Université de Rennes 1

The notion of polyglot software development refers to the fact that most software projects nowadays rely on multiple languages to deal with widely different concerns, from core business concerns to user interface, security, and deployment concerns among many others. Many different wordings around this notion have been proposed in the literature, with little understanding of their differences. In this article, we propose a concise and unambiguous definition of polyglot software development including a conceptual model and its illustration on a well-known, open-source project. We further characterize the techniques used for the specification and operationalization of polyglot software development with a feature model, concentrating on polyglot programming. We conclude the article outlining the many challenges and perspectives raised by polyglot software development.

Diabetic nephropathy, also known as diabetic kidney disease (DKD), remains a challenge in clinical practice as this is the major cause of kidney failure worldwide. Clinical trials do not answer all the questions raised in clinical practice and real‐world evidence provides complementary insights from randomized controlled trials. Real‐life longitudinal data highlight the need for improved screening and management of diabetic nephropathy in primary care. Adherence to the recommended guidelines for comprehensive care appears to be suboptimal in clinical practice in patients with DKD. Barriers to the initiation of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors for patients with DKD persist in clinical practice, in particular for the elderly. Attainment of blood pressure targets often remains an issue. Initiation of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in routine clinical practice is associated with a reduced risk of albuminuria progression and a possible beneficial effect on kidney function. Real‐world evidence confirms a beneficial effect of SGLT2 inhibitors on the decline of glomerular filtration, even in the absence of albuminuria, with a lower risk of acute kidney injury events compared to GLP‐1RA use. In addition, SGLT2 inhibitors confer a lower risk of hyperkalaemia after initiation compared with dipeptidyl peptidase‐4 inhibitors in patients with DKD. Data from a large population indicate that diuretic treatment increases the risk of a significant decline in glomerular filtration rate in the first few weeks of treatment after SGLT2 inhibitor initiation. The perspective for a global approach targeting multifaceted criteria for diabetic individuals with DKD is emerging based on real‐world evidence but there is still a long way to go to achieve this goal.

Background Sepsis is a leading cause of death and serious illness that requires early recognition and therapeutic management to improve survival. The quick-SOFA score helps in its recognition, but its diagnostic performance is insufficient. To develop a score that can rapidly identify a community acquired septic situation at risk of clinical complications in patients consulting the emergency department (ED). Methods We conducted a monocentric, prospective cohort study in the emergency department of a university hospital between March 2016 and August 2018 (NCT03280992). All patients admitted to the emergency department for a suspicion of a community-acquired infection were included. Predictor variables of progression to septic shock or death within the first 90 days were selected using backward stepwise multivariable logistic regression to develop a clinical score. Receiver operating characteristic (ROC) curves were constructed to determine the discriminating power of the area under the curve (AUC). We also determined the threshold of our score that optimized the performance required for a sepsis-worsening score. We have compared our score with the NEWS-2 and qSOFA scores. Results Among the 21,826 patients admitted to the ED, 796 patients were suspected of having community-acquired infection and 461 met the sepsis criteria; therefore, these patients were included in the analysis. The median [interquartile range] age was 72 [54–84] years, 248 (54%) were males, and 244 (53%) had respiratory symptoms. The clinical score ranged from 0 to 90 and included 8 variables with an area under the ROC curve of 0.85 (confidence interval [CI] 95% 0.81–0.89). A cut-off of 26 yields a sensitivity of 88% (CI 95% 0.79–0.93), a specificity of 62% (CI 95% 57–67), and a negative predictive value of 95% (CI 95% 91–97). The area under the ROC curve for our score was 0.85 (95% CI, 0.81–0.89) versus 0.73 (95% CI, 0.68–0.78) for qSOFA and 0.66 (95% CI, 0.60–0.72) for NEWS-2. Conclusions Our study provides an accurate clinical score for identifying septic patients consulting the ED early at risk of worsening disease. This score could be implemented at admission.

