Search

Background/purpose: Post radiation mucosal ulcers (PRMU) after treatment for oropharyngeal squamous cell carcinoma (OPSCC) can have a huge negative impact on patients’ quality of life, but little is known concerning risk factors and the impact of fraction size. Therefore, the goal of this study was to determine the pattern of PRMU development and to identify risk factors after a hypofractionated stereotactic body radiotherapy boost (SBRT) compared to conventionally fractionated radiotherapy for OPSCC. Material and methods: We performed a retrospective cohort study (N = 332) of OPSCC patients with ≥ 1-year disease-free survival, treated with 46 Gy Intensity Modulated Radiotherapy (IMRT) (2 Gy fractions) followed by either an SBRT boost of 16.5 Gy (5.5 Gy fractions) (N = 180), or 24 Gy IMRT (2 Gy fractions) (N = 152). PRMU (grade ≥ 2) was scored when observed > three months after the last radiotherapy (RT) fraction (CTCAE v5.0). Potential risk factors were analyzed with Cox regression models using death as competing risk. Dose at the PRMU site was calculated by projecting delineated PRMU on the planning CT. Results: All cases of PRMU (N = 64) occurred within 24 months; all were grade 2. The cumulative incidence at 2 years in the SBRT boost group was 26% (N = 46) vs. 12% (N = 18) for conventional fractionation (p = 0.003). Most PRMU developed within nine months (N = 48). PRMU occurring > nine months (N = 16) were mainly observed in the SBRT boost group (N = 15). Sex (p = 0.048), acute tube feeding (p = < 0.001), tumor subsite tonsil (p = 0.001), and N stage (p = 0.017) were associated with PRMU risk at multivariable regression in the hypofractionated SBRT boost group. All 25 delineated PRMU were located within the high dose regions. Conclusion: The risk of PRMU should be included in the cost benefit analysis when considering future research using a hypofractionated SBRT boost for OPSCC patients.

BACKGROUND AND PURPOSE: Diversity, Equity and Inclusion (DEI) in the medical workforce is linked to improved patient care and innovation, as well as employee retention and engagement. The European Society for Radiotherapy and Oncology launched a survey to provide a benchmark of DEI and engagement among radiation oncology (RO) professionals in Europe.METHODS: An anonymous survey was disseminated among RO professionals in Europe. The survey collected demographics and professional information, and participants were asked if they felt they belonged to a minority group. A DEI and workforce engagement questionnaire by Person et al. evaluated 8 inclusion factors. A favourable score was calculated by adding the percentage of "strongly agreed" or "agreed" answers.RESULTS: A total of 812 complete responses were received from 35 European countries. 21% of respondents felt they belonged to a minority group, mostly based on race/ethnicity (5.9%), nationality (4.8%) and age (4.3%). Compared to benchmark data from the United States, scores were lower for most inclusion factors, and to a greater extent for minority groups. The overall favourable score was 58% for those belonging to a minority group, significantly lower than for other respondents (71%, pCONCLUSIONS: Our work indicates that actions to improve DEI and workforce engagement among RO professionals in Europe are urgently needed, in particular among minority groups. This would potentially improve employee wellbeing and retention, promoting high quality care and innovation.

Background and purpose: Quality of automatic contouring is generally assessed by comparison with manual delineations, but the effect of contour differences on the resulting dose distribution remains unknown. This study evaluated dosimetric differences between treatment plans optimized using various organ-at-risk (OAR) contouring methods. Materials and methods: OARs of twenty lung cancer patients were manually and automatically contoured, after which user-adjustments were made. For each contour set, an automated treatment plan was generated. The dosimetric effect of intra-observer contour variation and the influence of contour variations on treatment plan evaluation and generation were studied using dose-volume histogram (DVH)-parameters for thoracic OARs. Results: Dosimetric effect of intra-observer contour variability was highest for Heart Dmax (3.4 ± 6.8 Gy) and lowest for Lungs-GTV Dmean (0.3 ± 0.4 Gy). The effect of contour variation on treatment plan evaluation was highest for Heart Dmax (6.0 ± 13.4 Gy) and Esophagus Dmax (8.7 ± 17.2 Gy). Dose differences for the various treatment plans, evaluated on the reference (manual) contour, were on average below 1 Gy/1%. For Heart Dmean, higher dose differences were found for overlap with PTV (median 0.2 Gy, 95% 1.7 Gy) vs. no PTV overlap (median 0 Gy, 95% 0.5 Gy). For Dmax-parameters, largest dose difference was found between 0–1 cm distance to PTV (median 1.5 Gy, 95% 4.7 Gy). Conclusion: Dose differences arising from automatic contour variations were of the same magnitude or lower than intra-observer contour variability. For Heart Dmean, we recommend delineation errors to be corrected when the heart overlaps with the PTV. For Dmax-parameters, we recommend checking contours if the distance is close to PTV (

