[Survey by SFRO, SNRO and AFPPE about the evolution of the radiation therapist profession in France]. / Enquête SFRO­SNRO­AFPPE sur l'évolution du métier de manipulateur exerçant en radiothérapie en France.

PURPOSE: As part of the multidisciplinary team, radiation therapists are in charge of elements of treatment preparation and delivery of radiotherapy to cancer patients. Helping scientific and technological improvements, more and more patients with cancer were treated with radiotherapy including hypofractionnated radiotherapy, that explain the increase of demands on services. The professional impacted by this increase of demands are radiation oncologists and medical physicists. The opportunity to push forward the radiation therapist's competencies appears with the possibility to shift them some tasks. In this context, a first work was performed with objectives to have an overview of the tasks shifted to radiation therapists in France, the tasks that they could perform but also to evaluate some criteria of job satisfaction. MATERIAL AND METHODS: The committee of "new status and value of status" including six radiation oncologists (the French society of radiation oncology [SFRO] et national union of radiation oncologists [SNRO]) and six radiation therapists committee members of the French association of radiation therapists (AFPPE), built a questionnaire including three parts: demographic characteristics, tasks shifted and job satisfaction criteria. In total, the questionnaire included 19 questions and 24 items assessed with a four point-Likert scale (ranging from "completely disagree" to "completely agree"). This survey, formatting with google form, was tested by the committee members and the final version was sent to the SFRO, AFPPE and SNRO members, before being disseminated on the social networks. RESULTS: From November 18th 2022 to December 31st 2022, 492 responses were received (response rate=18.3%): 55 % of the respondents had at least 11 years of experience in radiotherapy. The respondents worked in different type of health facilities (36 % in specialized cancer centres, 19.5 % in private centers, 17.5% in university and general hospital, 10.2% in general hospital). More than » of the respondents had a teaching lecturer activity, 20% had a management team activity and a research activity for 18%. Less than 10% of the respondents had another degree than that of radiation therapist: university degree (n=27), degree in dosimetry (n=11) and master (n=3). More than 76% would like to be trained and to have access to the advanced practice, more than 50% would like expend competencies with a university degree, 30% with a master and 67% would like to participate in research. Forty-two percent of the respondents were involved in a task shifting (excluding decree relating to acts and activities carried out by radiation therapists) and among the radiation therapists non-involved, 63% would be interested in being. Regarding job satisfaction, 53% of the respondents were satisfied with their job and their salary and 68% believed that their job occupation is in line with their professional aspirations. More than 2/3 of the respondents described a significant workload and mental load, 53% thought to have time for their patient care and 70% felt some organisational difficulties. CONCLUSION: This survey shows: (i) A significant involvement of radiation therapists in the task shifting; (ii) A very strong demand for career development, in particular with existing degrees or to be created degree such as advanced practice; and (iii) The need to reinforce a job satisfaction for almost the half of the respondents, linked to a workload, a mental load and some organisational difficulties.

Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism.

Cilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein regulatory complex (N-DRC), which links adjacent doublet microtubules and regulates and coordinates the activity of outer doublet complexes. Despite its critical role in cilia motility, the assembly and molecular basis of the regulatory mechanism are poorly understood. Here, using cryo-electron microscopy in conjunction with biochemical cross-linking and integrative modeling, we localize 12 DRC subunits in the N-DRC structure of Tetrahymena thermophila. We also find that the CCDC96/113 complex is in close contact with the DRC9/10 in the linker region. In addition, we reveal that the N-DRC is associated with a network of coiled-coil proteins that most likely mediates N-DRC regulatory activity.

[Radiation therapists shortage in France: Organizational consequences and difficulties in deploying new missions and/or tasks delegation]. / Métier de manipulateur en radiothérapie en tension en France : conséquences organisationnelles et difficultés à déployer de nouvelles missions et/ou délégation de tâches.

