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1.
J Med Imaging Radiat Sci ; 55(4): 101721, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39032240

RESUMEN

INTRODUCTION: The inter-fraction motion of pelvic ± para-aortic (PA) nodal volumes in prostate cancer patients with involved nodes is yet to be quantified and the optimal IGRT strategy for these patients is currently unknown. METHODS: A single-centre retrospective evaluation was performed investigating inter-fraction motion in the prostate and involved nodal volumes of patients receiving pelvic ± PA nodal irradiation. Patients were selected for inclusion if they; were undergoing prostate + pelvic node +/- PA node radiation for prostate cancer with involved lymph nodes and had received daily online CBCT scans. The planning CT and subsequent CBCT images from each treatment fraction were selected for analysis. RESULTS: Out of 567 CBCTs, from 20 patients, there were no incidences where independent lymph node displacement was >0.5 cm from planning volumes. Lymph node motion relative to prostate was >0.5 cm on 15 occasions out of 567 scans (2.6%). Where the difference between prostate and lymph nodes was >0.5 cm, this was always a result of the rectum causing variation in the prostate position, not a change in nodal position. DISCUSSION: These results suggests that there is limited independent displacement between the involved pelvic ± PA nodal volumes and bony anatomy. Therefore, bony anatomy could be used as a lymph node match surrogate for prostate patients receiving nodal irradiation for active disease. The results also suggest additional emphasis should be placed on bowel preparation in these patients to reduce the risk of geographical miss. CONCLUSION: In conclusion, the results of this evaluation suggests that there is limited independent displacement between the involved pelvic ± PA nodal volumes and bony anatomy. This provides evidence to trials investigating the role of pelvic ± PA nodal irradiation to ensure appropriate margins and IGRT strategies are used when investigating this further.

2.
Radiother Oncol ; : 110581, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39395670

RESUMEN

BACKGROUND AND PURPOSE: Reducing motion is vital in treating hepatobiliary (HPB) and pancreatic malignancies. Abdominal compression (AC) and breath-hold (BH) techniques aim to minimise respiratory motion, yet their adoption remains limited, and practices vary. This review examines the impact of AC and BH on motion, set-up errors, and patient tolerability in HPB and pancreatic patients. MATERIALS AND METHODS: This systematic review, conducted using PRISMA and PICOS criteria, includes publications from January 2015 to February 2023. Eligible studies focused on AC and BH interventions in adults with HPB and pancreatic malignancies. Endpoints examined motion, set-up errors, intra-fraction errors, and patient tolerability. Due to study heterogeneity, Synthesis Without Meta-Analysis was used, and a 5 mm threshold assessed the impact of motion mitigation. RESULTS: In forty studies, 14 explored AC and 26 BH, with 20 on HPB, 13 on pancreatic, and 7 on mixed cohorts. Six studied pre-treatment, 22 inter/intra-fraction errors, and 12 both. Six AC pre-treatment studies showed > 5 mm motion, and 4 BH and 2 AC studies reported > 5 mm inter-fraction errors. Compression studies commonly investigated the arch and belt, and DIBH was the predominant BH technique. No studies compared AC and BH. There was variation in the techniques, and several studies did not follow standardised error reporting. Patient experience and tolerability were under-reported. CONCLUSION: The results indicate that AC effectively reduces motion, but its effectiveness may vary. BH can immobilise motion; however, it can be inconsistent between fractions. The review underscores the need for larger, standardised studies and emphasizes the importance of considering the patient's perspective for tailored treatments.

3.
Radiother Oncol ; 199: 110460, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39069085

RESUMEN

BACKGROUND AND PURPOSE: Radiotherapy trial quality assurance (RT QA) is crucial for ensuring the safe and reliable delivery of radiotherapy trials, and minimizing inter-institutional variations. While previous studies focused on outlining and planning quality assurance (QA), this work explores the process of Image-Guided Radiotherapy (IGRT), and adaptive radiotherapy. This study presents findings from during-accrual QA in the RAIDER trial, evaluating concordance between online and offline plan selections for bladder cancer participants undergoing adaptive radiotherapy. RAIDER had two seamless stages; stage 1 assessed adherence to dose constraints of dose escalated radiotherapy (DART) and stage 2 assessed safety. The RT QA programme was updated from stage 1 to stage 2. MATERIALS AND METHODS: Data from all participants in the adaptive arms (standard dose adaptive radiotherapy (SART) and DART) of the trial was requested (33 centres across the UK, Australia and New Zealand). Data collection spanned September 2015 to December 2022 and included the plans selected online, on Cone-Beam Computed Tomography (CBCT) data. Concordance with the plans selected offline by the independent RT QA central reviewer was evaluated. RESULTS: Analysable data was received for 72 participants, giving a total of 884 CBCTs. The overall concordance rate was 83% (723/884). From stage 1 to stage 2 the concordance in the plans selected improved from 75% (369/495) to 91% (354/389). CONCLUSION: During-accrual IGRT QA positively influenced plan selection concordance, highlighting the need for ongoing support when introducing a new technique. Overall, it contributes to advancing the understanding and implementation of QA measures in adaptive radiotherapy trials.