Highlights • Professional quality of life is crucial for oncology professionals. • Alexythymia and empathy affect the individual capacity to cope with stress. • Alexythimia has a negative impact on radiation therapists’ professional quality of life. • Higher empatic concern increases the quality of professional well-being. • This data may help targeting professionals at risk to implement preventive strategies., Background and purpose Physical and mental well-being are crucial for oncology professionals as they affect performance at work. Personality traits, as alexithymia and empathy, may influence professional quality of life. Alexithymia involves diminished skills in emotion processing and awareness. Empathy is pertinent to the ability to understand another’s ‘state of mind/emotion’. The PROject on Burn-Out in RadiatioN Oncology (PRO BONO) investigates professional quality of life amongst radiation oncology professionals, exploring the role of alexithymia and empathy. The present study reports on data pertinent to radiation therapists (RTTs). Material and methods An online survey targeted ESTRO members. Participants were asked to fill out 3 questionnaires for alexithymia, empathy and professional quality of life: (a) Toronto Alexithymia Scale (TAS-20); (b) Interpersonal Reactivity Index (IRI); (c) Professional Quality of Life Scale (ProQoL). The present analysis focuses on RTTS to evaluate compassion satisfaction (CS), secondary traumatic stress (STS) and Burnout and their correlation with alexithymia and empathy, using generalized linear modeling. Covariates found significant at univariate linear regression analysis were included in the multivariate linear regression model. Results A total of 399 RTTs completed all questionnaires. The final model for the burnout scale of ProQoL found, as significal predictors, the TAS-20 total score (β = 0.46, p

Highlights • 49% of 543 survey participants worked full-time from home during the COVID-19 pandemic. • Perceived productivity was lower, with associated feelings of guilt. • Anxiety and depressive symptoms were higher than normative values in Europe. • Anxiety symptoms were negatively correlated with the number of years in research. • Mental health symptoms were lower in participants with institutional health support., Introduction With the COVID-19 pandemic, individuals have been forced to follow strict social isolation guidelines. While crucial to control the pandemic, isolation might have a significant impact on productivity and mental health. Especially for researchers working in healthcare, the current situation is complex. We therefore carried out a survey amongst researchers in the field of radiation oncology to gain insights on the impact of social isolation and working from home and to guide future work. Materials and methods An online survey was conducted between March 27th and April 5th, 2020. The first part contained 14 questions intended to capture an overview of the specific aspects related to research while in isolation. The second (optional) part of the questionnaire was the validated Hospital Anxiety and Depression Scale (HADS), a self-reported measure used to assess levels of anxiety and depressive symptoms. Results From 543 survey participants, 48.8% reported to work full-time from home. The impact on perceived productivity, with 71.2% of participants feeling less productive, caused 58% of participants to feel some level of guilt. Compared to normative data, relatively high levels of anxiety and depressive symptoms were recorded for the 335 participants who filled out the HADS questionnaire. Group comparisons found the presence of a supportive institutional program as the sole factor of statistical significance in both anxiety and depressive symptom levels. People having to work full-time on location showed higher depressive symptom levels than those working from home. Anxiety scores were negatively correlated with the number of research years. Conclusion Results of the survey showed there is a non-negligible impact on both productivity and mental health. As the radiation oncology research community was forced to work from home during the COVID-19 pandemic, lessons can be learned to face future adverse situations but also to improve work-life balance in general.

Highlights • Burnout is critical for oncology professionals, affecting quality of life and performance at work. • Alexithymia and empathy are personality traits influencing the capacity to cope with stress. • Alexithymia increases burnout among medical physicists with a negative impact at work. • Higher level of empathy are correlated to a better professional quality of life. • This data may help identifying subjects at risk to implement preventive strategies., Background and purpose The professional quality of life of radiation oncology professionals can be influenced by different contributing factors, including personality traits. Alexithymia involves deficits in emotion processing and awareness. Empathy is the ability to understand another’s ‘state of mind/emotion’. We investigated professional quality of life, including burnout, in radiation oncology, exploring the role of alexithymia and empathy and targeting the population of medical physicists (MPs), since this professional category is usually underrepresented in surveys exploring professional well-being in radiation oncology and MPs may experience professional distress given the increasing complexity of multimodal cancer care. Material and methods An online survey was addressed to ESTRO members. Participants filled out three questionnaires to evaluate alexithymia, empathy and professional quality of life: a) Toronto Alexithymia Scale (TAS-20); b) Interpersonal Reactivity Index (IRI); c) Professional Quality of Life Scale (ProQoL). Professional quality of life as per ProQoL was considered as dependent variable. The three domains of the ProQoL, namely compassion satisfaction (CS), secondary traumatic stress (STS) and burnout were correlated with alexithymia (as per TAS-20) and empathy (as per IRI with three subcategories: empathic concern, perspective taking and personal distress) and demographic/professional characteristics as independent variables. Generalized linear modeling was used. Significant covariates on univariate linear regression analysis were included in the multivariate linear regression model. Results A total of 308 medical physicists completed all questionnaires. Alexithymia as per TAS-20 was correlated to decreased CS (β = −0.25, p