PURPOSE: Radiation therapists shortage has been evaluated at national level in France, specifically in oncology radiotherapy, in terms of: (i) organizational adaptations, (ii) impact on patients care, and (iii) difficulties in deploying new missions and/or tasks delegation. MATERIALS AND METHODS: French professional organisations representing radiation therapists - SFRO, SNRO and AFPPE - sent their members a national survey (ten questions on 32 items). RESULTS: From 18 November 2022 to 31 December 2022, 55 responses were received (response rate: 31%) from radiotherapy managers or department heads; 51% had a structure comprising three to five treatment rooms (receiving 500 to 1000 patients per year [36%], or 1500 to 2000 patients per year [33%]). Activities performed were intensity-modulated radiotherapy (100%), stereotaxic radiotherapy (85%), brachytherapy (40%), adaptive radiotherapy (34%). These structures described consequences in closing machine time for 25% of them (reduction of the hourly volume greater than 10% in 57%) with the following consequences in the last 6 months: (i) an extension of the period of medical care (78%), a closing of one or more accelerators (50%) and the development of moderate hypofractionation scheme or extreme hypofractionation (50%). In current functioning, linear accelerators can deliver treatments with a team of two radiation therapists per room for a short day (43%) or two to four radiation therapists per room teams for a long day (40%). During the last 6 months, there has been a 10% increase in linear accelerators operating with a single team. (ii) regarding treatment planning: 16.4% reported a decrease in the opening amplitude (less than 20% in 44% of cases, from 20 to 50% in 33 % of cases). The initial scheduling of appointments for radiotherapy sessions was carried out by radiation therapists in 84% of the departments in current functioning (0.1 to 1 FTE dedicated to this activity in 62% of the departments). Over the last 6 months, there has been a clear reduction in the number of dedicated FTEs: [FTE=0.1 to 1]=-8%; [FTE=0]=+7%. (ii) Regarding tasks delegation (excluding the decree on acts and activities carried out by the radiation therapist): organ at risk delineation is partially performed by radiation therapist in 26% of the centres; caregiver support time in 78% (56% totally or 22% partially). This activity has been reduced by 42%. Seventy-five percent of departments want to develop new techniques, patient-centered approaches (44%), implement task delegation (organ at risk delineation: 58%; weekly consultations: 67%; positioning imaging validation: 71%), and 78% of departments are interested in developing advanced radiotherapy practice. However, the number of radiation therapists is considered insufficient in their implementation in 76% of cases (one to two FTE missing for 72% of structures). CONCLUSION: This survey shows a significant impact of radiation therapist shortage in radiotherapy oncology care (treatment delays, access to caregiver support time, workload on treatment teams), and represents a major obstacle to the development of radiotherapy structures.

[The first steps towards advanced practice for radiation therapists]. / Les prémices de la pratique avancée pour le manipulateur en radiothérapie.

The implementation of advanced practice in RT requires evidence regarding the clinical practices of radiation therapists (RTT) in the field. In this context, the goal of this article is to report the roles assigned to RTT in order to meet the demands of patients, RT services, and/or healthcare professionals. As part of the French Society of Oncologic Radiotherapy's congress, the Radiotherapy Committee of the French Association of radiographers presented a scientific program encompassing three main themes: patient follow-up by a RTT, the expertise of an RTT in Image Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART), and the involvement of a RTT in research. This article presents an overview of five oral presentations that highlight concrete examples of roles assigned to RTTs in these specific domains. The follow-up of patients has been assigned to RTT. Research and development have been recognized as activities in which RTT play a significant role. The establishment of RTT specializing in IGRT has been reported to facilitate decision-making and is essential in ensuring professional expertise. Lastly, there is a need to enhance RTT skills in adaptive RT to support the implementation of this technique. These roles described as advanced practice meet needs and require a specific organisational framework and appropriate education and training (master type). Activities such as post-RT follow-up, validation of positioning imaging, delineation, writing research protocols, and involvement in the development of technological innovations were identified as essential tasks that can be assigned to RTT.

