Safran Cabin has announced the appointment of Frank Riom as Executive Vice President of Safran Cabin Services where he has brought valuable experience to various roles including as A380 Program Manager and A350 Program Manager Riom has also led the European services branch of Safran’s cabling division and website in this browser for the next time I comment By: Kristin Brooks Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced except with the prior written permission of Rodman Media This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Castignac, the French logistics platform owned by leading global alternative asset manager, Brookfield today announces the acquisition of three prime location assets in France 1,154,500 sqft off-market portfolio comprises a 588,258 sqft site in Riom a 406,941 sqft site in Vert-Saint-Denis and a 159,350 sqft site in Grenay The Riom site is leased while the other two sites are available to let These acquisitions take the Castignac portfolio to 30 assets and projects worth over €1 billion under management They follow the addition of warehouses in Paris Lyon and Orleans to the portfolio last year Castignac’s continued focus is on investment in strategically located supply chain facilities to meet tenant demand for Grade A assets with tactical transport links to major hubs in France and elsewhere in Europe The deal was brokered by Cushman & Wakefield with DLA Piper acting as lawyer and Etude NOTER as notary while ICPE and environmental due diligences were undertaken by Andine GROUP Julien Claude Bouilly, Managing Director, Head of Investments and Asset Management, Castignac, said: “This off-market portfolio acquisition concludes an exceptional investment year in 2024 for Castignac. This strengthens our strategic presence in Paris and Lyon, which are key logistics hubs in France We are pleased to expand our presence in these critical areas enabling us to better assist both existing and new tenants in strengthening their supply chains so they remain agile as markets continue to evolve.” French Robots-in-Ports Plan Receives Funding Boost Logistics Business © 2025 All Rights Reserved. | Privacy | Terms | Site Map Subscribe to our quarterly magazine and weekly newsletter to stay updated with the logistics industry By submitting this form you agree that the personal data you provided will be transferred to Logistics Business for processing in accordance with our Privacy Policy Tonight, we may see two worlds collide Is this the end of the large sales areas as we knew them? But would they really want to go? Ready, set, bet! On this occasion, we spoke with street artist Davide Vavalà China focuses on in transit shopping From Instagram sponsorship to million-dollar ads In Italy, there are figures embodying this vision, yet the fashion industry continues to overlook them The example of four emerging brands that challenge convention The brand new leather good from the French fashion house in the colours of Indian summer Following in the footsteps of Léna Situations, Mister V, Amixem and Andie Ella, Squeezie is now launching his new brand From Dubai to Brignoles, the revenge of a forgotten fruit From those for the pope's funeral to those for the inauguration of a government, to simple toasts The US President's attempt to save Hollywood passes, not surprisingly, through duties Which promises to reveal the whole truth about the rapper's famous “parties” Between bad experiences and a few too many statements about Anna Wintour And why it is important to constantly update your bio While in Italy university graduates are seeking their fortune abroad, US researchers are fleeing from Trump From May the 2nd to 4th Its two co-founders tell us why you should apply to it Interview with Samuel Ross Interview with Willy Chavarria Interview with Louis Gabriel Nouchi Interview with Mowalola Interview with Marni’s Francesco Risso Interview with Jean-Charles de Castelbajac Interview with Byredo’s Ben Gorham Interview with Ottolinger Interview with Massimo Giorgetti Beyond the traditional realms of fashion The eight finalists tell their stories A record year at the competition for young designers in Trieste The Chinese designer debuted at Milan Fashion Week with the support of Dolce&Gabbana Fashion might have forgotten the art of fantasy, but the Shanghai-based designer hasn’t Interview with Hillary Taymour, founder and creative director of Collina Strada The collab between Napapijri and PDF by Domenico Formichetti was the first chapter of a new way of making fashion Interview with the PROTOTYPES Duo Y2K satire by Shukri Lawrence and Omar Braika in collaboration with Barragàn The Danish brand that questions contemporary manufacturing When personalisation and durability come together in your virtual dressing room, and not only While the luxury sector seems to be in decline Hermès stands out with the opening of its 23rd leather workshop in France The luxurious Maison has recently completely renovated a former 7000m2 tobacco factory an industrial site listed as a historic monument This opening is part of the leatherworker's eco-responsible approach aiming to select local partner companies and to source and use sustainable materials for the renovation Hermès explained that it entrusted the Tracks-Architects firm with the renovation of these buildings giving them the mission to reconcile the group's real estate strategy's CSR ambitions with the spirit of the Maison The workshop employs 250 artisans who have been internally trained over the past few months in the unique skills of the independent luxury Maison The group relied on the expertise of teams from its other leather workshop in Auvergne located about twelve kilometers away and opened 20 years ago Hermès aims to preserve its artisanal excellence it opened the École Hermès des Savoir-Faire an apprentice training center accredited by the Ministry of National Education authorized to issue the Leatherworking Professional Aptitude Certificate and the Cutting Professional Qualification Certificate The core business of the luxury group, leather goods and saddlery, recorded a 15.7% increase in sales in the first half Hermès is increasing its production capacity opening on average one new leather workshop per year for the past ten years where recruitment and training are ongoing Get access to exclusive contents and keep yourself updated Get access to exclusive contents and keep yourself updated Select the topics in which you are interested: Every month a newsletter to receive updates from our creative media agency So you don't miss the chance to attend nss world events Every month the latest news from the French vertical of nss saw its first-half sales rise by 15.7% year-on-year to more than 3.2 billion euros Group sales for the period rose by 12% to €7.5 billion.To meet this growing demand Hermès has been increasing its production capacity at an average rate of one new leather goods production unit per year for the past ten years Username or E-mail Password Remember Me    Forgot Password Full access to this article is limited to International Leather Maker Subscribers Click Here to subscribe. 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Advertisement cookies are used to provide visitors with customized advertisements based on the pages you visited previously and to analyze the effectiveness of the ad campaigns. © Guillaume AmatA large exhibition hall This one opens very largely on the “Jardin de la Culture” This generous and continuous space is extended by a covered outdoor gallery perforated by the arches which is articulated around the conference room This plan’s organization manage viewers flows by proposing a quality path around the topic of the cinema’s world You'll now receive updates based on what you follow Personalize your stream and start following your favorite authors If you have done all of this and still can't find the email Tracks Architectes is an architectural firm founded in 2014 by architects Moïse Boucherie and Jeremy Griffon Their professional development is based on a frugal architectural approach which emphasizes the narrative and contextual aspects of a project Each proposal develops a story deeply rooted in its program and the revelation of a site's riches are themes of reflection that define the foundations of their projects Throughout their career they have received a series of awards and nominations such as those mentioned below: Mention at the 2018 First Work Prize for the "La colmena" nursery school in Perthes-en-Gâtinais (2018) Exhibition "La arquitectura manifesta" at ENSA Bretagne in Rennes (2018) Mention at the 2019 International Prize for Wood Architecture for the "La colmena" nursery school in Perthes-en-Gâtinais (2019) First Prize at the Île-de-France Wood Trophies 2019 for the "La colmena" nursery school in Perthes-en-Gâtinais (2019) Exhibition "Examples of Bois construction projects dedicated to construction" at ENSA Paris Belleville (2019) First National Prize for Construction Timber for the "La colmena" nursery school in Perthes-en-Gâtinais (2019) First Regional project award for wood construction in Ile-de-France (2023) First prize in the equipment category of the Grand Prix for terracotta tile architecture (2024) Archive Architecture Metrics details Radiation-induced oral mucositis (RIOM) is a prevalent oral complication that occurs in individuals undergoing radiotherapy or radiation treatment for head and neck tumors The presence of oral mucosal rupture and ulcerative lesions which are the defining features of this condition can significantly affect the quality of life of patients it can interfere with tumor therapy and contribute to an unfavorable prognosis Current evidence suggests that cellular inflammation and programmed cell death are important factors in disease development thalidomide (THD) has been revealed to reduce the incidence and severity of RIOM in patients undergoing chemoradiotherapy for nasopharyngeal carcinoma the mechanism through which THD improves RIOM remains unknown This study aimed to investigate the role of LZTS3 in RIOM by analyzing various sequencing datasets and conducting knockdown and overexpression experiments We used small interfering RNA transfection and LZTS3 overexpression followed by validation through polymerase chain reaction we identified LZTS3 as a potential target for THD regulation in RIOM we confirmed that LZTS3 has the ability to inhibit the inflammatory response and apoptosis of cells we also found that THD can regulate the expression of LZTS3 by upregulating thereby affecting inflammatory response and apoptosis We repeated these results in a live animal model THD has the potential to reduce the occurrence of oral mucositis in patients by upregulating LZTS3 levels These findings provide a promising avenue for future drug research and development to treat RIOM But LZTS3 has not been reported to play a role in the regulation of RIOM I conducted knockdown and overexpression experiments of LZTS3 in irradiated cell models and discussed the effects of THD and radiation on LZTS3 mouse models were developed to examine the protective mechanism of THD against RIOM with a specific focus on its effect on programmed cell death and immune system