The possible uses of artificial intelligence (AI) in radiation oncology are diverse and wide ranging. Herein, the authors discuss the potential applications of AI at each step of the radiation oncology workflow, which might improve the efficiency and overall quality of radiation therapy for patients with cancer. The authors also describe the associated challenges and provide their perspective on how AI platforms might change the roles of radiation oncology medical professionals. Artificial intelligence (AI) has the potential to fundamentally alter the way medicine is practised. AI platforms excel in recognizing complex patterns in medical data and provide a quantitative, rather than purely qualitative, assessment of clinical conditions. Accordingly, AI could have particularly transformative applications in radiation oncology given the multifaceted and highly technical nature of this field of medicine with a heavy reliance on digital data processing and computer software. Indeed, AI has the potential to improve the accuracy, precision, efficiency and overall quality of radiation therapy for patients with cancer. In this Perspective, we first provide a general description of AI methods, followed by a high-level overview of the radiation therapy workflow with discussion of the implications that AI is likely to have on each step of this process. Finally, we describe the challenges associated with the clinical development and implementation of AI platforms in radiation oncology and provide our perspective on how these platforms might change the roles of radiotherapy medical professionals.

Coastal marine ecosystems, which play a crucial role in the biogeochemical and ecological functioning of the Earth, are highly sensitive to the combined effects of climate and human activities. Because of their location, coastal ecosystems are directly influenced by human activities, but it remains challenging to assess the spatial and temporal scales at which climate influences coastal ecosystems. We monitored 12 sampling stations, distributed in 8 ecosystems in France, over 2 decades for physico-biogeochemical parameters (temperature, salinity, concentrations of dissolved oxygen, nutrients and particulate material). The study encompasses a large diversity of temperate coastal ecosystems with respect to e.g. geomorphology, trophic status, tidal regime, river influence and turbidity. Time-series analysis coupled with standardised 3-mode principal component analyses, partial triadic analyses and correlations were used to assess bi-decadal variability and ecosystem trajectories, and to identify large-scale, regional and local drivers. Our results highlighted 2 abrupt changes in 2001 and 2005. The bi-decadal changes were related to changes in large-scale and regional climate, detected through proxies of temperature and atmospheric circulation, as well as through river discharge. Ecosystem trajectories tended to move towards an increase in temperature and salinity, and/or a decrease in chlorophyll a, nutrients and particulate matter. However, the magnitude of change, the year-to-year variability and the sensitivity to the 2001 and 2005 changes varied among the ecosystems. This study highlights the need for establishing long-term time series and combining data sets as well as undertaking multi-ecosystem and local studies to better understand the long-term variability of coastal ecosystems and its associated drivers.

Purpose: To optimize the diffusion-weighting b values and postprocessing pipeline for hybrid intravoxel incoherent motion diffusion kurtosis imaging in the head and neck region. Methods: Optimized diffusion-weighting b value sets ranging between 5 and 30 b values were constructed by optimizing the Cramér-Rao lower bound of the hybrid intravoxel incoherent motion diffusion kurtosis imaging model. With this model, the perfusion fraction, pseudodiffusion coefficient, diffusion coefficient, and kurtosis were estimated. Sixteen volunteers were scanned with a reference b value set and 3 repeats of the optimized sets, of which 1 with volunteers swallowing on purpose. The effects of (1) b value optimization and number of b values, (2) registration type (none vs. intervolume vs. intra- and intervolume registration), and (3) manual swallowing artifact rejection on the parameter precision were assessed. Results: The SD was higher in the reference set for perfusion fraction, diffusion coefficient, and kurtosis by a factor of 1.7, 1.5, and 2.3 compared to the optimized set, respectively. A smaller SD (factor 0.7) was seen in pseudodiffusion coefficient. The sets containing 15, 20, and 30 b values had comparable repeatability in all parameters, except pseudodiffusion coefficient, for which set size 30 was worse. Equal repeatability for the registration approaches was seen in all parameters of interest. Swallowing artifact rejection removed the bias when present. Conclusion: To achieve optimal hybrid intravoxel incoherent motion diffusion kurtosis imaging in the head and neck region, b value optimization and swallowing artifact image rejection are beneficial. The optimized set of 15 b values yielded the optimal protocol efficiency, with a precision comparable to larger b value sets and a 50% reduction in scan time.