Quantitative infarct estimation is crucial for diagnosis, treatment and prognosis in acute ischemic stroke (AIS) patients. As the early changes of ischemic tissue are subtle and easily confounded by normal brain tissue, it remains a very challenging task. However, existing methods often ignore or confuse the contribution of different types of anatomical asymmetry caused by intrinsic and pathological changes to segmentation. Further, inefficient domain knowledge utilization leads to mis-segmentation for AIS infarcts. Inspired by this idea, we propose a pathological asymmetry-guided progressive learning (PAPL) method for AIS infarct segmentation. PAPL mimics the step-by-step learning patterns observed in humans, including three progressive stages: knowledge preparation stage, formal learning stage, and examination improvement stage. First, knowledge preparation stage accumulates the preparatory domain knowledge of the infarct segmentation task, helping to learn domain-specific knowledge representations to enhance the discriminative ability for pathological asymmetries by constructed contrastive learning task. Then, formal learning stage efficiently performs end-to-end training guided by learned knowledge representations, in which the designed feature compensation module (FCM) can leverage the anatomy similarity between adjacent slices from the volumetric medical image to help aggregate rich anatomical context information. Finally, examination improvement stage encourages improving the infarct prediction from the previous stage, where the proposed perception refinement strategy (RPRS) further exploits the bilateral difference comparison to correct the mis-segmentation infarct regions by adaptively regional shrink and expansion. Extensive experiments on public and in-house NCCT datasets demonstrated the superiority of the proposed PAPL, which is promising to help better stroke evaluation and treatment.

Pathogenic bacteria employ complex systems to cope with metal ion shortage conditions and propagate in the host. IsrR is a regulatory RNA (sRNA) whose activity is decisive for optimum Staphylococcus aureus fitness upon iron starvation and for full virulence. IsrR down-regulates several genes encoding iron-containing enzymes to spare iron for essential processes. Here, we report that IsrR regulates the tricarboxylic acid (TCA) cycle by controlling aconitase (CitB), an iron-sulfur cluster-containing enzyme, and its transcriptional regulator, CcpE. This IsrR-dependent dual-regulatory mechanism provides an RNA-driven feedforward loop, underscoring the tight control required to prevent aconitase expression. Beyond its canonical enzymatic role, aconitase becomes an RNA-binding protein with regulatory activity in iron-deprived conditions, a feature that is conserved in S. aureus. Aconitase not only negatively regulates its own expression, but also impacts the enzymes involved in both its substrate supply and product utilization. This moonlighting activity concurrently upregulates pyruvate carboxylase expression, allowing it to compensate for the TCA cycle deficiency associated with iron scarcity. These results highlight the cascade of complex posttranscriptional regulations controlling S. aureus central metabolism in response to iron deficiency.

Although goniometric measurement is considered the gold standard for the measurement of digital range of motion, visual estimation is often employed due to its simplicity despite being inconsistent with recommended guidelines. We evaluated the Rennes Universal Measurement Method, an innovative tool employing artificial intelligence to concurrently analyse hand joint angles based on a single photograph. We found a strong correlation between the goniometric method and the photograph-based approach (Spearman correlation coefficient 0.7). The mean standard error of measurement was −1° (SD 17°). Regarding reproducibility with different photographic angles, an excellent intraclass correlation coefficient of 0.9 was noted. The tool had a processing time of less than 0.1 s per hand, while traditional goniometric methods took 20–30 s per finger. Combining simplicity, high reproducibility and good inter-rater reliability, this is a potentially useful tool that can be used to monitor patient progress in place of traditional goniometry.