responses These findings hold potential for the identification of therapeutic targets for RIOM patients Established guidelines for animal experiments were adhered to in this study to ensure standard ARRIVE guidelines are followed The protocol of this study was consistent with those of the national studies and adhered to council recommendations for the treatment and utilization of animals in laboratory settings We acquired 4-week-old male C57BL/6J mice from the Animal Laboratory Center at Guangxi Medical University housing them in a specific pathogen-free environment we randomly assigned 25 mice to five groups Mice in the RT group were exposed to 16 Gy of radiation at a 600 Mu/min rate and were administered normal saline injections daily mice underwent the same radiation exposure mice underwent the same radiation exposure and THD treatment via a daily intraperitoneal injection of 40 mg/mL THD (dimethylsulfoxide [DMSO] dissolution; dose were injected with LZTS3 negative plasmid packaged with adeno-associated virus AAV1 and were treated with THD daily (intraperitoneal injection 40 mg/mL THD at a dose of 100 mg/kg) for 7 days were injected with LZTS3 plasmid packaged with adeno-associated virus AAV1 all mice with fully damaged tongues were collected for further analysis 12 days later All mice were killed by cervical dislocation We obtained and cultured human oral epithelial cell lines (HOEC 340217) in a humid environment at 37 °C with 5% CO2 using a complete medium for human oral epithelial cells (CM-H203 There was no mycoplasma infection during cell culture and the cells were transfected after two passes HOECs were transfected with the LZTS3 overexpression plasmid (oeLZTS3) small interfering RNA (siLZTS3) and small interfering RNA negative control (siNC) This process involved using Lipofectamine 6000 reagent (Thermo Fisher Scientific USA) following the manufacturer’s instruction and RT + Th + OE-LZTS3 groups were pre-treated with a 10 mg/mL THD solution (dissolved in DMSO) for 24 h the medium was replaced in preparation for further experiments and all the RT groups underwent radiotherapy with a 6 Gy dose for approximately 1.1 min After the harvested cells were washed twice in PBS they were added to 1 mL ice bath and pre-cooled in 70% ethanol followed by flow cytometry (CytoFLEX; BECKMAN COULTER) analyzed the cell cycle and used ModFit LT 5.0 to determine the proportion of cells in each sample at each stage Tongue tissues were fixed in 4% paraformaldehyde and then preserved in paraffin 3 μm sections were prepared and stained with H&E and Masson’s trichrome The CCK-8 cytotoxicity assay required seeding cells in a 96-well plate with a clear bottom at a density of 2 × 104 cell/ml The cells were treated according to the manufacturer’s instructions (BS350B and they were quantified using a multifunctional enzyme reader (FilterMax F3 the supernatant underwent homogenization and centrifugation at 4 ° C at 2000 rpm for 20 min and IL-1a levels according to the instructions provided with the kit The results were standardized to β-actin as an internal reference and protein expression levels were quantified using Image J Cellular damage was assessed using fluorescein isothiocyanate (FITC)-annexin V/propidium iodide (PI) staining Fluorescent signals were detected with FACScan (BECKMAN COULTER and FlowJo was used to analyze cellular apoptosis Early apoptotic cells were identified as annexin-V-FITC+/PI- late apoptotic cells as annexin-V-FITC+/PI+ The obtained mouse tongue tissues were preserved with formalin and fixed with paraffin wax The tissue was further cut to a thickness of 3 μm dewaxed to water and then antigen repaired followed by exposure to anti-rat LZTS3 antibodies (1:400) and stored at 4 °C for 12 h the slides were rinsed with PBS and exposed to biotinylated enzymic secondary antibody for 30 min The slides treated with streptavidin biotin HRP complex were further treated with DAB chromogenic agent and stained with hematoxylin Data are expressed using mean ± standard deviation from a minimum of three distinct experiments To assess the differences among various groups a one-way analysis of variance (ANOVA) was conducted The normality of the data distribution had been assessed before the parameter test was performed Data between groups were compared using a t-test Statistical analysis was conducted using SPSS v25.0 while charts were constructed using Prism v7.0 The outcome of the bilateral examination was considered statistically significant at a significance level < 0.05 (A) Cell activity was measured by MTT assay and the results showed the effect of different doses of X-ray irradiation on HOEC activity; (B) MTT assay was used to detect cell activity the results showed that thalidomide at 10μM concentration had the best recovery effect on cell activity; (C) ELISA results showed that thalidomide could effectively inhibit RIOM cell inflammatory factors; (D) The volcano map showed that the expression of differential genes increased in the RIOM cell model after the addition of thalidomide and the six genes with the most obvious upregulation and statistical significance were highlighted in red (Log2FC > 3 p < 0.01); (E) RT-qPCR results showed that the transcription level of IL-1β in RIOM cell models decreased significantly after overexpression of LZTS3; (F) ELISA results showed that the IL-1β Apoptosis-associated protein expression was assessed using western blotting (WB) Evaluation of OD value at 450 nm using CCK-8 assay following transfection Flow cytometry was used to determine the apoptosis ratios of HOECs after transfection (*p < 0.05 These results suggest that LZTS3 can protect cells from apoptosis LZTS3 enhances the production of inflammatory cytokines in HOECs ELISA was used to assess the protein expression levels of IL-1α (D) WB was used to detect protein expression levels associated with inflammation (G) including NF-κB p65 (H) and p-NF-κB p65 (I) THD decreased radiation-induced cell apoptosis Apoptosis-associated protein expression was assessed using western blotting (WB) (D) Evaluation of OD value at 450 nm using CCK-8 assay following transfection (K) Flow cytometry (L) was used to measure the apoptosis ratios of HOECs after transfection (n = 3 Between different groups after radiotherapy apoptosis rate and the introduction of THD relationship (J) WB analysis (G) was performed to determine protein expression levels associated with inflammation specifically of NF-κB p65 (H) and p-NF-κB p65 (I) THD inhibits apoptosis by downregulating LZTS3 in irradiated mice (A) Immunohistochemical staining of LZTS3; (B) Statistical diagram of staining intensity of LZTS3; H&E staining (C) and Masson staining (D) of the tongue tissue and caspase-9 (M) was analyzed using western blotting (E) THD reduces inflammation in irradiated mice specifically NF-κB p65 (H) and p-NF-κB p65 (I) Researchers have long strived for the safety and effective control of RIOM no reports on LZTS3 involvement in RIOM exist reveal that LZTS3 can inhibit apoptosis and pro-inflammatory cytokine secretion in RIOM this study elucidated the mechanism by which THD can effectively treat RIOM by evaluating LZTS3 levels thereby providing further support for its clinical utilization LZTS3 was observed to inhibit pro-inflammatory molecule secretion LZTS3 could influence apoptosis by affecting Bax To inhibit the radiation-induced downregulation of LZTS3 THD up-regulate LZTS3 expression at the transcriptional and protein levels consequently mitigating apoptosis and pro-inflammatory factor release as THD effectively inhibited apoptosis and inflammation by upregulating LZTS3 expression in an irradiated mouse model our sequencing data originated from processed cell lines RIOM pathogenesis differs significantly across various stages making it uncertain at which stage THD contributes We should further explore the combined application of thalidomide with other therapeutic methods such as immunotherapy and further verify the difference in efficacy through experimental data this study identified the downstream acting factor LZTS3 that THD plays a therapeutic role in RIOM LZTS3 can inhibit cell apoptosis and the release of inflammatory factors and THD plays a protective role by up-regulating LZTS3 This lays a solid foundation for the medical application of THD and provides a potential target for the future treatment of RIOM Data will be availability on reasonable request The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies Evaluation of radiation-induced oral mucositis by optical coherence tomography Clin cancer Research: Official J Am Association Cancer Res and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies Adjunctive treatments for the prevention of chemotherapy- and radiotherapy-induced mucositis Oral mucositis: an update on innate immunity and new interventional targets Oral mucositis induced by anticancer therapies Oral mucositis complicating chemotherapy and/or radiotherapy: options for prevention and treatment Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity Chemotherapy- and radiotherapy-induced oral mucositis: pathobiology SADJ: J South Afr Dent Association = Tydskrif Van die Suid-Afrikaanse Tandheelkundige Vereniging Thalidomide ameliorates rosacea-like skin inflammation and suppresses NF-κB activation in keratinocytes Thalidomide represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling Thalidomide use in the management of oromucosal disease: a 10-year review of safety and efficacy in 12 patients Modulation of radiation-induced oral mucositis by thalidomide: preclinical studies Strahlentherapie Und Onkologie : Organ Der Deutschen Rontgengesellschaft Efficacy and safety of thalidomide in preventing oral mucositis in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: a multicenter Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Normal tissue complication probability (NTCP) modelling of severe acute mucositis using a novel oral mucosal surface organ at risk Clinical oncology (Royal College of Radiologists (Great Britain)) Systematic review of normal tissue complication models relevant to standard fractionation radiation therapy of the head and neck region published after the QUANTEC reports MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy double-blind trial of GC4419 versus placebo to reduce severe oral mucositis due to concurrent radiotherapy and cisplatin for head and neck cancer J Clin Oncology: Official J Am Soc Clin Oncol Long non-coding RNA (lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating leucine zipper tumor suppressor (LZTS3) through sponging microRNA miR-1275 LZTS3/TAGLN suppresses cancer progression in human colorectal adenocarcinoma through regulating cell proliferation Integrative gene expression profiling analysis to investigate potential prognostic biomarkers for colorectal cancer Med Sci Monitor: Int Med J Experimental Clin Res Download references This study was supported by grants from the National Natural Science Foundation of China (82260627and 82260604) Mei Gan and Huanshuo Miao contributed equally to this work The Sixth Affiliated Hospital of Guangxi Medical University Cancer Hospital of Dalian University of Technology Cancer Hospital of China Medical University he Sixth Affiliated Hospital of Guangxi Medical University The First Affiliated Hospital of Gannan Medical University provided insightful suggestions and experimental materials All authors read and approved the final manuscript I promise that the study was performed according to the international national and institutional rules considering animal experiments The study protocol was approved by the Guangxi Medical University The authors declare that they have no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Below is the link to the electronic supplementary material Download citation DOI: https://doi.org/10.1186/s12967-024-05648-z Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. 