Purpose or Objective A questionnaire among 543 radiation oncology (RO) professionals involved in research demonstrated that approximately half of them were forced to work full-time from home due to the COVID-19 pandemic (Dhont et al, ctRO, 2020). At the same time, those still working on location had to adjust to a new working environment. Both groups and especially early-career researchers experienced a substantial impact on mental health and work productivity. The aim of the current qualitative study was to assess in-depth the specific challenges faced by young researchers in RO and what constitutes helpful support in case of continuing or future adverse situations. Materials and Methods This study was conducted jointly by researchers in the field of RO and experts in qualitative research. Data was collected using online Focus Groups (oFGs) facilitated by qualitative research experts. Three oFGs were held with 7-11 young RO professionals (total N=25), in which data saturation was reached. Invitations to participate in the oFGs were sent out 30 days prior through the ESTRO newsletter, social media and personal networks. Inclusion criteria to participate were (1) working in RO, (2) in a European institution, and (3) with less than 10 years of research experience. Efforts were made to ensure a diverse panel. The design of the oFGs (Figure 1) comprised two main steps: (1) Deepening the understanding of experienced impacts during the COVID-19 pandemic, and (2) formulating solutions that could positively address the identified impacts. The oFGs were recorded and transcribed verbatim. Transcripts were analyzed via the qualitative analysis software Atlas (2019) through inductive coding. The coded segments were then translated into themes. $Φg Results In addition to years of research experience, seven other variables were identified as potentially impacting on the work or personal sphere in a positive and/or negative manner. In total ten main impacts were identified in the personal (2) and work sphere (8), which were either affected directly by the variables or indirectly through other impacts. It was for example found that job title could negatively impact the type of work the researcher had to perform during the pandemic, which in turn negatively impacted his/her mental health. All variables, impacts and how they relate are illustrated in Figure 2. Proposed solutions were mostly technical, illustrating that the most pressing issue was to ensure the possibility to perform one's work. Proposed solutions for social isolation (e.g. virtual social events) were often countered by the presence of “zoom fatigue”. $Φg Conclusion Different variables, their impacts and a complex interplay between them have been identified to determine how early-career RO professionals experienced working during the COVID-19 pandemic. Beyond technical solutions to enable remote working, the distinct personal situations must be considered when proposing solutions to support mental health in these situations.

How animals adapt their behavior according to regular time intervals between events is not well understood, especially when intervals last several seconds. One possibility is that animals use disembodied internal neuronal representations of time to decide when to initiate a given action at the end of an interval. However, animals rarely remain immobile during time intervals but tend to perform stereotyped behaviors, raising the possibility that motor routines improve timing accuracy. To test this possibility, we used a task in which rats, freely moving on a motorized treadmill, could obtain a reward if they approached it after a fixed interval. Most animals took advantage of the treadmill length and its moving direction to develop, by trial-and-error, the same motor routine whose execution resulted in the precise timing of their reward approaches. Noticeably, when proficient animals did not follow this routine, their temporal accuracy decreased. Then, naïve animals were trained in modified versions of the task designed to prevent the development of this routine. Compared to rats trained in the first protocol, these animals didn’t reach a comparable level of timing accuracy. Altogether, our results indicate that timing accuracy in rats is improved when the environment affords cues that animals can incorporate into motor routines.

Background and purpose: Different factors may influence the professional quality of life of oncology professionals. Among them, personality traits, as alexithymia and empathy, are underinvestigated. Alexithymia is about deficits in emotion processing and awareness. Empathy is the ability to understand another's 'state of mind'/emotion. The PROject on BurnOut in RadiatioN Oncology (PRO BONO) assesses professional quality of life, including burnout, in the field of radiation oncology and investigates alexithymia and empathy as contributing factors.Material and methods: An online survey was conducted amongst ESTRO members. Participants completed 3 validated questionnaires for alexithymia, empathy and professional quality of life: (a) Toronto Alexithymia Scale; (b) Interpersonal Reactivity Index; (c) Professional Quality of Life Scale. The present analysis, focusing on radiation/clinical oncologists, evaluates Compassion Satisfaction (CS), Secondary Traumatic Stress (STS) and Burnout and correlates them with alexithymia and empathy (empathic concern, perspective taking and personal distress) with generalized linear modeling. Significant covariates on univariate linear regression analysis were included in the multivariate linear regression model.Results: A total of 825 radiation oncologists completed all questionnaires. A higher level of alexithymia was associated to decreased CS (beta:-0.101; SE: 0.018; p Conclusions: Alexithymic personality trait increased burnout risk, with less professional satisfaction. Empathic concern was associated to increased stress, without leading to burnout, resulting in higher professional fulfillment. These results may be used to benchmark preventing strategies, such as work-hour restrictions, peer support, debriefing sessions, and leadership initiatives for professionals at risk. (c) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 147 (2020) 162-168