[Impact of a positive coronavirus diagnostic test on the radiotherapy patient journey at Gustave-Roussy institute]. / Impact d'un test de diagnostic du coronavirus positif sur le parcours du patient en radiothérapie à l'institut Gustave-Roussy.

PURPOSE: The coronavirus disease 2019 (COVID-19) epidemic continues to spread exponentially around the world. Cancer patients have a higher risk of commorbidity than the rest of the population. Radiotherapy departments are actively involved in the management of these patients, whether they have COVID or not, and it is recognized that the time taken to take charge and the continuity of treatment have a prognostic impact. The main objective was to assess the impact of the coronavirus on the treatment times of patients undergoing radiotherapy. MATERIAL AND METHODS: This retrospective study was conducted in the radiotherapy department of Gustave-Roussy institute (France) during the period from March 3, 2020 to January 12, 2021. Organizational changes, patient care times between the day of the scan and the last radiotherapy session as well as the time taken to take charge of patients between the first session and the last radiotherapy session has been studied. RESULTS: A total of 1183 patients were included, among which 60 had COVID-19. Patients were divided into four categories. Treatment times of patients who did not have COVID-19 and those of patients who did were not statistically significantly different. CONCLUSION: The organization of the radiotherapy department at the Gustave-Roussy institute is based on several points: carrying out preventive screening tests, protecting staff and patients and reorganizing the patient circuit. Thanks to the performance of diagnostic tests and the implementation of a specific workflow for patients with COVID, we ensure the continuity of patient treatment in complete safety without impacting treatment times.

Remodeling and activation mechanisms of outer arm dyneins revealed by cryo-EM.

Cilia are thin microtubule-based protrusions of eukaryotic cells. The swimming of ciliated protists and sperm cells is propelled by the beating of cilia. Cilia propagate the flow of mucus in the trachea and protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs) which attach to the doublet microtubules. The bending of cilia is driven by the ODAs' conformational changes caused by ATP hydrolysis. Here, we report the native ODA complex structure attaching to the doublet microtubule by cryo-electron microscopy. The structure reveals how the ODA complex is attached to the doublet microtubule via the docking complex in its native state. Combined with coarse-grained molecular dynamic simulations, we present a model of how the attachment of the ODA to the doublet microtubule induces remodeling and activation of the ODA complex.

[Cooperation protocol and advanced practice, an evolutionary perspective for the French radiation therapist]. / Protocole de coopération et pratique avancée, une perspective d'évolution pour le manipulateur en radiothérapie français.

For several years, the profession of radiographer has been unattractive and is in search of professional recognition. Increasingly complex therapeutic and diagnostic evolutions forces professionals to develop their skills to ensure quality and safe care for all patients. The primary role of the radiographer is to support patients and to accompany them during their examination or treatment, combining caregiver and technician's roles. Transversal missions and delegation of tasks are inherent to the profession but are not widely recognized. Cooperation between radiotherapy professionals is a response to offer the therapeutic radiographer/radiation therapist (RTT) opportunities in terms of attractiveness, career prospects, and increased skills. In radiotherapy, advanced practice activities already exist in some departments but require regulatory adjustments, in particular regarding the redistribution of the roles of RTT but also the status of these professionals. The formalization of these practices can be largely inspired by the many feedbacks around the world. This article aims to reflect the evolution's perspectives in the career of an RTT and on the valorisation of this profession in the current context.

[Application of a new methodology of a priori risk analysis in a radiotherapy department]. / Application d'une nouvelle méthodologie d'analyse de risques a priori dans un service de radiothérapie.

Since 2017, IRSN has been developing a new proactive risk analysis method. The Work Complexity Sharing and Exploration Spaces (EPECT in French) were tested for the first time in 2020 in the radiotherapy department of the Gustave Roussy Institute. The EPECT method makes it possible to anchor the analysis of risks incurred by patients in daily work situations and to involve the top management. The time required to involve the teams is comparable to or even less than that required for a conventional risk analysis. The cost/benefit ratio of the method seems to be advantageous because it provides access to numerous information on daily activities, which makes it possible to improve the safety of patient care in radiotherapy. The information gathered allows relevant actions to be envisaged at both the technical and organizational levels, and to be linked to departmental projects.