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Read more about them in our Privacy Policy View all Topics View all Explainers As governments worldwide are increasing their commitments to tackling climate change efforts are growing to quantify and characterise the ‘green economy’ and to identify opportunities to be seized and challenges to be overcome in the transition to the net-zero economy of the future The aim of this report and accompanying policy brief is to shed light on the quantity and quality of current green labour markets to inform policy action and future research for the net-zero transition The authors apply an occupation-level classification of ‘green jobs’ developed by O*NET in the United States The O*NET database distinguishes three occupational categories that differ regarding the effect of the transition to a climate-neutral and sustainable economy on occupations Figure 1 illustrates the ‘greenness’ of these three categories The narrowest definition of a green job would focus on the new and emerging category but these can be considered ‘directly green’ since they involve explicitly green tasks as defined by O*NET Increased demand jobs are a broader concept and are considered ‘indirectly green’ Report produced with the Centre for Economic Performance and the Programme on Innovation and Diffusion (POID) Dr Anna Valero is a Senior Policy Fellow at the Centre for Economic Performance and the Deputy Director of the Programme on Innovation and Diffusion (POID) Jiaqi Li is a Research Assistant for Anna Valero and a MRes/PhD student at Warwick University Sabrina Muller is a Sustainable Finance Policy Analyst at the Grantham Research Institute Capucine Riom is a PhD candidate in Economic Geography at LSE and a Research Assistant for the Grantham Research Institute and the What Works Centre for Local Economic Growth Dr Viet Nguyen-Tien is a Research Economist at the Centre for Economic Performance Mirko Draca is a Professor at Warwick University Director of the Centre for Competitive Advantage in the Global Economy (CAGE) and a Research Associate at the Centre for Economic Performance Former Policy Analyst - Sustainable Finance Sign up to our newsletter Further contact details and map Volume 7 - 2017 | https://doi.org/10.3389/fonc.2017.00089 Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients It is a normal tissue injury caused by radiation/radiotherapy (RT) which has marked adverse effects on patient quality of life and cancer therapy continuity It is a challenge for radiation oncologists since it leads to cancer therapy interruption RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer patients its economic cost was estimated to reach 17,000.00 USD per patient with head and neck cancers Figure 1. Pathobiology of oral mucositis (OM) (10) Sonis has suggested five stages (phases) of OM injury induced by radiotherapy (RT) and/or chemotherapy (CT): initiation The pathogenesis of each phase is illustrated Radiation-induced oral mucositis occurs in up to 80% of head and neck cancer irradiated patients and reaches up to 100% in patients with altered fractionation head and neck cancer. RIOM of grade 3 and 4 have been recorded in 56% of head and neck cancer patients treated with radiotherapy (1, 12) Many risk factors have been identified for RIOM. These risk factors include concomitant chemotherapy (CT), bad oral hygiene, below average nutritional stratus, lack of antibiotic use at early stage mucositis, and smoking (13) Table 1. Data analysis for RIOM predictors using IBM SPSS version 21.0 (Armonk, NY, USA) (14) Table 2. Patient-linked factors leading to increased risk for oral mucositis (OM) (15) Radiation-induced oral mucositis side effects and sequels include oral pain in 69% of patients, dysphagia in 56% of patients, opioid use in 53% of patients, weight loss of 3–7 kg, feeding tube insertion and hospitalization (ICU admission) in 15% of patients, and modification or interruption of treatment in 11–16% of patients (1, 12, 16) In the United States, RIOM may add up to 1,700.00–6,000.00 USD per patient depending on the inflammatory grade of the injury (12). RIOM treatment adds an economic cost that was estimated to increase up to 17,000.00 USD per patient treated for head and neck cancers (16) The pathophysiology of RIOM is not fully understood. Recent studies proposed that the pathogenesis of RIOM is composed of four phases: an initial inflammatory/vascular phase, an epithelial phase, a (pseudomembranous) ulcerative/bacteriological phase, and a healing phase (2, 5) The epithelial phase is initiated within a week by the apoptotic and cytotoxic effects of RT on the proliferating basal cells. This is why the recovery period is dependent on the rate of epithelial turnover, which could be enhanced by growth factors like epidermal growth factor and keratinocyte growth factor (KGF) (19) Table 3. Signaling pathways involved in the development of mucositis (10) In 2004, Sonis suggested five stages (phases) of OM injury induced by radiotherapy (RT) and/or CT: initiation, signaling, amplification, ulceration, and healing (Figure 1) (16) Figure 2. Redding’s summary of RT and/or chemotherapy (CT)-induced oral mucositis pathobiology (11) Redding has summarized the pathobiology phases of radiation-induced oral mucositis induced by RT and/or CT initiation phase with RT and/or CT results in direct and lethal DNA damage which leads to release of reactive oxygen species (ROS) from epithelial and tissue macrophages with cycles of amplifications the DNA damage and ROS lead to three major steps: (1) fibronectin breakdown that activates macrophages ending with stimulation of matrix metalloproteinase; (2) nuclear factor-κB (NF-κB) activation that stimulates the gene expression and release of pro-inflammatory cytokines and IL-6; and (3) ceramide pathway through sphingomyelinase and ceramide synthase The result will be more tissue injury and stimulated apoptosis there is restimulation of tissue damage and apoptosis by the major pro-inflammatory cytokines (TNF-α During the ulceration and loss of the protective barrier secondary infection adds more pro-inflammatory reactions and complicates the already existing inflammation before the healing phase starts by matrix signaling to basal epithelial cells to migrate Figure 3. Signal amplification during OM induced by RT and/or CT (10) Signal amplification during RT- and/or CT-induced OM is mediated by activation of NF-κB that is reactivated by IL-1β NF-κB induces the expression of genes responsible for the MAPK and tyrosine kinase pathways to finally activate the MMP1 and MMP3 signaling at the injured tissue cells tumor necrosis factor-α; IL-1β There has been more than one grading scale for RIOM. Table 4 shows the comparison of different RIOM scoring scales (14, 21–23) Table 4. Comparison of OM scoring scales (14, 21–23) World Health Organization Oral Toxicity Scale measures the anatomical, symptomatic, and functional elements of OM (Figure 4). The Radiation Therapy Oncology Group (RTOG) determined the acute radiation morbidity scoring criteria for mucous membranes. Finally, the Western Consortium for Cancer Nursing Research describes only the anatomical changes associated with OM (24) World Health Organization’s Oral Toxicity Scale Table 5. Toxicity grading of oral mucositis (OM) according to World Health Organization (WHO) and National Cancer Institute Common Toxicity Criteria (NCI-CTC) criteria (2)a The OM Index (OMI) scores the severity of OM by the erythema, ulceration, atrophy, and edema (a scale of 0–3 was designated for each element: 0 = none and 3 = severe). The OMI is considered internally consistent with high test–retest and interscorer reliability, and it shows solid validity (27) All these scoring scales are validated and are required in assessing RIOM and the therapeutic benefits of any new treatment of RIOM Table 6. Oral assessment guide (30) Because similar conditions can coexist in immunocompromised patients including cancer patients receiving RT and/or CT, differential diagnosis for RIOM is critical. Table 7 shows possible similar conditions (Figure 5) (20, 31) Table 7. Differential diagnosis of RIOM (20, 31) Differential diagnosis of radiation-induced oral mucositis The general long-term prognosis is reasonably good since most lesions resolve within 2–4 weeks after stopping the RT or CT. Although RIOM is considered a self-limited injury in some patients, it could be a lethal injury in moderately to severely ill patients, which could lead to ICU admission with obligatory cessation of RT. Patient losses are a common event under these circumstances (32) Maintaining good oral care is the main preventive measure for RIOM to minimize the risk for candidiasis or secondary bacterial infection, especially in hyperfractionated radiotherapy, combined CCRT regimens, or RT combined with a targeted agent due to increased mucositis severity (3) We will summarize the most recent agents and measures to prevent RIOM The good oral care can be summarized as follows: – Rinsing with a non-irritating solution – Daily ultrasoft tooth brushing with fluoride toothpaste – Very soft diet with low sugar and non-acidic food and drinks (Table 8) – Flossing is not recommended due to low platelet count – Other preventive procedures include minimizing the microbial load (will be discussed more in the treatment section) and educating the patient on good oral hygiene 2. Cryotherapy has been recommended for CT-induced OM, but no proven role in RIOM due to insufficient evidence (33) 5. Radiation shields (intraoral devices), midline mucosa-sparing blocks, 3-D and RT field design, intensity-modulated radiation therapy (IMRT), and removal of separable prosthetics are shown in preclinical studies to reduce the radiation scatter and the RIOM injury (66–69) 6. Low-energy helium–neon laser applied before RT showed significant reduction in the duration and the severity of RIOM in head and neck cancer patients (70). MASCC/ISOO guidelines suggest the use of low-level laser therapy in CT-induced OM at centers that can provide the necessary technology and training (33) Table 8. Diet recommended for RIOM patients (20) Table 9. Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for oral mucositis (3) No single agent has been approved by the US-FDA for the treatment of RIOM. Symptoms reduction and complications prevention of RIOM, including nutritional support, pain control, prophylaxis, and/or treatment of secondary infections, are considered the main cornerstone in the management of RIOM (34–36) Agents that were investigated and/or applied in RIOM treatment are discussed in the context of recently updated evidence-based preclinical and clinical studies 1. Glycyrrhetinic acid/povidone/sodium hyaluronate gel has mechanical action implemented in the relief of pain in RIOM. It adheres to the mucosal surface of the mouth, soothing oral lesions. Nevertheless, the preclinical studies are controversial, and only one clinical trial on unknown results was conducted to date (71) 2. l-Glutamine is a non-essential amino acid that counteracts RT-induced metabolic deficiencies (72). Locally applied l-glutamine reduced the RIOM in a randomized clinical trial (73). Glutamine powder for oral suspension was approved by the US-FDA for topical application in management of CT-induced OM, mainly IOMyet (74) 3. Manganese superoxide dismutase is a detoxifying agent that removes ROS. It was shown to have radioprotective effects against RT-induced colitis, esophagitis, hepatic cells apoptosis, and intestinal and eye injury (75–98) Phase I dose escalation study of GC4419 (manganese-containing macrocyclic ligand complex similar to naturally occurring superoxide dismutase enzymes) in combination with CT/RT for squamous cell cancer of the head and neck has just been completed waiting for results release (NCT01921426) 5. The application of corticosteroids mouthwashes has shown promising results. The limited availability of a large-scale data is a gap that should be bridged through relevant clinical studies (109) 6. Allopurinol and uridine were shown to be effective in reducing 5-fluorouracil oral toxicity in preclinical studies (110–114). Despite these results, they were ineffective approaches in randomized clinical trials as a therapy to reduce the treatment-related oral toxicity (115, 116) 8. Artificial saliva spray is an over-the-counter agent frequently used to alleviate mucosal dryness in mild cases of RIOM (121) 9. Chamomile has anti-inflammatory, antipeptic, antispasmodic, and antibacterial effects. It was investigated with encouraging results as an emulsion therapy for CT-induced mucositis (122–126) Studies are needed for its application in RIOM to determine its efficacy 10. Honey has been investigated in many preclinical studies due to its mucosal protective effect that was confirmed as a reduction in the incidence and severity of RIOM (127–132). However, the available clinical trial used only Manuka honey, and it appears to contradict the preclinical studies’ results (133) More studies are needed to confirm the therapeutic potential of honey in RIOM 12. Vitamin A and its derivatives have anti-inflammatory and epithelial proliferative effect (152). Topical tretinoin has been shown to reduce the oral complications during bone marrow (BM) transplantation (153) 13. Vitamin-E (tocopherol) has been shown to lower the oxidative damage of the oral mucosa and reduce the incidence of symptomatic RIOM in head and neck cancer patients in a randomized double-blind clinical trial (152, 154) 14. Sodium alginate was shown to reduce the discomfort and the severity of RIOM in a randomized clinical trial (155) 16. Povidone-iodine is an antiviral, antibacterial, and antifungal agent. Randomized clinical study showed that povidone-iodine reduces the incidence, severity, and duration of CCRT-induced OM, in addition to its advantages of being cheap and easily applied (118, 158–160) 17. Capsaicin is an inhibitor of neutrophils that reduces the pain sensation. One clinical trial showed that orally applied capsaicin caused temporary relief of pain in mucositis caused by RT and CT (161) more studies are needed for optimization of its analgesic effect Systemic GM-CSF therapeutic potential is still controversial and requires further investigation 4. Transforming growth factor-β3 inhibits the oral basal cell proliferation. It was shown to reduce the incidence of CT-induced mucositis (194) a reliable clinical trial is needed to assess its therapeutic potential with RT 5. Beta-carotene’s antioxidative effect (195, 196) was implemented in a randomized clinical trial where there was a significant reduction in the incidence of severe OM in CCRT (197) 6. Analgesics are strong candidates for alleviating the pain related to RIOM. A retrospective study showed that opioid therapy remains a corner stone for OM pain management in CCRT, as suggested by the MASCC/ISOO guidelines (33, 198) 7. Azelastine is a potent second-generation selective histamine antagonist that is used as an anti-inflammatory and antioxidant agent. One clinical trial showed significant reduction in the incidence and the severity of OM with CCRT (199) 8. Propantheline is an anticholinergic agent that reduces the salivary flow. One clinical trial showed that propantheline and oral cryotherapy may be feasible and effective in reducing mucosal toxicity in cancer patients receiving high-dose CT (200) 9. Immunoglobulins have lower salivary and systemic levels in patient receiving antineoplastic therapy. They have immune-modulating and anti-inflammatory properties. Intravenous or intramuscular immunoglobulins are frequently applied as prophylactic and therapeutic options for RIOM (158, 201) 10. Systemic corticosteroids were used in RIOM management. A double-blind placebo-controlled randomized trial has shown a tendency toward reduced RT interruption in prednisone-treated relative to placebo-treated patient groups without evidence of reduced RIOM incidence or severity (202) 11. Pentoxifylline regulates endotoxin-induced production of TNF-α. Although the preclinical studies showed significant reduction in the severity of RIOM with pentoxifylline (203), the clinical trials show that it is not effective in reducing the antineoplastic oral toxicity (204–208) 12. Salicylic acid derivatives should be avoided due to the increased risk for bleeding (34–36) 13. Sphingomyelinase and ceramide synthase inhibitors can be a potential candidate for RIOM. They inhibit the ceramide pathway-mediated RT-induced apoptosis (209–216) No current clinical trials have been started for them yet There is a current phase II clinical trial to evaluate the safety and efficacy of brilacidin oral rinse in patients with head and neck cancer (NCT02324335) Table 10. Radiation-induced oral mucositis (RIOM) the clinical trials that have been done until 2001 (2)a Table 10 summarizes the clinical trials that were done until 2001 for prevention (P) and treatment (T) of RIOM (2). The current clinical trials for RIOM are summarized in Table 11 and were found when searching the clinical trials website of the National Institute of Health for RIOM We have documented 40 RIOM treatment and prevention clinical trials Table 11. Clinical trials for RIOM as listed on http://www.ClinicalTrials.gov when searched in November 2015 RIOM is a self-limited radiotherapy-induced normal tissue injury It is a dose-limiting toxicity in most cases of head and neck cancer patients Many preclinical and clinical studies have been conducted for the prevention and treatment of RIOM there are numerous prevention and treatment strategies for RIOM there is no single agent or management regimen that has been agreed upon between caregivers that significantly improves RIOM to a clinically relevant and satisfactory standard the current guidelines recommend good oral care RIOM treatment focuses on palliative measures and symptoms relief; e.g. mesenchymal stromal cells therapy for RIOM shows promise for potential therapeutic and clinically relevant benefits more studies are still needed to confirm such therapeutic potential The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest OM is an awardee of the Lady Davis Institute/Toronto-Dominion Bank studentship This study was supported partially by Ride To Conquer Cancer (RTCC Jewish General Hospital Foundation) and Fonds de Recherche du Quebec-Santé (FRQS) grants English language editing was done by Jenny Warrington Clin Cancer Res (2005) 11(14):5121–7 CA Cancer J Clin (2001) 51(5):290–315 Curr Oral Health Rep (2015) 2:202–11 Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis – are there new strategies Bone Marrow Transplant (1999) 24(10):1095–108 Chemotherapy-induced and/or radiation therapy-induced oral mucositis—complicating the treatment of cancer [Current approaches in prevention and therapy of chemo- and radiotherapy-induced oral mucositis] Wien Med Wochenschr (2001) 151(3–4):53–65 Radiation therapy and chemotherapy-induced oral mucositis Braz J Otorhinolaryngol (2007) 73(4):562–8 Pathobiology of oral mucositis: novel insights and opportunities Google Scholar PubMed Abstract | Google Scholar Int J Radiat Oncol Biol Phys (2007) 68(4):1110–20 [Analysis of oral mucositis risk factors during radiotherapy for nasopharyngeal carcinoma patients and establishment of a discriminant model] Changes and predictors of radiation-induced oral mucositis in patients with oral cavity cancer during active treatment Eur J Oncol Nurs (2015) 19(3):214–9 Prevention and management of oral mucositis in patients with cancer CrossRef Full Text | Google Scholar biology and therapeutic opportunities of oral mucositis Perspectives on cancer therapy-induced mucosal injury Cancer (2004) 100(9 Suppl):1995–2025 Concise review: mesenchymal stem cells: their phenotype Google Scholar Oral mucositis: a challenging complication of radiotherapy Part 2: diagnosis and management of mucositis Comparison of radiation-induced oral mucositis scoring systems Documentation of radiation-induced oral mucositis Strahlenther Onkol (1998) 174(Suppl 3):44–6 PubMed Abstract | Google Scholar Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy doi:10.1002/(SICI)1097-0142(19990515)85:10<2103::AID-CNCR2>3.0.CO;2-0 Assessing stomatitis: refinement of the Western Consortium for Cancer Nursing Research (WCCNR) stomatitis staging system An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy Int J Radiat Oncol Biol Phys (2000) 47:13–47 26. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) or licensor are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Thierry Muanza, dG11YW56YUB5YWhvby5jb20= Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. Volume 14 - 2024 | https://doi.org/10.3389/fcimb.2024.1477143 Oral mucositis is a common and debilitating oral complication in head and neck cancer patients undergoing radiotherapy resulting in diminished quality of life and potential treatment disruptions Oral microbiota has long been recognized as a contributing factor in the initiation and progression of radiation-induced oral mucositis (RIOM) Numerous studies have indicated that the radiation-induced oral microbial dysbiosis promotes the occurrence and severity of oral mucositis approaches that modulate oral microbial ecology are promising for the management of RIOM Probiotics as a relatively predicable and safe measure that modulates microecology have garnered significant interest we discussed the correlation between RIOM and oral microbiota with a particular focus on the efficacy of probiotics in the control of RIOM in order to provide novel paradigm for the management of this disease palifermin (keratinocyte growth factor-1) is the only drug that is approved by the FDA to relieve chemotherapy-induced oral mucositis in patients with malignant hematological diseases there remains a significant need for safe and effective means to prevent and treat RIOM we critically review the role of oral microbial ecology in the development of RIOM introduce the recent advance in the application of probiotics to the control of this disease and discuss the current limitations and future efforts to promote the clinical translation of probiotics in the management of RIOM According to Sonis, the pathophysiology of RIOM is a dynamic process consisting of five consecutive overlapping phases: initiation, primary damage response (inflammatory upregulation and activation), amplification of the damage responses, ulceration, and healing (Sonis, 2004; Elad et al., 2022) Radiotherapy can directly injure DNA and lead to apoptosis of epithelial cells while oxidative stress generates reactive oxygen species (ROS) that further activate pathways such as the nuclear factor-κB (NF-κB) pathway associated with mucositis leading to excessive production of pro-inflammatory cytokines and further damage to basal epithelial cells and submucosal tissues further exacerbating tissue damage and superimposing secondary infections that aggravate mucosal lesions The interplays between the oral microbiota and damaged mucosal tissues play an important role in the development of RIOM further support the causal effect of oral microbiota in the development of RIOM it can be speculated that radiotherapy per se induces an early mucosal inflammatory response along with alterations in oral microbiota and the dysbiotic microbiota in turn amplifies inflammatory response induced by radiotherapy and ultimately promotes the development of RIOM These strategies benefit the prevention and symptom alleviation but have limited efficacy and present challenges such as potential side effects and high costs there is still a need to explore more effective relatively safe and economical strategies to promote the management of RIOM Potential mechanisms of probiotics in the management of RIOM Clinical trials on probiotics for the management of RIOM Although the impact on oral microbial ecology was not reported the protective effects of this synbiotic mouthwash against RIOM are likely accredited to the direct action on oral microbiota and local immune response in the oral cavity As oral cavity is relatively a conserved ecological niche that may be exclusive to foreign colonizers, a reliable and persistent colonization of gut-derived probiotics administered per oral is arguable (Yli-Knuuttila et al., 2006; Meurman and Stamatova, 2007; Caglar et al., 2009) probiotic strains isolated from oral cavity may have an innate advantage of reliable/persistent colonization in the oral cavity and thus yield a predictable long-term protective effect against oral mucositis we also observed that approximately 1/3 of the S salivarius K12-treated patients still developed severe oral mucositis This heterogeneity in treatment outcome may be due to the difference in the treatment-naïve microbiota that has varied resistance to radiation and probiotic interventions salivarius K12 not only exerts probiotic activity via modulating microecology but also benefits the host through anti-inflammatory and immunomodulatory capability the heterogeneity in host response to the pleiotropic effects of S salivarius K12 may also explain the varied treatment outcome by this oral probiotic strain whether application of these probiotics can effectively tackle these concurrent oral complications and clinical challenges other than RIOM has yet to be investigated in well-controlled clinical trials there still lacks in-depth mechanistic studies with respect to the protective effects of probiotic on RIOM future studies with proper animal models and genetic tools are still needed to further delineate the radioprotective effects of probiotics at molecular and cellular levels the frequency/dosage/duration and delivery mode of probiotics could also significantly confound the efficacy of probiotics against RIOM which warrant more controlled clinical trials in the future to generate high quality clinical evidence cautions should still be taken particularly when probiotics are applied to immunocompromised or critically ill patients which will also be a promising direction for future research and development Accumulating evidence has shown the association between RIOM and oral microbial ecology and application of probiotics has shown beneficial effects on this disease Although the clinical outcomes of probiotics vary by specific strains way of delivery and regimen of radiotherapy they can effectively alleviate RIOM and improve patients’ quality of life likely via inhibiting the overgrowth of opportunistic pathogens regulating host immune response and promoting mucosal repair thus representing a promising adjunctive therapy for the better management of RIOM The author(s) declare financial support was received for the research This work was supported by National Natural Science Foundation of China (82370947) The author(s) declared that they were an editorial board member of Frontiers This had no impact on the peer review process and the final decision All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Mucosal microflora in head and neck cancer patients Antibiotic-induced gut microbiota depletion accelerates the recovery of radiation-induced oral mucositis in rats Strategies to mitigate chemotherapy and radiation toxicities that affect eating Immunomodulatory effects of probiotics on cytokine profiles PubMed Abstract | Crossref Full Text | Google Scholar Burden of oral mucositis: A systematic 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Copyright © 2024 Li, Li, Zheng and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited *Correspondence: Xin Xu, eGluLnh1QHNjdS5lZHUuY24= Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish In the French commune of Riom, the Tracks Architectes designed the renovation of a former tobacco factory "#HER," to create a new program dedicated to leather manufacturing The listed building dates back to 1877 and is located near the city center The "#HER" project aims to preserve the industrial and artisan heritage enhancing the envelope and roof of the old building which was declared a Historic Monument in 2004 While respecting the building's distinctive image the proposal eliminates additions such as service elevators and air extractors the architects aimed to "destroy as little as possible and build as little as possible." Moving away from conventional single-story workshop models, the Tracks Architectes developed a vertical approach incorporating interconnected levels that foster user connectivity incorporating patios and skylights allows natural light to enter the interior creating a welcoming and stimulating workspace The reuse of existing buildings aligns with sustainability criteria significantly reducing the carbon footprint the judicious choice of construction materials reflects traditional methods that minimise the ecological impact By maintaining the site's manufacturing purpose the intervention preserves and revitalises the site enabling contemporary production practices Renovation of a former tobacco factory by Tracks Architectes Project description by Tracks Architectes The project for the new leather’s manufacture in Riom is being established within a section of the town’s former Tobacco Factory the twenty or so buildings are bordered to the east by railway tracks and west by residential areas and intermediate housing The rehabilitation of the Tobacco Factory preserves and enhances the building's envelope and roof which have been listed in the Inventory of Historic Monuments since 2004 The project integrates itself humbly and discreetly within the existing structure Unlike the group's usual single-story workshops this building necessitates a multi-story leather’s manufacture facility A vertical design approach was therefore adopted to ensure an efficient and effective workflow and connectivity across all spaces The intervention aims to maintain the site’s manufacturing vocation and revitalize this industrial heritage by adapting it to contemporary production practices: "destroy as little as possible and build as little as possible." Unsightly additions (such as freight elevators and rooftop exhausts) have been removed and in keeping with the original roof trusses some roof sections have been replaced with skylights or an open patio bringing natural light into the heart of the workshops The new entrance is marked by grand openings that extend the existing ones a fully glazed footbridge now connects the first floors of the two buildings to make use of the attic space with its magnificent curved concrete framework skylights integrated into the sloping roof provide illumination for the workspaces the project significantly reduces its carbon footprint The use of bio-based materials (wooden structures hemp insulation) aligns with traditional construction methods while minimizing ecological impact (natural ventilation) the landscaping project creates a green setting for the site incorporating rainwater retention strategies and highlighting a selection of local plant species Tracks Mandataire Architectes Heritage Architect - ABDPAStructural Engineer - BATISERFFluids Engineer - BARBANELEconomist - BMFHigh Environmental Quality Engineer - TRIBUAcoustic Engineer - ALTIAKitchen Designer - BEGCLandscape Architect - LUC LEOTOINGCivil Engineer - OKARE INGENIERIE Les manufactures d'Auvergne.- Hermès Immobilier Guillaume Amat Archive REMODELING-RENOVATION This miniature from The Book of the City of Ladies by Christine de Pizan considered the first professional woman author in Europe is one of over 140 items in Medieval Women: In Their Own Words When researching potential items to include in the British Library’s current exhibition Medieval Women: In Their Own Words (on view through March 2 I was struck by the exceptional importance of books and documents for recovering women’s histories While many surviving artifacts from the Middle Ages were probably made and used by women they often tell us a great deal about the people who shaped and interacted with them The exhibition seeks to uncover the varied lives of women across society yet it is also an exploration of the close relationship between medieval women and written culture.  Letter from Joan of Arc to the citizens of Riom The opening of the Mortuary Roll of Lucy of Hedingham showing illustrations of the Crucifixion and the Virgin and Child; the soul of Abbess Lucy being lifted to Heaven; and the funeral of Abbess Lucy.  women authors were greatly outnumbered by male authors girls were rarely educated to the same level as boys works by female authors survive in a wide range of genres often voicing distinctly female perspectives Those on display in Medieval Women include works by Christine de Pizan (d the first professional woman author in Europe who disputed conventional representations of women in male-authored literature; Hildegard of Bingen (d who described her ideas about God through feminized imagery; Gwerful Mechain (d a Welsh poet who celebrated female sexuality in her rollicking “Poem on the Vagina”; and Ḥafṣa bint al-Ḥājj ar-Rakūniyya (d a poet from Granada who wrote in Arabic and countered the effusive sentiments of her lover Abū Jaʿfar with coolheaded reserve.  