How animals time their movements to take advantage of behaviorally meaningful intervals is not well understood, especially in the supra-second timescale. It has been proposed that the appearance of a cue signaling the beginning of an interval triggers reproducible self-sustained dynamics across ensembles of neurons (an emergent population clock) which eventually lead to the execution of a well-timed behavioral response. Thus, after interval onset, motor timing should be largely independent of the exact structure of the environment or the presence of external noise (unpredictable variability in the environment). To test this hypothesis, we used a task in which rats could obtain a reward at the front of a motorized treadmill, if they approached it after a fixed time interval following trial initiation. Most animals took advantage of the treadmill length and its moving direction to develop, by trial-and-error, a unique motor routine whose execution resulted in the precise timing of their reward approaches. Noticeably, when proficient animals occasionally failed to follow this routine, the timing of their reward approaches was systematically poor. In a second step, we trained naive animals in modified versions of the task specifically designed to prevent the development of this motor strategy. Compared to rats trained in the first protocol, these animals never reached a comparable level of timing accuracy. Our results support the idea that well-timed behaviors emerge from the ability of animals to develop motor routines adapted to the structure of their environment. They also suggest that self-sustained neuronal activity alone may not be sufficient to support motor timing, at least in the supra-second timescale.

Resume Objectifs Les etudes epidemiologiques et fondamentales suggerent que les desordres lipidiques puissent etre impliques dans la physiopathologie de la gonarthrose. Les diverses etudes ayant evalue l’effet des statines ont montre des resultats contradictoires. Nous avons etudie l’effet des statines sur la progression radiologique chez des patients atteints d’une gonarthrose symptomatique confirmee sur les radiographies. Methodes 336 patients issus du groupe placebo de l’essai SEKOIA ont complete les 3 ans de suivi et ont ete inclus dans cette analyse post-hoc. La prise de statines etait evaluee lors de la visite d’inclusion. La mesure de l’interligne articulaire femorotibiale minimale etait effectuee sur des radiographies standards selon une methode automatisee a l’inclusion puis de facon annuelle. La progression radiologique etait definie comme un pincement ≥ 0,5 mm sur 3 ans. Resultats 71 patients etaient sous statines (21,1 %). Comparativement aux sujets non traites, ils avaient un BMI superieur (31,1 ± 5,3 vs. 29,3 ± 5,2 kg/m2, p = 0,008) et un plus grand nombre de facteurs metaboliques (≥ 3 facteurs : 43,7 % vs. 7,2 % ; pet 30 kg/m2) et des maladies cardiovasculaires [risque relatif 1,49 (IC95 % 1,10–2,02), pet = 0,010]. Conclusion Chez les patients ayant une gonarthrose symptomatique, l’utilisation de statines etait associee a une plus grande progression radiologique independamment des facteurs confondants (obesite, diabete de type 2, hypertension, duree de la maladie, intensite des symptomes et severite radiologique).

A Model Predictive Control (MPC) strategy based on the Evolutionary Algorithms (EA) is proposed for the optimal dispatch of renewable generation units and demand response in a grid-tied hybrid system. The generating system is based on the experimental setup installed in a Distributed Energy Resources Laboratory (LabDER), which includes an AC micro-grid with small scale PV/Wind/Biomass systems. Energy storage is by lead-acid batteries and an H2 system (electrolyzer, H2 cylinders and Fuel Cell). The energy demand is residential in nature, consisting of a base load plus others that can be disconnected or moved to other times of the day within a demand response program. Based on the experimental data from each of the LabDER renewable generation and storage systems, a micro-grid operating model was developed in MATLAB© to simulate energy flows and their interaction with the grid. The proposed optimization algorithm seeks the minimum hourly cost of the energy consumed by the demand and the maximum use of renewable resources, using the minimum computational resources. The simulation results of the experimental micro-grid are given with seasonal data and the benefits of using the algorithm are pointed out.