[Retrospective study on the intensification of hypofractionated radiotherapy: The organizational change]. / Étude rétrospective sur l'intensification des pratiques de radiothérapie hypofractionnée : le virage organisationnel.

PURPOSE: External radiotherapy process is a chain of steps in which each of them is carried out only if the previous one has been completed. The development of hypofractionation practices in recent years tends to increase the workload of the stages of preparation for irradiation and to decrease the number of fractions per patient. The purpose of this retrospective study is to analyze the evolution of these practices in a single centre and to assess the organizational issues involved. MATERIAL AND METHODS: All radiation therapy records management data were extracted from the Radiation Therapy Information System. Radiotherapy sessions were identified by patient and by ICD (International Classification of Diseases) code. The filling rate of the treatment equipment was calculated using actual data from the radiotherapy department. RESULTS: From 2015 to 2019, there was an increase in the number of scans (+16%), the number of patients treated (+11.6%) and the volume of hours available for treatment (+12%). Also, there was a decrease in the total number of fractions (-5%), in the average number of fractions performed per treatment sequence (-19%), in the occupancy rate of the machines (-7%) and in the average number of fractions performed per patient treated for malignant tumours of the bronchi and lung (-38%), digestive organs (-37%), secondary (-19%) breast (-15%) and prostate (-15%). The number of fractions administered per treatment sequence between 2015 and 2019 decreased significantly for patients in age groups [20-69] (P<0.001) and [>70] (P<0.001). CONCLUSION: A paradox appears between the increase in the total number of patients treated and the decrease in the loading rate of linacs. This shift of workload has an impact on the quality and safety of care and on the organizational and investment strategies. It also has an economic impact where the model of reimbursement is based on per fraction pricing. A reorganization of radiotherapy services is inevitable.

[Implementation of "never events" checklists in a radiotherapy information system]. / Mise en œuvre de listes de contrôle « never events ¼ dans le système d'information en radiothérapie.

In order to reduce the incidence of major accidents during external radiotherapy treatment, "never events" checklists have been incorporated into the "record and verify" system. This article details this process. Prospects for improvement are also proposed, including a peer-to-peer audit on the use of checklists and the availability of the radiotherapy information system manufacturer to collaborate in this process to secure the patients' journey.

Laser ablation of the zebrafish pronephros to study renal epithelial regeneration.

Acute kidney injury (AKI) is characterized by high mortality rates from deterioration of renal function over a period of hours or days that culminates in renal failure. AKI can be caused by a number of factors including ischemia, drug-based toxicity, or obstructive injury. This results in an inability to maintain fluid and electrolyte homeostasis. While AKI has been observed for decades, effective clinical therapies have yet to be developed. Intriguingly, some patients with AKI recover renal functions over time, a mysterious phenomenon that has been only rudimentally characterized. Research using mammalian models of AKI has shown that ischemic or nephrotoxin-injured kidneys experience epithelial cell death in nephron tubules, the functional units of the kidney that are made up of a series of specialized regions (segments) of epithelial cell types. Within nephrons, epithelial cell death is highest in proximal tubule cells. There is evidence that suggests cell destruction is followed by dedifferentiation, proliferation, and migration of surrounding epithelial cells, which can regenerate the nephron entirely. However, there are many unanswered questions about the mechanisms of renal epithelial regeneration, ranging from the signals that modulate these events to reasons for the wide variation of abilities among humans to regenerate injured kidneys. The larval zebrafish provides an excellent model to study kidney epithelial regeneration as its pronephric kidney is comprised of nephrons that are conserved with higher vertebrates including mammals. The nephrons of zebrafish larvae can be visualized with fluorescence techniques because of the relative transparency of the young zebrafish. This provides a unique opportunity to image cell and molecular changes in real-time, in contrast to mammalian models where nephrons are inaccessible because the kidneys are structurally complex systems internalized within the animal. Recent studies have employed the aminoglycoside gentamicin as a toxic causative agent for study of AKI and subsequent renal failure: gentamicin and other antibiotics have been shown to cause AKI in humans, and researchers have formulated methods to use this agent to trigger kidney damage in zebrafish. However, the effects of aminoglycoside toxicity in zebrafish larvae are catastrophic and lethal, which presents a difficulty when studying epithelial regeneration and function over time. Our method presents the use of targeted cell ablation as a novel tool for the study of epithelial injury in zebrafish. Laser ablation gives researchers the ability to induce cell death in a limited population of cells. Varying areas of cells can be targeted based on morphological location, function, or even expression of a particular cellular phenotype. Thus, laser ablation will increase the specificity of what researchers can study, and can be a powerful new approach to shed light on the mechanisms of renal epithelial regeneration. This protocol can be broadly applied to target cell populations in other organs in the zebrafish embryo to study injury and regeneration in any number of contexts of interest.