there were probably more medieval women authors than we realize owing to the combined effects of religious censorship and anonymity It is sobering to think how close we came to losing the works of English mystics Julian of Norwich (d Julian of Norwich wrote two versions of her Revelations of Divine Love the first known female-authored work in the English language The “Short Version” survives in just one medieval copy while the “Long Version” survives only in seventeenth- and eighteenth-century copies made by exiled English nuns in France (probably from a single now-lost medieval manuscript) which was discovered in 1934 (allegedly while the owners of a country house were searching for ping-pong balls) it was known only from a series of extracts stripped of Margery’s voice and biographical details that were published in the early sixteenth century Widespread suspicion of women’s writings and centuries of religious upheaval were nearly enough to obliterate these important works How many more medieval women’s writings have we lost entirely Most extant documents from the Middle Ages contain more formal types of texts an unparalleled cache of over 1,000 letters belonging to a fifteenth-century Norfolk gentry family They reveal women juggling the demands of domestic life and social advancement from shopping lists and love matches to armed skirmishes against rival families They also include the first surviving Valentine’s letter in English sent by Margery Brews to her “right worshipful and well-beloved Valentine” John Paston in February 1477 with an inscription naming the female scribes in the lower margin.  perhaps the most famous woman from the Middle Ages is vivid in the popular imagination in part because her defiant words are preserved in the records of her heresy trial after which she was burned at the stake in 1431 A letter from earlier in her short but brilliant career as a spiritual visionary and military leader is on display in the UK for the first time as part of this exhibition on loan from the Archives municipales de Riom Joan sent the letter to the citizens of Riom entreating the city to send military supplies Joan dictated her letter to a scribe but signed her name Little connects us more powerfully to a historical person than seeing their signature the authentic mark of their presence in the world We can see women’s influence in book culture even when their own words do not survive rates of book ownership increased dramatically and women are recognized as key drivers of this change Elite women often patronized literature; for example commissioned the first book printed in English Caxton’s Recuyell of the Histories of Troye (1473) The exhibition includes a personalized treatise that Margaret commissioned from her almoner (or alms distributor) It takes the form of a dialogue between Margaret and Christ as illustrated in the beautiful frontispiece which shows them conversing in her bedroom Some of the most poignant traces of women in books reveal their physical touch manuscripts containing the Passion (or life story) of St were effective amulets for women giving birth A copy of the Passion of St Margaret made in fourteenth-century Padua ends with a childbirth prayer beginning “Exi infans Christus te vocat” (Come forth infant This is accompanied by a picture of a birthing scene that has been moistened and smudged probably by the devotional kissing of women hoping for a safe birth.  left: A childbirth prayer at the end of the Passion of St Margaret with a picture of a birthing scene that has been smudged likely by women who used it as a devotional to pray for a safe pregnancy right: An illustration of Margaret of York kneeling before the Resurrected Christ from Dialogue de la duchesse de Bourgogne à Jésus Christ.  Book production was another area in which women were active A majestic gradual (choir book for the Mass) from the Cistercian Abbey of Seligenthal contains inscriptions stating that a thirteenth-century nun named Elisabeth first wrote the manuscript choir mistress of the convent for thirty-five years As well as demonstrating these women’s scribal and musical skills the inscriptions suggest that the manuscript was in use at the abbey for at least 200 years.  The introduction of movable type printing to Europe in the fifteenth century created opportunities for women in the printing industry and their contributions are generally invisible The first woman in Europe to print a book under her own name was Estellina Conat Estellina printed the first edition of Jedaiah Ben Abraham Bedersi’s Beḥinat ha-‘Olam (The Contemplation of the World) a Hebrew poem written after the expulsion of Jews from France in 1306 or printer’s statement at the end of the book the wife of my worthy husband Abraham Conat printed] this book.” She used the word “katavti” (wrote) because no Hebrew term for printing existed yet.  The British Library is fortunate to be one of the world’s great repositories of words we were keen to use as many different sources as possible to recover the lives of medieval women While books and documents are not the only items on display—there is and even a lion’s skull—we hope that visitors will be as excited as we were to discover that medieval books have such vital and little-known stories to tell.   out-of-print and rare books in nearly all subject areas Log in via email All your bookmarks will be available across all your devices Password must be 8 characters long including one capital letter Please confirm your email address and we’ll send you a link to reset your password Single account access for STIRworld.com,STIRpad.com and exclusive STIRfri content Verification link sent to check your inbox or spam folder to complete sign up process or opt for the best experience by closing this banner For more detailed information please read our Privacy Policy the exhibition showcases Italian designer Matteo Cibic's works in ceramic creating an eight-part journey of self-examination by Bansari PaghdarPublished on : Nov 13 The French art museum has showcased several designers and contemporary artists since its establishment, but Double Paradiso is the first exhibition dedicated to an Italian designer since the Made in Italy exhibition in 1986 The vestibule greets visitors with the show's second section where an eccentric bust of Pinocchio—embodying the dreams pride and weaknesses of oneself—stands as the primary subject of Double Paradiso It presents itself as an amusing reinterpretation of the ancient Roman bust featuring motifs inspired by contemporary Italian earthenware One might feel strange yet excited to arrive at the otherworldly apothecary that is The Theatre of Envy, as glass poison vases powders and pill containers sit idly behind glass panes chance and fate and poses a question for all who find themselves taken with the 'theatrical game' of his 'ambivalent symbolism'—do these vases hold a rosier future or does a dark fate await those who dare to taste their contents urging guests to explore the museum and its contents with a different perspective while meditating Showcasing over two decades of expertise in working with ceramic Cibic shapes the whimsical utopian bestiary setting of the Double Paradiso featuring characteristic arches that puncture a concrete cube the project includes three distinct movie theaters with 543 seats and a conference room that holds 112 people tracks architectes divided the project into two intersecting volumes that complement each other in their texture the first volume borrows his height from the wall of the existing enclosure ‘volvic stone’ offers a material available to be reused as large aggregates for the concrete of the outer sails of the first low volume the facade is intervened and arches are cut through showing the building behind.the facade thus marks the footprints of the new construction and reinterprets the use of local material in a contemporary way a second lighter volume with complementary proportions imposes itself as an urban landmark orchestrated by the punctured wall a concrete white monolith makes up the building yet holds an apparent fragility due to its succession of arches it stands in front of the ‘jardin de la culture’ and the ‘couvent des redemptoristines’ the facade’s strong graphic identity strengthens the fantasized image of a cloister around the large green parvis the volumetric division opens the large gallery of the cinema hall to the outside the architects explain that though the facade arches ‘the invitation is made: go through these monumental doors,’  and into the sun-bathed living space that hosts a large exhibition hall the generous and continuous space is extended by a covered outdoor gallery perforated by the arches this plan’s organization is inspired by the cinematic realm having circulation paths wind around rooms and volumes architecture: tracks architectes designboom has received this project from our ‘DIY submissions‘ feature, where we welcome our readers to submit their own work for publication. see more project submissions from our readers here. happening now! partnering with antonio citterio, AXOR presents three bathroom concepts that are not merely places of function, but destinations in themselves — sanctuaries of style, context, and personal expression. The squad will train at France’s national performance centre – INSEP – over the winter.  A further four will be eliminated in January 2024, leaving eight – four men and four women – to compete in the next international season. The final six-athlete team for the 2024 Olympics will be selected just ahead of the Games and that’s what I did,” said former European Champion Barbelin who beat the national 72-arrow qualifying record by one point with 676 during the trials “It was great to finally manage to beat the French record that I had been trying to beat for a long time.” The field of archers was cut to just eight in each gender after four days – and eight 72-arrow 70-metre rounds – of competition the recurve men were led by 16-year Baptiste Addis “I maintained a consistency over the first four days, with four rounds of more than 680 points, of which I am really proud,” he told journalists from the French federation I was reaching my mental and physical limit but I still gave everything but the goal is to now be in the world’s top Addis was individual bronze and team gold medallist with France’s under-18 team at the recent World Archery Youth Championships in Limerick The large French clubs of Nîmes and Riom both provide four archers to the squad Announcement available on the French federation website. Archive TECHNOLOGY among several located in the agglomeration’s territory and will provide an economic boost to the area,” said Hermès reaffirming “its strong connection to the Auvergne region where it relies on several local partnerships.” Hermès already operates a facility in the region and the new factory will grow the total number of Hermès jobs in Auvergne to 500 The adoption of new digital technologies has been central to these changes In the context of the broader