Objective Epidemiological and experimental studies have suggested that lipid disorders might be involved in the pathophysiology of knee osteoarthritis (OA). Studies assessing the effect of statins on knee OA progression have shown conflicting results. We investigated the impact of statin use on radiological progression in patients with radiological and symptomatic knee OA. Methods In total, 336 patients from the placebo arm of SEKOIA trial completed the 3-year follow-up and were included in this post-hoc analysis. Statin use was recorded at baseline interview. Minimal medial tibiofemoral joint space was measured on plain radiographs by an automated method at baseline and then annually. Radiologic progression was defined as joint space narrowing ≥ 0.5 mm over 3 years. Results Overall, 71 patients were statin users (21.1%). They had a higher BMI (31.1 ± 5.3 vs. 29.3 ± 5.2 kg/m2, P = 0.008), a higher sum of metabolic factors (≥ 3 factors: 43.7% vs 7.2%; P for trend < 0.001) and a higher rate of radiological progression (49.3% vs. 32.1%, P = 0.007) as compared to statin non-users. The significant association between radiological progression and statin use was independent of age, gender, WOMAC global score, disease duration, baseline joint space width, hypertension, type 2 diabetes, obesity (BMI > 30 kg/m2) and cardiovascular diseases [relative risk 1.49 (95% CI: 1.10–2.02), P = 0.010]. Conclusion Among patients with knee OA, statin use was associated with radiological worsening over 3 years, regardless of other potential confounding factors (obesity, type 2 diabetes, hypertension, disease duration, symptom intensity and radiological severity).

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

Funding: This meeting was founded by the European Society for Clinical and Economics Aspect of Osteoporosis and Osteoarthritis, a not for profit organization from Belgium. Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates. publishersversion published

22nd International Annual Congress of the World-Muscle-Society (WMS), Saint Malo, FRANCE, OCT 03-07, 2017; International audience

International audience; Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

The purpose of this study was to increase the potential of dose redistribution by incorporating estimates of oxygen heterogeneity within imaging voxels for optimal dose determination. Cellular oxygen tension (pO2) distributions were estimated for imaging-size-based voxels by solving oxygen diffusion-consumption equations around capillaries placed at random locations. The linear-quadratic model was used to determine cell survival in the voxels as a function of pO2 and dose. The dose distribution across the tumour was optimized to yield minimal survival after 30 × 2 Gy fractions by redistributing the dose based on differences in oxygen levels. Eppendorf data of a series of 69 tumours were used as a surrogate of what might be expected from oxygen imaging datasets. Dose optimizations were performed both taking into account cellular heterogeneity in oxygenation within voxels and assuming a homogeneous cellular distribution of oxygen. Our simulations show that dose redistribution based on derived cellular oxygen distributions within voxels result in dose distributions that require less total dose to obtain the same degree of cell kill as dose distributions that were optimized with a model that considered voxels as homogeneous with respect to oxygen. Moderately hypoxic tumours are expected to gain most from dose redistribution. Incorporating cellular-based distributions of radiosensitivity into dose-planning algorithms theoretically improves the potential gains from dose redistribution algorithms. © 2009 Institute of Physics and Engineering in Medicine.

Background:MicroRNA expression signatures can promote personalised care for non-small cell lung cancer (NSCLC) patients. Our aim was to evaluate the previously unexplored prognostic potential of miR-197, a key oncogenic molecule for NSCLC.Methods:Total RNA isolation (n=124 NSCLC and n=21 tumour-adjacent normal tissues), was performed using the QIAsymphony SP workstation. The quantity and quality of RNA were assessed by spectrophotometric analysis and an Agilent 2100 bioanalyzer. Polyadenylation and reverse transcription were subsequently carried out. MiR-197 expression levels were measured by qPCR, after quality control (inter-assay CV=7.8%). Internal validation procedures were followed by assigning training and test sets and robust biostatistical analyses were performed, including bootstrap resampling.Results:MiR-197 is associated with larger tumours (P=0.042) and the squamous cell carcinoma histotype (P=0.032). Interestingly, after adjusting for important prognostic indicators, miR-197 expression was identified as a novel independent predictor of unfavourable prognosis for NSCLC patients (HR=1.97, 95% CI=1.10-3.38, P=0.013). We also demonstrate that miR-197 retains its prognostic performance in both early-stage I (P=0.045) and more advanced-stage individuals (P=0.036).Conclusions:The cost-effective expression analysis of miR-197 could constitute a novel molecular tool for NSCLC management. © 2015 Cancer Research UK.