Asunto(s)
Garantía de la Calidad de Atención de Salud , Planificación de la Radioterapia Asistida por Computador , Radioterapia Guiada por Imagen , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/radioterapia , Radioterapia Guiada por Imagen/métodos , Radioterapia Guiada por Imagen/normas , Planificación de la Radioterapia Asistida por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/normas , Dosificación Radioterapéutica , Nueva Zelanda , Australia , Radioterapia de Intensidad Modulada/métodos , Radioterapia de Intensidad Modulada/normas , Tomografía Computarizada de Haz Cónico , Femenino
4.
Radiother Oncol ; 195: 110226, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38492670

RESUMEN

The European SocieTy for Radiotherapy and Oncology (ESTRO) organized a one-year pilot mentoring programme. At evaluation after one year, both mentors and mentees scored the programme with a median score of 9 on a scale of 10. All of the mentors indicated that they wanted to participate again as mentors.


Asunto(s)
Tutoría , Oncología por Radiación , Sociedades Médicas , Humanos , Proyectos Piloto , Oncología por Radiación/educación , Europa (Continente) , Oncología Médica/educación , Mentores , Evaluación de Programas y Proyectos de Salud
5.
Eur Urol ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39379236

RESUMEN

BACKGROUND AND OBJECTIVE: Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule. METHODS: RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART. KEY FINDINGS AND LIMITATIONS: A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy. CONCLUSIONS AND CLINICAL IMPLICATIONS: Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts.

6.
J Intellect Dev Disabil ; 38(1): 1-11, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23181349

RESUMEN

BACKGROUND: One of the most commonly cited rationales for inclusive education is to enable the development of quality relationships with typically developing peers. Relatively few researchers have examined the features of the range of relationships that children with developmental disability form in inclusive school settings. METHOD: Interviews were conducted with 25 children with developmental disability, aged 5 and 12 years, their 3 closest peers, and parents and teachers to examine 6 types of relationships. RESULTS: Behaviours associated with general friendship and acquaintance were the most commonly reported. Few dyads reported high rates of behaviour associated with special treatment, helping, ignoring, or intimate best friend relationships. CONCLUSIONS: The relationships of the majority of dyads were characterised by friendship or acceptance, but evidence of more intimate relationships was limited. An important direction for future research is the examination of ways to encourage more intimate relationships.


Asunto(s)
Discapacidades del Desarrollo/psicología , Amigos , Relaciones Interpersonales , Grupo Paritario , Australia , Niño , Preescolar , Femenino , Humanos , Entrevistas como Asunto , Integración Escolar , Masculino , Instituciones Académicas , Conducta Social , Encuestas y Cuestionarios
7.
Br J Radiol ; 95(1140): 20220749, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36314737

RESUMEN

The ability to request clinical imaging is included in many advanced roles of health-care professionals in the UK and is seen as a useful component in ensuring patients receive the right care, by the right person, at the right time. In order that diagnostic imaging referrals are appropriate, timely and safely made, the British Institute of Radiology has produced a position statement on the governance requirements covering clinical imaging requests from non-medical referrers (NMRs). This document is intended to help define the role of a NMR and to ensure they are practising responsibly and safely, within professional and legal frameworks, as part of the wider interprofessional team.