Background The SEMAPHORE trial[1] was a randomized controlled prospective study to assess the safety and efficacy (success defined by PMR-AS≤10 and GC≤5mg or GC decrease ≥10mg/day) of intra venous (i.v.) tocilizumab (TCZ) in glucocorticoids (GC)-dependent polymyalgia rheumatica (PMR). Tocilizumab was shown to reduce GC while improving clinical and biological inflammatory parameters at 24 weeks. After the 24-week study, patients entered a double-blind extension. Objectives In this study, we aimed to assess after the 24th week the relapse rate and markers of patients who received a 6-month TCZ treatment and achieved remission. Methods Among 101 patients randomly 1:1 allocated to receive i.v. 8mg/kg TCZ or placebo for 24 weeks in the SEMAPHORE trial, 49 received TCZ and 33 of them succeed (Figure 1). All 33 patients but one stopped TCZ at week 24 and they visited at week 32, with optional follow-up visits every 8 weeks until week 48. The relapse was defined by the failure of the primary composite outcome during follow-up or the need for ≥1 TCZ infusion. Results are presented by proportion of patients achieving success at each visit and the outcome over time using a Kaplan Meier curve. Results Among the 33 TCZ group patients in remission at week 24, 7 stopped follow-up before the 48th week, 5 of the other 26 subjects (19.2%) sustained remission in the 6 following months, 21 (80.8%) relapsed. Median time to relapse was 15 weeks (interquartile range: 8-25). 15 patients were considered in relapse because of PMR-AS≥10, 4 for isolated CRP elevation, 2 after the clinician’s decision. Among the 16 patients treated with TCZ but not in remission at 24th week, 4 of them (25%) achieved the primary outcome after continuing TCZ for 24 other weeks. Conclusion Among patients with GC-dependent PMR, in remission after a 6-month TCZ treatment, only a quarter remained relapse-free after treatment discontinuation. This study suggests that a 6-month treatment is not enough to withdraw TCZ. Further studies assessing the required duration of anti-IL6-receptor treatment to limit PMR relapses are needed. REFERENCES [1] Devauchelle-Pensec, V. et al. Effect of tocilizumab on Disease Activity in patients with active polymyalgia rheumatica receiving glucocorticoid therapy: A Randomized Clinical Trial. JAMA 328 , 1053–1062 (2022). • Download figure • Open in new tab • Download powerpoint Figure 1. Flow chart of the patients included in the SEMAPHORE trial, orientation of patients after the 24th week • Download figure • Open in new tab • Download powerpoint Figure 2. Relapse-free survival among GC-dependant PMR patients in remission after a 6-month treatment of Tocilizumab Footnotes: Remission was defined by PMR-AS<10, and GC≤5mg/j or daily GC dose decreased by ≥10mg. Day 0 was the visit at 24th week in the SEMAPHORE trial Abbreviations: PMR: Polymyalgia rheumatica; PMR-AS: Polymyalgia rheumatica activity score Acknowledgements We thank the French rheumatologists, particularly those from the French University Hospital VICTOR HUGO (InnoVation en reCherche OsTeo-aRticulaire des Hôpitaux Universitaires du Grand Ouest) network (srouest.fr), and the general practitioners who