International audience; The 11th International Symposium on Aeromonas & Plesiomonas will be held on 25-27 June 2014 in Montpellier, France. By their niche diversity and their versatile behaviors, Aeromonas and Plesiomonas are fruitful models for advances in knowledge on bacterial adaptation. The conferences will cover all aspects of these microorganisms (molecular biology, phylogeny, evolution, taxonomy, ecology in water, human and animal, food, virulence factors, pathogenesis). The conferences are outstanding opportunities, occurring every 3years, for scientists from around the globe to come together to update on the latest knowledge, enjoy discussions with specialists in a Mediterranean environment. We hope to see you there!

The electric energy demand is dramatically growing worldwide and demand reduction emerges as an outstanding strategy; it implies detailed information about the electricity consumption, namely load disaggregation. Typical automatic methods for load disaggregation require high hardware efforts to install one sensor per appliance, whereas Non-intrusive Load Monitoring (NILM) systems diminish the hardware efforts through signal processing and mathematical modeling. One approach to NILM systems is to model the load signatures via artificial intelligence. This paper proposes to employ S-Transform for the feature extraction stage and Support Vector Machines for the pattern recognition problem. Several experiments are presented and the results of the feature extraction with S-Transform and Wavelet Packet Transform are compared. Thus promising feature vectors based on S-Transform are presented with similar or superior performance than the approach based on Wavelet Packet Transform.

Chez tous les ovipares, le foie est l'un des principaux organes cibles de l'oestradiol dont l'action est médiée par un récepteur spécifique, l'ER. Des études préliminaires ont montré, à la fois in vivo et en culture d'hépatocytes, que le gène du récepteur aux oestrogènes de truite arc-en-ciel Oncorhynchus mykiss (rtER) est régulé positivement par les oestrogènes. D'autres travaux ont également mis en évidence l'influence positive de facteurs de transcription tissus-spécifiques sur l'expression de ce gène. Au cours de ce travail, nous avons étudié l'unité transcriptionnelle constituée d'un fragment de 0,2 kb du promoteur rtER caractérisé au laboratoire, dans un organisme unicellulaire : la levure Saccharomyces cerevisiae. Nous avons montré que le rtER, lui-même, était capable d'activer ce promoteur. De plus, comme dans des cellules de mammifères, le facteur hCoup-TFI ("human-related Chicken Ovalbumin Upstream Promoter Transcription Factor I" est capable d'augmenter l'activation due au rtER. On a donc reconstitué, dans le système hétérologue de levure, une unité transcriptionnelle complexe qui pourrait constituer un modèle applicable à l'analyse de différents facteurs (métaux lourds, xénobiotiques, facteurs de transcription) intérférant avec l'autorégulation du gène rtER.

International audience; Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormalCAG repeat expansion coding for an expanded polyglutamine tract in the protein"huntingtin" (Htt). Although this mutant Htt (mHtt) is expressed ubiquitouslythroughout the brain, the striatum is found preferentially affected. One hypothesisto explain this particular vulnerability is that striatal neurons express a particularset of proteins that make them highly vulnerable to mHtt. In order to furtherexamine this hypothesis, we carried out a transcriptome analysis of different brainterritories and identified more than 100 molecular markers i.e. transcripts that arehighly enriched in the mouse striatum. We recently focused our interest on asubset of striatal-enriched transcripts of poorly characterized transcripts.We here report the study of one of these markers, the CAMKII family-relatedkinase DCLK3. We found that DCLK3 is mainly expressed in the adult striatum inrodent with low level of expression in the newborn and striatal primary cultures.Reduced mRNA levels of DCLK3 were found in the striatum of transgenic mousemodels of HD. We thus studied the effect of DCLK3 overexpression and knockdownin a mouse model of HD using lentiviral vectors coding for a N-terminalfragment of mHtt. DCLK3 and its related siRNA were delivered using lentiviralvectors. Striatal degeneration produced by mHtt was characterized usingimmunohistochemistry of DARPP32, Cytochrome oxidase and ubiquitin followedby quantitative histological evaluation. Results showed that lenti-siRNA targetingDCLK3 increased mHtt toxicity when compared to the control. On the contrary,overexpression of DCLK3 reduced the striatal lesions produced by mHtt in vivo.DCLK3 also decreased the number and size of ubiquitin-containing nuclearinclusions. Current experiments are examining the mechanisms that could underliethe neuroprotective effect of DCLK3 in striatal neurons. The present study suggests that DCLK3 is a potential modifier of the disease and might beconsidered in HD therapy to slow disease progression.