Asunto(s)
Radiología , Humanos , Radiografía , Derivación y Consulta
8.
Res Dev Disabil ; 128: 104301, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35797777

RESUMEN

BACKGROUND: Despite awareness of the need to support autistic students in transitions, great variability is found in transition supports provided across different school environments and staff within schools. Moreover, strategies implemented may not provide autistic students with the supports they need to reduce their anxiety and build their sense of self-determination during transitions. AIM: The current paper aimed to determine what types of transition supports are employed in Australian schools to support autistic students and to consider these supports through the lens of self-determination theory. METHODS: Surveys were conducted with 422 parents, educators and education specialists who provided information on transition supports employed in schools in open-ended questions. Transition supports were explored in more depth through interviews with a subset of 30 participants. RESULTS: Findings indicate that schools provided a range of strategies, programmes and planning processes to support students in transitions. However, students were often passive recipients of supports who were rarely involved in the planning and implementation of strategies. CONCLUSION: The results of this study suggest that current transition supports implemented in schools may support autistic students in some transitions, but are not likely to develop their self-determination to successfully navigate transitions over the long-term. WHAT THIS PAPER ADDS?: Drawing on self-determination theory, this study provides a unique and much needed examination of the types of strategies employed in schools and offers a critical reflection as to whether these strategies are likely to support autistic students to develop a sense of autonomy, competence and relatedness to successfully manage future transitions.


Asunto(s)
Trastorno Autístico , Australia , Humanos , Autonomía Personal , Instituciones Académicas , Estudiantes
9.
J Autism Dev Disord ; 52(3): 1268-1282, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33909209

RESUMEN

Students with autism often show challenges in social communication, particularly in initiating and responding behaviors. While the classroom offers a natural context for peer interactions, few interventions are designed specifically for classroom settings. This study investigated the effects of a classroom-teacher implemented social communication intervention, known as Social Stations, on the initiating and responding behaviors of students with autism. The study was set in an inclusive primary school, with the teacher embedding the intervention into the student's daily literacy lessons. All students with autism showed significant improvements in the targeted behaviors, with improvements maintained over time. This study suggests that social communication interventions can be implemented by teachers as part of a daily classroom program.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Trastorno Autístico/terapia , Comunicación , Humanos , Maestros , Instituciones Académicas , Estudiantes
10.
Artículo en Inglés | MEDLINE | ID: mdl-35450274

RESUMEN

Deep inspiration breath-hold (DIBH) is an advanced radiotherapy technique that has been shown to have dosimetric benefits in the treatment of patients with mediastinal lymphoma. Whilst there is much published data on the use of DIBH in breast radiotherapy, reports on the use of the technique in mediastinal lymphoma patients remain limited. As the first NHS centre in the UK to implement DIBH in this pt group, we have evaluated our experience and success in using this technique over a 5 year period.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35434387

RESUMEN

Deep inspiration breath-hold, butterfly volumetric modulated arc therapy and daily imaging techniques for mediastinal lymphoma patients have been introduced in a single department. Whilst introducing these techniques, there were many practical lessons to be learned across the patient pathway, from pre-treatment through to treatment delivery.Therapeutic radiographers were key members of the multi-disciplinary team implementing these techniques. This work reflects on the experience of introducing these advanced techniques for mediastinal lymphoma patients and the lessons learnt.

12.
Br J Radiol ; 95(1139): 20220070, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36000497

RESUMEN

OBJECTIVES: Cone-beam computed tomography (CBCT) for radiotherapy treatment verification has increased in frequency; therefore, it is crucial to optimise image quality and radiation dose to patients. The aim of this study was to implement optimised CBCT protocols for the Varian TrueBeams for most tumour sites in adult patients. METHODS: A combination of patient size-specific CBCT protocols from the literature and developed in-house was used. Scans taken before and after optimisation were compared by senior radiographers and physicists to evaluate how changes affected image quality and clinical usability for online image registration. The change in dose for each new CBCT protocol was compared to the Varian default. A clinical audit was performed following implementation to evaluate the changes in imaging dose for all patients receiving a CBCT during that period. RESULTS: Ten CBCT protocols were introduced including head and neck and patient-size-specific thorax and pelvis/abdomen protocols. Scans from 102 patients with images before and after optimisation were assessed, none of the scans showed image quality changes compromising clinical usability and for some image quality was improved. Between November 2020 and June 2021, 1185 patients had CBCTs using the new protocols. The imaging dose was reduced for 52% of patients, remained the same for 37% and increased for 12%. CONCLUSIONS: This study showed that substantial dose reductions and image quality improvements can be achieved with simple changes in the default settings of the Varian TrueBeam CBCT without affecting the radiographers' confidence in online image registration. ADVANCES IN KNOWLEDGE: This study represents a comprehensive assessment and optimisation of CBCT protocols for most sites, validated on a large cohort of patients.


