our objective was to determine the prevalence of fungi in airways of horses according to the sample site and laboratory methodology. Sixty-two adult horses, investigated in the field or referred for respiratory disease, were included. Tracheal wash, and BALF collected separately from both lungs, were collected using a videoendoscope. Fungi were detected in cytologic samples examined by light microscopy, and by fungal culture. Hay was sampled in the field. Prevalence of fungi was of 91.9% in TW and 37.1% in BALF. Fungi were cultured from 82.3% of TW and 20.9% of BALF. Fungal elements were observed cytologically in 69.4% of TW and 22.6% of BALF. In 50% of horses, the same fungi were detected in both TW and hay, but fungi detected in BALF and hay differed in all horses. Poor agreement was found for the detection of fungi between TW and BALF and between fungal culture and cytologic examination (Cohen's kappa coefficient (κ) < 0.20). Moderate agreement was found between cytologic examination of left and right lungs (κ = 0.47). The prevalence of fungi detected cytologically on pooled BALF was significantly different (p = 0.023) than on combined left and right BALF. Fungi were more prevalent in the TW than BALF, and results suggest that hay might not be the primary source of fungi of the lower respiratory tract of horses.

Aim: Trait-based approaches are powerful to examine the processes associated with biological invasions. Functional comparison among native and non-indigenous species (NIS) can notably infer whether novel assemblages result from neutral or niche-based assembly rules. Applying such a framework to biofouling communities, our study aimed to elucidate their distributions within two marine urban habitats (namely floating vs. nonfloating habitats). Location: Southeast Pacific-Central Chilean coastline. Methods: Here, we examined the distribution of 12 functional traits in fouling communities established on settlement plates, after 3 and 13 months of deployment in the two habitats and across ports in Central Chile. Based upon previously described differences of assemblages and NIS contribution across habitats, we hypothesized that nonindigenous, cryptogenic and native taxon pools would be functionally distinct (and trait biased), and that functional diversity and structure would vary across habitats and successional stages. Results: Our results show, as anticipated, that nonindigenous (13 taxa), cryptogenic (12) and native (18) taxon pools are functionally distinct, though overlapping in the trait space. Non-indigenous species are rather related to colonizing traits, while native species are more related to competitive traits. Only one widespread NIS was functionally similar to the late successional and most competitive native species, including taxa elsewhere invasives. Despite differences in taxonomic composition between habitats, we did not observe functional differences between them. In contrast, temporal variations across colonization stages were detected along with an increased contribution in large and long-lived taxa, together with site-specific trajectories. Main Conclusions: We conclude that the functional distinctness among nonindige-nous, cryptogenic and native taxa occupying artificial habitats in ports reflects niche-based processes. Site-specific trajectories indicate that scale-dependent assembly processes, such as dispersal and species interactions, are at play.

The half-logistic (HL) distribution is a widely considered statistical model for studying lifetime phenomena arising in science, engineering, finance, and biomedical sciences. One of its weaknesses is that it has a decreasing probability density function and an increasing hazard rate function only. Due to that, researchers have been modifying the HL distribution to have more functional ability. This article provides an extensive overview of the HL distribution and its generalization (or extensions). The recent advancements regarding the HL distribution have led to numerous results in modern theory and statistical computing techniques across science and engineering. This work extended the body of literature in a summarized way to clarify some of the states of knowledge, potentials, and important roles played by the HL distribution and related models in probability theory and statistical studies in various areas and applications. In particular, at least sixty-seven flexible extensions of the HL distribution have been proposed in the past few years. We give a brief introduction to these distributions, emphasizing model parameters, properties derived, and the estimation method. Conclusively, there is no doubt that this summary could create a consensus between various related results in both theory and applications of the HL-related models to develop an interest in future studies.

New therapeutic approaches are needed for the management of the highly chemo- and radioresistant chondrosarcoma (CHS). In this work, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the intracellular delivery of the chemotherapeutic doxorubicin (IONP DOX ) to augment the cytotoxic effects of carbon ions in comparison to photon radiation therapy. The in vitro biological effects were investigated in SW1353 chondrosarcoma cells focusing on the following parameters: cell survival using clonogenic test, detection of micronuclei (MN) by cytokinesis blocked micronucleus assay and morphology together with spectral fingerprints of nuclei using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module. The combination of IONP DOX with ion carbon or photon irradiation increased the lethal effects of irradiation alone in correlation with the induction of MN. Alterations in the hyperspectral images and spectral profiles of nuclei reflected the CHS cell biological modifications following the treatments, highlighting possible new spectroscopic markers of cancer therapy effects. These outcomes showed that the proposed combined treatment is promising in improving CHS radiotherapy.