referred their patients to this trial. We are grateful to the Clinical Investigations Center (CIC) 1412, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France, for centralizing the trial data and to Audrey le Goff, MS; Adrien Clarysse, MS; and Valentine Guiton, MS, of the Brest University Hospital research board (DRCI) at the Brest University Hospital, who received no compensation for their role in the study. Disclosure of Interests Baptiste Chevet Galapagos, I wrote congress review for a journal they own, I received support outside of this work from Amgen, Abbviie, Novartis, Santi, Sandoz, Souki Aghiles: None declared, Nowak Emmanuel Dr Nowak reported receiving nonfinancial support from Roche-Chugai Pharmaceutical, which donated the infusion form of tocilizumab during the conduct of the study., Dr Nowak reported receiving grants from the French National Program for Clinical Research, Guillermo Carvajal Alegria Dr Carvajal Alegria reported receiving personal fees from Chugai Pharmaceutical outside the submitted work., Emmanuelle Dernis Dr Dernis reported receiving personal fees from Novartis, Bristol Myers Squibb, UCB, AbbVie, Nordic Pharma, Amgen, and Janssen outside the submitted work., Christophe Richez Dr Richez reported receiving personal fees from Sanofi, personal fees from Lilly, and personal fees from Novartis outside the submitted work., Marie-Elise Truchetet: None declared, Daniel Wendling Dr Wendling reported personal fees from AbbVie, Bristol Myers Squibb, MSD, Pfizer, Chugai Pharmaceutical, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Eli Lilly, Grunenthal, and Galapagos outside the submitted work, Eric Toussirot: None declared, Aleth Perdriger: None declared, Jacques-Eric Gottenberg Dr Gottenberg reported receiving personal fees from Roche-Chugai Pharmaceutical, Sanofi, Pfizer, Eli Lilly, Gilead, and Abbvie and grants from Bristol Myers Squibb outside the submitted work., Renaud Felten: None declared, Bruno Fautrel Dr Fautrel reported receiving personal fees from Roche Chugai Pharmaceutical during the conduct of the study., Anne Lohse: None declared, Laurent Chiche: None declared, Pascal Hilliquin: None declared, Catherine Le Henaff Bourhis: None declared, Dervieux Benjamin: None declared, Guillaume Direz Dr Direz reported receiving personal fees from Novartis and personal fees from Roche-Chugai Pharmaceutical outside the submitted work., Isabelle Chary-Valckenaere: None declared, Divi Cornec: None declared, Dewi Guellec: None declared, Thierry Marhadour: None declared, Alain Saraux Dr Saraux reported receiving grants from Roche-Chugai Pharmaceutical and grants from the French National Program for Clinical Research during the conduct of the study and personal fees from Nordic Galapagos, AbbVie, Eli Lilly, Nordic, and Roche-Chugai and grants from Eli Lilly outside the submitted work., Valerie Devauchelle-Pensec Dr Devauchelle reported receiving personal fees from Chugai Pharmaceutical and AbbVie a, Dr Devauchelle-Pensec reported grants and personal fees from Novartis during the conduct of the study and personal fees from Galapagos, Pfizer, Bristol Myers Squibb, Janssen, and AbbVie outside the submitted work.