International audience; Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormalCAG repeat expansion coding for an expanded polyglutamine tract in the protein"huntingtin" (Htt). Although this mutant Htt (mHtt) is expressed ubiquitouslythroughout the brain, the striatum is found preferentially affected. One hypothesisto explain this particular vulnerability is that striatal neurons express a particularset of proteins that make them highly vulnerable to mHtt. In order to furtherexamine this hypothesis, we carried out a transcriptome analysis of different brainterritories and identified more than 100 molecular markers i.e. transcripts that arehighly enriched in the mouse striatum. We recently focused our interest on asubset of striatal-enriched transcripts of poorly characterized transcripts.We here report the study of one of these markers, the CAMKII family-relatedkinase DCLK3. We found that DCLK3 is mainly expressed in the adult striatum inrodent with low level of expression in the newborn and striatal primary cultures.Reduced mRNA levels of DCLK3 were found in the striatum of transgenic mousemodels of HD. We thus studied the effect of DCLK3 overexpression and knockdownin a mouse model of HD using lentiviral vectors coding for a N-terminalfragment of mHtt. DCLK3 and its related siRNA were delivered using lentiviralvectors. Striatal degeneration produced by mHtt was characterized usingimmunohistochemistry of DARPP32, Cytochrome oxidase and ubiquitin followedby quantitative histological evaluation. Results showed that lenti-siRNA targetingDCLK3 increased mHtt toxicity when compared to the control. On the contrary,overexpression of DCLK3 reduced the striatal lesions produced by mHtt in vivo.DCLK3 also decreased the number and size of ubiquitin-containing nuclearinclusions. Current experiments are examining the mechanisms that could underliethe neuroprotective effect of DCLK3 in striatal neurons. The present study suggests that DCLK3 is a potential modifier of the disease and might beconsidered in HD therapy to slow disease progression.

Magnetic and magnetostrictive hysteresis loops of TbCo/CoFe multilayers under field applied along the hard magnetization axis are studied using vectorial magnetization measurements, optical deflectometry and magneto optical Kerr microscopy. Even a very small angle misalignment between hard axis and magnetic field direction is shown to drastically change the shape of magnetization and magnetostrictive torsion hysteresis loops. Two kinds of magnetic domains are revealed during the magnetization: big regions with opposite rotation of spontaneous magnetization vector and spontaneous magnetic domains which appear in a narrow field interval and provide an inversion of this rotation. We show that the details of the hysteresis loops of our exchange-coupled films can be described using the classical model of homogeneous magnetization rotation of single uniaxial films and the configuration of observed domains. The understanding of these features is crucial for applications (for MEMS or microactuators) which benefit from the greatly enhanced sensitivity near the point of magnetic saturation at the transverse applied field., 10 pages, 11 figures

Exchange-coupled multilayered thin films which combine giant magnetostriction and soft magnetic properties are of growing interest for applications. TbFe 2 /Fe and TbFe 2 /FeCo nanometric multilayers were grown by RF-sputtering onto glass substrates. A bias field of 250 Oe was applied along the longitudinal axis, inducing an in-plane uniaxial magnetic anisotropy. For es-deposited multilayers, TbFe layers are amorphous while soft layers are nanocrystallized. The effect of annealing was investigated by 57 Fe Mossbauer spectrometry, magnetic and magnetostriction measurements in the temperature ( T ann ) range from 150 to 350 °C. After annealing, the Mossbauer analysis evidences for an increase of the crystallized iron component, probably due to a thinning of the interfaces. A maximum of the magnetoelastic coefficient is found for T ann around 250 °C, with the highest value obtained in the case of TbFe/FeCo. Furthermore, stress relaxation within the film reduces the anisotropy field, leading to a large magnetoelastic susceptibility of about 250 MPa/kOe.

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

A method is presented for the isolation of large quantities of myxoma virus DNA using pulsed-field gel electrophoresis (PFGE), and some preliminary applications of this technique.

The CPLEAR collaboration has constructed a detector at CERN for an extensive programme of CP-, T- and CPT-symmetry studies using K-0 and produced by the annihilation of in a hydrogen gas target. The K-0 and are identified by their companion products of the annihilation K(+/-)pi(-/+) which are tracked with multiwire proportional chambers, drift chambers and streamer tubes. Particle identification is carried out with a liquid Cherenkov detector for fast separation of pions and kaons and with scintillators which allow the measurement of time of flight and energy loss. Photons are measured with a lead/gas sampling electromagnetic calorimeter. The required antiproton annihilation modes are selected by fast online processors using the tracking chamber and particle identification information. All the detectors are mounted in a 0.44 T uniform field of an axial solenoid of diameter 2 m and length 3.6 m to form a magnetic spectrometer capable of full on-line reconstruction and selection of events. The design, operating parameters and performance of the subdetectors are described.