debate about the effects of technological change on employment and jobs (see, for example, Acemoglu and Restrepo, 2019) a key question relates to how Covid-19-induced technology adoption has and will affect workers create new tasks and change the demand for skills and can complement (certain types of) labour the adoption of marketing automation technologies powered by artificial intelligence (AI) makes it possible for businesses to leverage data at scale and raises the demand for skills associated with data analytics A survey of recent studies on the effects of automation on labour demand finds more empirical support for a positive impact on employment overall at the firm level (Aghion et al, 2022) Automating firms can become more productive and grow generating new jobs (potentially at the expense of their competitors though relationships at the industry level are also positive) The Centre for Economic Performance (CEP) and the Confederation of British Industry (CBI) have conducted two bespoke business surveys, the first in July 2020 and the second a year later nature and effects of technology adoption in response to the crisis The second survey included a series of questions that sought to shed light on how technology adoption since the onset of the pandemic has affected the workforce. The rise of working from home and the associated increased flexibility have clearly been enabled by the widespread adoption of remote working technologies such as Zoom or Microsoft Teams But this work set out to explore how effects on workers vary according to the types of technology introduced or the characteristics of firms doing the adopting As set out in a previous Economics Observatory article, the effects of a crisis on technology adoption are theoretically ambiguous (Valero and Van Reenen, 2021) But the evidence to date suggests that the pandemic has accelerated technology adoption in firms in part due to the nature of the crisis (requirements for social distancing) and the readiness of digital technologies that allowed firms and workers to adapt quickly in sectors where this is feasible reaffirmed the strong innovation response among UK businesses Three-quarters of firms adopted digital technologies over this timeframe (see Figure 1) Over half (55%) had adopted new digital capabilities and nearly 70% had adopted new management practices over 60% of firms had introduced new products and services while the adoption of digital technologies and management practices occurred early on (March-June 2020) at many firms a large share of firms continued to innovate beyond the initial lockdowns the share of firms adopting new digital capabilities was constant while product innovation increased over time But were these activities induced by the pandemic And are new processes and products here to stay beyond it Most firms considered that the pandemic had accelerated their innovation plans and between 11% and 34% of firms (across innovation types) reported that the pandemic actually prompted them to innovate most firms expected them to outlast the pandemic the reported effects on business performance are broadly positive 28% of businesses had adopted new technologies (the share is higher among businesses with ten or more employees) While this is substantially smaller than the 75% in Figure 1 it still represents a rise compared with pre-pandemic ‘process innovators’ discussed above 46% of the BICS sample answered that they were ‘not sure’ when asked about technology adoption – versus a negligible share in the CEP-CBI survey where the respondents were perhaps more used to being asked detailed questions on technology-related issues While remote working technologies are perhaps the most commonly discussed among adopters in the CEP-CBI survey new technologies also related to a range of business functions followed by people management and remote working Technologies for remote working – such as video conferencing or collaboration technologies – were the most adopted specific technology types either alone or in ‘bundles’ with other technologies including online marketing tools (for example a new website or social media platforms/e-commerce) In terms of overall impact on the size of the workforce most firms (63%) reported that newly adopted digital technologies had no impact (see Figure 3) The share saying that they had reduced the need for workers (16%) was similar to the share reporting an increased need (13%) Given that the furlough scheme was in operation during this period – and a high share of survey respondents had accessed it – it was potentially too early to detect changes with respect to employment resulting from new digital processes There was more evidence of changes in working practices An increase in flexible working stands out productivity and worker satisfaction were also reported to have risen in over 40% of firms that adopted new technologies Almost half (45%) stated that they had reorganised staff or reallocated employees to new tasks as a result of new technology adoption And while most firms reported no change to working hours 18% reported a rise due to the implementation of new technologies There were also associated changes in hiring activity. Over a quarter reported an increase in hiring in specialist skills, and a similar share stated that they were hiring from a broader geography than before the pandemic (see Figure 4). This is a phenomenon enabled by increased remote working and brings implications for the future shape of cities(Nathan, 2021) Remote working was still prevalent in July 2021 and at that point – before Omicron emerged and guidance changed – expectations for working patterns for January 2022 looked very different to pre-pandemic with one to two days at home being the most popular option among firms Firms that had adopted new digital technologies prior to the pandemic were more likely to report improved worker productivity because of new technology adoption controlling for other key business characteristics But they were less likely to report an increase in flexible working had fewer ‘teething’ problems with new technologies and already had flexible working practices in place firms with a higher degree share among employees were more likely to report an increase in overall workforce size as a result of technology adoption consistent with new digital technologies and skills being complementary There were also different effects according to the type of technology being adopted Where firms adopted technologies relevant for people management remote work or other ‘business-as-usual’ tasks they were more likely to report increased flexible working Firms that adopted remote working technologies also saw a rise in average working hours. This is consistent with other studies that have shown that home workers have put in more hours since Covid-19 (see, for example, Barrero et al, 2021) Firms that adopted new technologies relevant for research and development (R&D) functions were more likely to report an increase in workforce size Covid-19 has increased technology adoption and other types of innovation in businesses and these activities are affecting the workforce Firms considered that skills constraints were the biggest barrier to technology adoption in the second CEP-CBI survey perhaps reflecting more widespread shortages at that time Continued digitisation in businesses will occur at the same time that the move towards net-zero emissions brings changes to strategies, operations and jobs environmental considerations are being taken into account to either a great or some extent by around two-thirds of firms in the CEP-CBI survey This is happening across a number of areas including decisions on technology adoption working practices and office design or location It presents an opportunity for a joined-up approach to business support and skills policies to boost productivity growth in an inclusive and sustainable way The new CEP-CBI survey data provide a first look at the potential effects of pandemic-induced technology adoption on the workforce There are well-known caveats in the analysis of self-reported performance measures we might expect biases that result in firms over-reporting socially desirable behaviours (such as positive effects of adoption on company or worker performance) and under-reporting socially undesirable behaviours (such as a reduction in headcount) But knowing the responses were anonymous should mitigate these effects Merging business surveys with administrative data will allow researchers to track the actual performance of firms and trace the effects of technology adoption on employment and other worker outcomes over time Privacy Policy & Terms and Conditions Web Design Grizzly French fashion house to open factories in Louviers Sormonne and Riom as bags become must-haves is opening three new factories as it struggles to keep up with demand for its £5,000-plus Birkin and Kelly handbags The company said on Friday it planned to open new leather goods factories in the French towns of Louviers Sormonne and Riom before 2024 in order to increase and speed up its production of the expensive bags It has also recently opened its first leather-working school to train more craftspeople in the art of handbag making The company, which already has more than 4,300 leather workers on its staff, said it was hiring more than 400 artisans each year. However, Hermès said it needed far more to keep up with demand for its handbags, which has jumped during the Covid pandemic as soaring stock markets have left the world’s richest people with a lot more disposable income The bags have become must-have collectibles for the super-rich and celebrities, including Victoria Beckham, Katie Holmes, Rita Ora and Kelly Brook, with some women owning hundreds of the most sought-after designs Rare Hermès bags have also proven extremely popular at auction, with some selling for almost £300,000 and we have a product that is very handcrafted,” the executive chairman of Hermès “It takes 15 hours [to create] an Hermès bag I’m not going to start doing them in 13 hours to raise production.” Dumas said there was often a long waiting list for the bags we’re always very sad when we have to say no to our customers because we don’t have that.” He ruled out raising prices The lack of handbag stock led to a 5.4% drop in fourth-quarter sales at its leather goods and saddlery division which accounts for almost half of total sales The news sent Hermès shares down 7% on Friday before recovering slightly to a 5% decline which was still its biggest one-day fall since 2016 Overall sales rose to €2.38bn in the three months to December with American and Chinese shoppers driving strong growth but were below analyst forecasts of €2.53bn The slow growth at Hermès contrasts with an acceleration at other luxury groups such as LVMH Moët Hennessy Louis Vuitton which have posted much better-than-expected results BackLe Mans 2008 - The Audi R10 TDIs at the Ford turnA look back at an unusual event that took place during 24 Hours week in 2008: the official Audi R10 TDIs at a photo session in the Ford turn Related News24h Le Mans02/05/2025 The trailer for the documentary ‘American Thunder: NASCAR to Le Mans’ unveiledIn 2023 during