Introduction Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described. Method After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases. Results We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype–phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM , outside of the two previously known mutational hotspots. Conclusion Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.

Prior research on sustainability suggests that ambitious sustainability strategies are often turned into “business-as-usual” practices. Although ecological embeddedness—that is, actors’ physical and cognitive anchoring in their ecological environment—can help maintain sustainability ambitions, its collective dynamics and pluralistic moral foundations remain understudied. We rely on the economies of worth framework and the revelatory case of a biodynamic farm business experiencing sustained commercial growth to explore these blind spots by analyzing how ecological embeddedness was maintained despite this growth. We found that moral threats moved the organization away from its initial sustainability commitment and demonstrated how the farm maintained its ecological embeddedness through three mechanisms that involved multiple moral foundations: nurturing ecological inspiration, networking green projects, and unifying a green ethos. By inducing such mechanisms of moral recombination, our analysis advances sustainability studies by clarifying and bridging individual and collective dynamics of ecological embeddedness while revealing their multiple moral foundations; we also extend economies of worth research by demonstrating the role of ecological materiality in the alignment of organizations with the green world.

Background With the increasing demand for facial feminization surgery, there is a growing need for reliable and reproducible techniques to enhance outcomes. Objective This study aimed to evaluate the effectiveness of single-stage Naso-Orbito-Frontal (NOF) complex reshaping in facial feminization surgery. Effectiveness was gauged by CT scan assessments and an unvalidated patient satisfaction survey at 6 months post-operative. Methods The study included 155 transfeminine patients undergoing surgery of the upper third of the face. Outcomes were compared in patients receiving either Orbito-Frontal (OF) surgery or combined Naso-Orbito-Frontal (NOF) surgery. A comparative analysis of pre- and postoperative standardized CT scan sections was performed, focusing on multiple anatomic angles in two dimensions. A self-administered satisfaction questionnaire based on six FACE-Q items was completed at 6 months. Results Among the 155 patients, 65 underwent OF surgery, and 90 underwent NOF surgery. The follow-up period ranged from 6 to 36 months, with an average of 18 months. Significant changes in craniometric measurements were observed: in the OF group, average changes in nasofrontal, frontal tilt, and metopion angles were +12.3±0.2°, -8.5±2.2°, and +20.0±0.1° respectively (p<0.001); in the NOF group, same metrics were +28.5±0.3°, -9.3±2.4°, and +23.9±0.1° (p<0.001). The NOF group demonstrated higher overall satisfaction (Median: 4/5) compared to the OF group (Median: 3/5). No early complications were reported. Conclusion The NOF complex surgery is an effective approach in gender-affirming surgery of the upper third of the face, yielding predictable results and higher patient satisfaction. Level of Evidence 3.

In temperate regions, most insect species overwinter in diapause while others continue to be active, feed, and possibly reproduce despite adverse climatic conditions. For fruit flies which remain active winter long, the presence of winter-available fruit is crucial for population persistence. This study aimed to disentangle the relative effects of climatic, landscape, and local factors on infestation rates of an important winter trophic resource, mistletoe (Viscum album) fruit, by drosophilid flies. Mistletoe fruits were sampled between January and July 2022 in seven regions of France, across a wide range of climatic conditions from Mediterranean to temperate oceanic. The fruits were used both by the invasive Drosophila suzukii and by the native D. subobscura in the latter part of winter and throughout spring, suggesting that this resource may assist these species to overcome the winter bottleneck. Infestations by both flies were positively associated with the presence of fallen mistletoe fruit on the ground and semi-natural (forest, hedgerow) and anthropogenic (garden, park) habitats. The mistletoe’s host tree species also influenced the fruit infestation rate. Drosophila suzukii infestation rate was positively impacted by the accumulated thermal energy (‘degree days’) in the previous 14 days. Mistletoe could act as a catalyst for the development of spring D. suzukii generations and should be considered in the context of integrative pest management strategies to prevent early infestation of crop fruit. Graphical Abstract

In this chapter, K denotes a complete discrete valuation field of characteristic 0, with algebraically closed residue field k of characteristic p > 0, \( \mathcal{O}_k \) the valuation ring of K, \( \overline{\textit{K}} \) an algebraic closure of K

All rings considered in this book have an identity element; all ring homomorphisms map the identity element to the identity element. We mostly consider commutative rings, and rings are assumed to be commutative unless stated otherwise; in particular, when we take a ringed topos (X, A), the ring A is assumed to be commutative unless stated otherwise.

In this chapter, K denotes a complete discrete valuation field of characteristic 0, with algebraically closed residue field k of characteristic p > 0, \( \mathcal{O}_k \) the valuation ring of K, W the ring of Witt vectors with respect to p with coefficients in k

In this chapter, K denotes a complete discrete valuation field of characteristic 0, with perfect residue field k of characteristic p > 0, \( \mathcal{O}_k \) the valuation ring of K, W the ring of Witt vectors with respect to p and with coefficients in k

In this chapter, K denotes a complete discrete valuation field of characteristic 0, with algebraically closed residue field k of characteristic p > 0, \( \mathcal{O}_k \) the valuation ring of K, \( \overline{\textit{K}} \) an algebraic closure of K

Initiated by Faltings [18] and developed following different approaches including those by Tsuji and by the authors [3], the p-adic Simpson correspondence provides an equivalence of categories between certain p-adic étale local systems over an algebraic variety defined over a p-adic field and certain Higgs bundles. The key idea behind its construction comes from Faltings’ approach in p-adic Hodge theory, more precisely from his strategy for the computation of the cohomology of a p-adic etale local system.