Asunto(s)
Tomografía Computarizada de Haz Cónico Espiral , Humanos , Fantasmas de Imagen , Tomografía Computarizada de Haz Cónico/métodos , Pelvis , Cabeza
13.
Artículo en Inglés | MEDLINE | ID: mdl-35198744

RESUMEN

Two multicentre adaptive radiotherapy trials utilising Plan of the Day (PoD) with a library of plans were introduced in 35 centres. The common issues that arose from all centres when introducing PoD were collated retrospectively, through reviewing the data pertaining to the pre-trial and on-trial quality assurance programme. It was found that 1,295 issues arose when introducing PoD in outlining, planning, treatment delivery i.e., PoD selection, and in the overall process of delivering PoD. There was no difference in the number of issues that arose from pre-trial to on-trial. Thus, it is recommended that the implementation of PoD is supported by guidance, reviews, and continuous monitoring.

14.
BMJ Open ; 12(8): e061002, 2022 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-36041760

RESUMEN

INTRODUCTION: Continuity of child and family healthcare is vital for optimal child health and development for developmentally vulnerable children. Migrant and refugee communities are often at-risk of poor health outcomes, facing barriers to health service attendance including cultural, language, limited health literacy, discrimination and unmet psychosocial needs. 'Integrated health-social care hubs' are physical hubs where health and social services are co-located, with shared referral pathways and care navigation. AIM: Our study will evaluate the impact, implementation and cost-benefit of the First 2000 Days Care Connect (FDCC) integrated hub model for pregnant migrant and refugee women and their infants. MATERIALS AND METHODS: This study has three components. Component 1 is a non-randomised controlled trial to compare the FDCC model of care with usual care. This trial will allocate eligible women to intervention and control groups based on their proximity to the Hub sites. Outcome measures include: the proportion of children attending child and family health (CFH) nurse services and completing their CFH checks to 12 months of age; improved surveillance of growth and development in children up to 12 months, post partum; improved breastfeeding rates; reduced emergency department presentations; and improved maternal well-being. These will be measured using linked medical record data and surveys. Component 2 will involve a mixed-method implementation evaluation to clarify how and why FDCC was implemented within the sites to inform future roll-out. Component 3 is a within-trial economic evaluation from a healthcare perspective to assess the cost-effectiveness of the Hubs relative to usual care and the implementation costs if Hubs were scaled and replicated. ETHICS AND DISSEMINATION: Ethical approval was granted by the South Eastern Sydney Local Health District Human Research Ethics Committee in July 2021 (Project ID: 020/ETH03295). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ACTRN12621001088831.


Asunto(s)
Servicios de Salud del Niño , Refugiados , Migrantes , Niño , Análisis Costo-Beneficio , Salud de la Familia , Femenino , Humanos , Lactante , Embarazo
15.
BMJ Open ; 12(4): e049119, 2022 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-35487526

RESUMEN

INTRODUCTION: The standard of care for patients with localised rectal cancer is radical surgery, often combined with preoperative neoadjuvant (chemo)radiotherapy. While oncologically effective, this treatment strategy is associated with operative mortality risks, significant morbidity and stoma formation. An alternative approach is chemoradiotherapy to try to achieve a sustained clinical complete response (cCR). This non-surgical management can be attractive, particularly for patients at high risk of surgical complications. Modern radiotherapy techniques allow increased treatment conformality, enabling increased radiation dose to the tumour while reducing dose to normal tissue. The objective of this trial is to assess if radiotherapy dose escalation increases the cCR rate, with acceptable toxicity, for treatment of patients with early rectal cancer unsuitable for radical surgery. METHODS AND ANALYSIS: APHRODITE (A Phase II trial of Higher RadiOtherapy Dose In The Eradication of early rectal cancer) is a multicentre, open-label randomised controlled phase II trial aiming to recruit 104 participants from 10 to 12 UK sites. Participants will be allocated with a 2:1 ratio of intervention:control. The intervention is escalated dose radiotherapy (62 Gy to primary tumour, 50.4 Gy to surrounding mesorectum in 28 fractions) using simultaneous integrated boost. The control arm will receive 50.4 Gy to the primary tumour and surrounding mesorectum. Both arms will use intensity-modulated radiotherapy and daily image guidance, combined with concurrent chemotherapy (capecitabine, 5-fluorouracil/leucovorin or omitted). The primary endpoint is the proportion of participants with cCR at 6 months after start of treatment. Secondary outcomes include early and late toxicities, time to stoma formation, overall survival and patient-reported outcomes (European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires QLQ-C30 and QLQ-CR29, low anterior resection syndrome (LARS) questionnaire). ETHICS AND DISSEMINATION: The trial obtained ethical approval from North West Greater Manchester East Research Ethics Committee (reference number 19/NW/0565) and is funded by Yorkshire Cancer Research. The final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines. TRIAL REGISTRATION NUMBER: ISRCTN16158514.