A day at the office (an advertorial).

This issue of General Dentistry highlights how tobacco products affect oral health. The following articles are presented to help general dentists with their efforts to champion cessation and to educate their patients. Please also note the guest editorial from Dr. Robert Mecklenburg. This first article by Dr. Stephen B. Corbin is an introduction to the topic at large and provides the reader with a suggested script for use in helping patients quit the smoking habit. We hope you find these articles useful and look forward to hearing your response. Please fax (312/440-4261) or e-mail (AGDJournal@agd.org) your thoughts on these articles. We hope these articles succeed in helping you help your patients beat the tobacco habit.

Low-frequency vibrations in alpha-helices: helicoidal analysis of polyalanine and deoxymyoglobin molecular dynamics trajectories.

We present an approach to the analysis of low-frequency (0-200 cm-1) alpha-helix vibrations in molecular dynamics simulations. The approach employs the P-Curves algorithm [H. Sklenar, C. Etchebest, and R. Lavery, (1989) Proteins: Structure, Function and Genetics, Vol. 6, pp. 46-60] to determine the helical axis and a set of helicoidal parameters describing the axis curvature and the position of the repeating units with respect to the axis and each other. The vibrations are analyzed in terms of time correlation functions of the fluctuations of P-Curves parameters and their Fourier transforms. Simulations of polyalanine and myoglobin are analyzed. For polyalanine, global twisting, bending, and stretching vibrations are found at 11, 20, and 40 cm-1, respectively. In myoglobin, the spectra of the global helix vibrations are qualitatively different from those of polyalanine and considerably more complicated. Local vibrations of individual amino acid units in the helix backbones are also analyzed with P-Curves and compared.

The absence of a m7G cap on beta-globin mRNA and alfalfa mosaic virus RNA 4 increases the amounts of initiation factor 4F required for translation.

beta-Globin mRNA and alfalfa mosaic virus (AMV) RNA 4, two naturally capped mRNAs, and satellite tobacco necrosis virus (STNV) RNA, a naturally uncapped mRNA, were prepared by in vitro transcription with and without a 5' m7G cap structure (m7G(5')ppp(5')N). The translation of the capped and uncapped forms of these mRNAs was measured in a crude S30 system and a partially purified system from wheat germ. In the S30 system the uncapped forms of beta-globin mRNA and AMV RNA 4 are much less active (greater than or equal to 10%) than their capped forms, whereas the uncapped and capped forms of STNV RNA are equally active. The low activity of uncapped beta-globin mRNA and AMV RNA 4 in the S30 system is due, in part, to inactivation of the uncapped mRNAs in this system. Additional studies, carried out in the partially purified system in which very little inactivation of the mRNAs occurs, show that the uncapped and capped forms of beta-globin mRNA or AMV RNA 4 differ markedly with respect to the amount of eukaryotic initiation factor (eIF)-4F required for translation. For beta-globin mRNA the absence of the 5' cap structure increases the concentration of eIF-4F required for half-maximal translation about 6-fold (from 10 to 60 nM) and for AMV RNA 4 it increases the concentration of eIF-4F about 12-fold (from 5 to 60 nM). The concentrations of eIF-3, eIF-4A, and eIF-4B required for half-maximal translation of the uncapped forms of beta-globin mRNA and AMV RNA 4 are either the same or only slightly higher (1.5- to 2-fold) than the concentrations required for the capped forms. With STNV RNA the concentration of eIF-4F required for half-maximal translation of either uncapped or capped STNV RNA is 3 nM, and the concentrations of eIF-3, eIF-4A, and eIF-4B required for the two forms are also the same. The translation of the capped and uncapped forms of beta-globin mRNA and AMV RNA 4 is inhibited strongly by low concentrations of m7GTP in the partially purified system containing low concentrations of eIF-4F. Under the same conditions, the translation of capped or uncapped STNV RNA is inhibited only slightly by m7GTP. These findings suggest the possibility that the mechanism by which eIF-4F interacts and initiates translation with naturally uncapped mRNAs may not be identical to the mechanism by which eIF-4F interacts and initiates translation of naturally capped mRNAs.