the Centenary edition of the 24 Hours of Le Mans ‘American Thunder: NASCAR to Le Mans’ retraces this adventure in a full-length documentary broadcast exclusively on Prime Video on 12 June The second round of the 2025 European Le Mans Series (ELMS) takes place this Sunday 4 May at the Circuit Paul Ricard An impressive 44 cars are expected on the grid with a large French contingent on home soil in terms of both drivers and teams For the 93rd edition of the Le Mans 24 Hours (11-15 June 2025) the #59 McLaren 720S LMGT3 Evo entered by United Autosports in the LMGT3 class will feature a unique livery: the Meningitis Flag The aim of this livery is to raise awareness of a disease that is all too often overlooked: meningitis The Automobile Club de l’Ouest is proud to announce that Roger Federer the revered champion and global sporting icon will don the mantle of official starter at the 93rd 24 Hours of Le Mans the fourth round of the FIA WEC World Endurance Championship Get our news on your inbox! Suscribe x MercoPress, en Español Montevideo, May 6th 2025 - 06:30 UTC An impartial group of independent international observers Referendum International Observation Mission (RIOM) will monitor the referendum on the political future of the Falkland Islands on Sunday and Monday The team is free from external pressure and will determine whether the vote is free and fair and representative of the Islanders’ will The RIOM mission is led by Head of Mission Brad Smith and Deputy Head of Mission Juan Manuel Henao and will include a number of elected officials technical experts and eminent persons from the Americas and South Pacific A press release from the group said: “International observation standards will be observed as well as applicable Falkland Islands election laws and regulations A final Referendum Report is expected two weeks after the vote Who appointed this “Observation Mission” Commenting for this story is now closed.If you have a Facebook account, become a fan and comment on our Facebook Page The Swiss pharmaceutical services firm Carbogen Amcis will undertake a $110 million expansion program adding an active pharmaceutical ingredient (API) facility at its site in Hunzenschwil and building a new facility for parenteral drug products near its site in Riom Carbogen plans to install 12 vessels by 2024 with capacity ranging from 630–4,000 L designed to supply finished drugs for clinical trials and small-scale commercial use will include two automated lines—one for liquid filling and lyophilization and one for liquid-form production—when it opens in 2023 Carbogen also plans to add chromatography equipment and laboratories Carbogen CEO Mark Griffiths says the API expansion addresses a need for more capacity after several years of growth The finished-drug facility targets what he sees as an underserved need for sterile drug production in high-tech areas such as oncology and antibody-drug conjugates at late-stage clinical ACS’s Basic Package keeps you connected with C&EN and ACS $80 Regular Members & Society Affiliates ACS’s Standard Package lets you stay up to date with C&EN ACS’s Premium Package gives you full access to C&EN and everything the ACS Community has to offer Carbogen plans to install 12 vessels by 2024 with capacity ranging from 630–4,000 L The finished-drug facility targets what he sees as an underserved need for sterile drug production in high-tech areas such as oncology and antibody-drug conjugates at late-stage clinical and early-commercial scale “We see a big appetite for customers that want small commercial batches Griffiths anticipates continued growth in pharmaceutical services as companies seek to move production outsourcing back to the US and Europe from China and India—a trend that has accelerated during the pandemic “They are wandering around looking for capacity But he says the primary motivation for the expansion is a forecast of continued demand from small-to-midsize biotech innovators which have fueled the firm’s growth in recent years This article has been sent to the following recipient: Sign up for C&EN's must-read weekly newsletter Copyright © 2025 American Chemical Society Hermès has opened its latest leather goods factory and is the company’s 23rd leather goods factory in the country Riom forms a hub with the nearby Sayat leather goods factory which has been producing leather goods for more than 20 years Hermès has opened 12 leather goods workshops across France Three other projects are currently underway – in L’Isle d’Espagnac in Charente and Charleville-Mézières in the Ardennes – for which recruitment and training are ongoing Hermès said it is dedicated to keeping the majority of its production in France through its 60 production and training sites and to developing its network of next to 300 stores in 45 countries Give your business an edge with our leading Leather International Give your business an edge with our leading industry insights View all newsletters from across the Progressive Media network © Business Trade Media International Limited The Government’s commitment to achieving net zero greenhouse gas emissions by 2050 will mean investment across the economy: from the decarbonisation of buildings and surface transport This briefing note explores the impact that the net zero transition will have on the UK labour force by setting out the types of ‘green’ and ‘brown’ jobs that are most likely to experience change analysing core differences in the workers that are employed in these jobs and in the type of tasks that they typically perform We also examine how green and brown jobs have changed over time and in particular consider the origins of green job workers today including the share of workers that move from a brown job into a green job and the key characteristics of those making such a move For all research queries about this report, please contact Jonathan Marshall. For press queries, please contact the Resolution Foundation press office Jonathan MarshallSenior Economist,Resolution FoundationEmail Jonathan Resolution Foundation, 2 Queen Anne’s Gate, London SW1H 9AA   |   Privacy and Terms   |   Website by Wholegrain Digital We use cookies. Read more about them in our Privacy policy. With no formwork required, and customisation costing no more, there could be big time and cost savings on site Researchers in Switzerland have pioneered a method of 3D printing structural concrete columns at high speed using minimal material and without formwork. Masters students on the architecture and digital fabrication programme at ETH Zurich developed design software and robotic extrusion techniques to print each of nine unique 2.7m tall columns in less than two and a half hours. The freeform undulating structures were created with support from the National Centre of Competence in Research into Digital Fabrication for installation at the ‘Concrete Choreography’ dance show at the Origen Festival in Riom. Each column was printed in multiple thin layers by a specially adapted six-axis manufacturing robot suspended from a gantry. The robot extruded a mix of regular concrete and additives designed to control the material’s behaviour and accelerate the curing time. The process developed by researchers involves the formation of honeycomb-like voids within the structure to help stabilise it while minimising material use. However, on this occasion the voids were subsequently filled in with ordinary concrete, with a reinforcement cage through the centre of the columns, to ensure a strong bond with the printed shell. ‘The software enables us to distribute the concrete exactly where it is needed structurally, which allows us to save a lot of material,’ says Dillenburger. ‘Our vision is to be able to strategically place concrete and not pour massive concrete elements in the conventional way. In theory, the technique could save up to 80% of concrete, compared with conventional construction.’ ETH students were asked to explore how emerging digital technologies could inform the design of a contemporary column order, similar to those devised by ancient Greeks and Romans. The columns had to be visually expressive and form a key element of the stage design at the festival. The resulting rippled, curvaceous columns are reminiscent of Antoni Gaudi’s work, and Dillenburger believes the famed Spanish architect would have been keen to exploit 3D concrete printing technology were he alive today. ‘Gaudi was very experimental with engineering and state of the art technology, simulating  and “form finding” his constructions using advanced physical models. Today’s digital computational design and robots make it possible to build very differentiated and unique architecture, so I  think he would be open to the process.’ updates and our weekly newsletter – all designed to bring you the best stories from RIBAJ.com Sam Bennett’s hopes of making the Decathlon AG2R La Mondiale team for the Tour de France in July will bolstered when he roared back to form at the recent Four Days of Dunkirk And now the Irishman looks like his name will definitely be on the team sheet announced for the French Grand Tour in coming weeks after being included in his team’s selection for the upcoming Critérium du Dauphiné (2.UWT) which gets underway in Saint-Pourçain-sur-Sioule on Sunday is the traditional fine-tuning outing for riders with hopes of making their Tour teams It will be a much harder outing than the Four Days of Dunkirk tougher stages and much higher quality opposition if Bennett’s recent wins were the first step in returning to the highest level – which means winning again on the Tour – then his inclusion in the Critérium du Dauphiné team is the next development in that process in a season when his team is enjoying an incredible run of success which also includes Edvald Boasson Hagen and Oliver Naesen both of whom can be crucial support riders for the Irishman in the sprints Dorian Godon and Nico Prodhomme and is a strong unit with Godon also showing a turn of speed – and skill in the bunches – that could aid Bennett or deliver stage wins for himself in France next week Bennett has ridden the Dauphiné three times in his career and has He was victorious on stage 3 of the 2019 edition where he saw off Wout van Aert (Jumbo Visma) and Davide Ballerini (Astana Pro Team) for victory A stage win in the 2024 edition would really confirm his return to top level after his recent success and he may get a chance as early as the first stage and perhaps stage 5 to Saint-Priest look like the only two obvious stages for the fast men the field is not expected to be stacked with sprinters though Mads Pedersen is already confirmed for Lidl Trek We’re determined to make stickybottle.com much better for your enjoyment So become a ‘Stickybottle Supporter’ now from just €5 per month We’ve grown our audience significantly in recent years but the advertising market has become harder and harder each year In order to survive and grow – and create much better content – we need to develop an income from our readers By signing up to become a ‘Stickybottle Supporter’ you’ll be helping to secure independent coverage of Irish cycling for years to come Every cent collected from readers will be used to directly fund content Sign Up