Importance Compared with term-born peers, children born very preterm generally perform poorly in executive functions, particularly in working memory and inhibition. By taking advantage of neuroplasticity, computerized cognitive training of working memory in those children could improve visuospatial processing by boosting visual inhibition via working memory. Objective To evaluate the long-term effect of cognitive working memory training on visuospatial processing in children aged 5½ to 6 years born very preterm who have working memory impairment. Design, Setting, and Participants This multicenter (18 French university hospitals), open-label randomized clinical trial with 2 parallel groups (EPIREMED) was conducted from November 2016 to April 2018, with the last follow-up during August 2019. Eligible children from the EPIPAGE 2 cohort were aged 5½ to 6 years, were born between 24 and 34 weeks’ gestation, and had a global intelligence quotient greater than 70 and a working memory index less than 85. Data were analyzed from February to December 2020. Intervention Children were randomized 1:1 to standard care management and a working memory cognitive training program (Cogmed software) for 8 weeks (25 sessions) (intervention) or to standard management (control). Main Outcomes and Measures The primary outcome was the visuospatial index score from the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition. Secondary outcomes were working memory, intellectual functioning, executive and attention processes, language skills, behavior, quality of life, and schooling. Neurobehavioral assessments were performed at inclusion and after finishing training at 6 months (intermeditate assessment; secondary outcomes) and at 16 months (final assessment; primary outcome). Results There were 169 children randomized, with a mean (SD) age of 5 years 11 months (2 months); 91 (54%) were female. Of the participants, 84 were in the intervention group (57 of whom [68%] completed at least 15 cognitive training sessions) and 85 were in the control group. The posttraining visuospatial index score was not different between groups at a mean (SD) of 3.0 (1.8) months (difference, −0.6 points; 95% CI, −4.7 to 3.5 points) or 12.9 (2.6) months (difference, 0.1 points; 95% CI, −5.4 to 5.1 points). The working memory index score in the intervention group significantly improved from baseline at the intermediate time point (difference, 4.7 points; 95% CI, 1.2-8.1 points), but this improvement was not maintained at the final assessment. Conclusions and Relevance This randomized clinical trial found no lasting effect of a cognitive training program on visuospatial processing in children aged 5½ to 6 years with working memory disorders who were born very preterm. The findings suggest that this training has limited long-term benefits for improving executive function. Transient benefits seemed to be associated with the developmental state of executive functions. Trial Registration ClinicalTrials.gov Identifier: NCT02757794

Over the last few years, gambling has diversified, particularly with the arrival of legislation authorizing online gambling in 2010 in France. Psychology has been very interested in emotional regulation strategies, and more recently and more sparsely in the presence of shame and guilt. Through an observational study (N = 1955) shame, guilt, and emotional regulation were assessed among gamblers. We found that (i) Less guilt is associated with problem gambling, (ii) Shame-proneness is similar regardless of the type of gamblers, (iii) Every facet of emotion regulation indicates less effective strategies for problem gamblers excepted for a behavior oriented to a goal. These results suggest the importance of shame or guilt as predictors of problem gambling, as well as processes underlying emotion regulation.

Developing three-dimensional (3D) covalent organic frameworks (COFs) has paramount significance across numerous applications. However, the conventional design approach that relies on regular building blocks significantly restricts the structural diversity of COFs. In this study, we successfully designed and synthesized two 3D COFs, named JUC-643 and JUC-644, employing a novel strategy based on irregular 8-connected (8-c) building blocks. By using a continuous rotation electron diffraction technique combined with powder X-ray diffraction patterns, their structures were solved and revealed a unique linkage with double helical structure, a phenomenon previously unreported in COFs. In order to precisely describe the topology, these structures should be deconstructed into the unprecedented [4+3(+2)]-c nets instead of the traditional [8(+2)]-c or [6(+2)]-c net. Furthermore, one of the materials (JUC-644) has demonstrated exceptional adsorption capability towards C3H8 and n-C4H10 (11.28 and 10.45 mmol g-1 at 298 K and 1 bar respectively), surpassing the adsorption performance of all known porous materials, and breakthrough experiments have also highlighted the remarkable C3H8/C2H6 and n-C4H10/C2H6 selectivity. This pioneering concept of incorporating irregular building blocks in 3D COFs introduces a promising avenue for designing intricate architectures while enhancing their potential application in the recovery of C2H6 from natural gas liquids.