Applications of ultraviolet light in the preparation of platelet concentrates.

Passenger lymphocytes in platelet concentrates (PCs) may induce the formation of lymphocytotoxic antibodies (LCTAbs) and subsequent refractoriness to platelet transfusions. Ultraviolet (UV) irradiation can prevent lymphocytes' acting as stimulator or responder cells in mixed-lymphocyte reactions (MLRs) and could theoretically prevent LCTAb formation in vivo. A system has been devised for the delivery of UV irradiation to PCs; platelet storage characteristics and MLRs were evaluated in UV-irradiated PCs harvested from healthy donors with the Haemonetics V50 and PCS cell separators. MLR and response to phytohemagglutinin stimulation were abolished by a dose of 3000 joules per m2 at a mean wavelength of 310 nm. Platelet aggregatory responses to adenosine diphosphate (ADP), ristocetin, collagen and epinephrine, hypotonic shock response, and pH showed no important differences when control PCs and PCs irradiated as above were compared during 5 days of storage in Fenwal PL-1240 packs. Lactate production during storage was significantly higher in UV-treated PCs (p less than 0.001), but values did not exceed 20 mmol per L. UV transmission at 310 nm in standard blood product containers, including the Fenwal PL-146, PL-1240, and PL-732, was low (less than 30%), but it was acceptable in the Delmed Cryostorage and DuPont SteriCell packs (greater than 50%). UV irradiation may provide a simple and inexpensive means of producing nonimmunogenic PCs.

Conformation and pairing properties of the N-terminal fragments of trichorzianine and alamethicin: a theoretical study.

Energy optimizations are carried out on the N-terminal fragment of trichorzianine in comparison to that of alamethicin. The results indicate that the helical character of the (Ac...Pro13) sequence of trichorzianine (TA IIIc) is essentially alpha with a bend in the helix axis in the end proline region, a structure comparable to the optimal alpha-helical structure of the corresponding segment (Ac...Pro14) of alamethicin AI. However, two weak n----n + 3 interactions coexist in trichorzianine with the alpha-helical n----n + 4 hydrogen bonds. The possible role of the glutamine side-chains in pairing such segments together is considered.

Specificity in carcinogen-DNA interaction: a theoretical exploration of the factors involved in the effect of neighboring bases on N-methyl-N-nitrosourea alkylation of DNA.

Recent experimental studies indicate that in a polynucleotide chain neighboring bases have a significant effect on the relative alkylation of O6 or N7 of guanine by N-methyl-N-nitrosourea (MNU). This paper provides a theoretical exploration of this phenomenon in terms of an appropriate index of reactivity, called accessible surface integrated field (ASIF), introduced recently for the very sake of accounting for specificity or selectivity in drug-macromolecule interaction. The detailed analysis indicates that in the present case the observed variations in relative reactivity are attributable essentially to parallel variations in the accessibilities to the target atoms.