Asunto(s)
Neoplasias del Recto , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Ensayos Clínicos Fase II como Asunto , Humanos , Estudios Multicéntricos como Asunto , Complicaciones Posoperatorias , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/radioterapia , Síndrome
16.
Autism Dev Lang Impair ; 5: 2396941520945522, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-36381554

RESUMEN

Background: Studies involving autistic adults have often focused on negative outcomes and quality of life ratings. Aims: This study provides a different viewpoint by examining the perspectives of autistic men who consider themselves to be successful. Methods: Data were gathered from 10 men who shared their experiences and perceptions regarding their journey to achieve success. Self-determination theory provided a useful lens for examining the men's narratives and understanding the factors that led to their success. Results: Analysis of interviews revealed four main themes: (1) being my own self, (2) a competent professional, (3) solving problems in a neurotypical world, and (4) relating and connecting. These themes reflect the men's perception of their own self-determination including their autonomy, competence, and relatedness with others. Conclusions: The men's sense of success was derived from their ability to achieve competence in their work, act without help or influence from others and demonstrate a high level of self-awareness and self-reflection. Despite this, many continued to experience difficulty in the social areas of their lives.Implications: These findings suggest that self-determination theory may present an alternative and more positive means of enacting support programs for autistic individuals, and males in particular.

17.
BMJ Open ; 10(5): e037134, 2020 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-32461298

RESUMEN

INTRODUCTION: Patients with muscle invasive bladder cancer (MIBC) who are unfit and unsuitable for standard radical treatment with cystectomy or daily radiotherapy present a large unmet clinical need. Untreated, they suffer high cancer specific mortality and risk significant disease-related local symptoms. Hypofractionated radiotherapy (delivering higher doses in fewer fractions/visits) is a potential treatment solution but could be compromised by the mobile nature of the bladder, resulting in target misses in a significant proportion of fractions. Adaptive 'plan of the day' image-guided radiotherapy delivery may improve the precision and accuracy of treatment. We aim to demonstrate within a randomised multicentre phase II trial feasibility of plan of the day hypofractionated bladder radiotherapy delivery with acceptable rates of toxicity. METHODS AND ANALYSIS: Patients with T2-T4aN0M0 MIBC receiving 36 Gy in 6-weekly fractions are randomised (1:1) between treatment delivered using a single-standard plan or adaptive radiotherapy using a library of three plans (small, medium and large). A cone beam CT taken prior to each treatment is used to visualise the anatomy and select the most appropriate plan depending on the bladder shape and size. A comprehensive radiotherapy quality assurance programme has been instituted to ensure standardisation of radiotherapy planning and delivery. The primary endpoint is to exclude >30% acute grade >3 non-genitourinary toxicity at 3 months for adaptive radiotherapy in patients who received >1 fraction (p0=0.7, p1=0.9, α=0.05, ß=0.2). Secondary endpoints include local disease control, symptom control, late toxicity, overall survival, patient-reported outcomes and proportion of fractions benefiting from adaptive planning. Target recruitment is 62 patients. ETHICS AND DISSEMINATION: The trial is approved by the London-Surrey Borders Research Ethics Committee (13/LO/1350). The results will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. TRIAL REGISTRATION NUMBER: NCT01810757.


Asunto(s)
Radioterapia Guiada por Imagen , Radioterapia de Intensidad Modulada , Neoplasias de la Vejiga Urinaria , Ensayos Clínicos Fase II como Asunto , Cistectomía , Humanos , Londres , Estudios Multicéntricos como Asunto , Radioterapia de Intensidad Modulada/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/cirugía
18.
Elife ; 92020 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-32096469

RESUMEN

In the nematode C. elegans, insulin signaling regulates development and aging in response to the secretion of numerous insulin peptides. Here, we describe a novel, non-signaling isoform of the nematode insulin receptor (IR), DAF-2B, that modulates insulin signaling by sequestration of insulin peptides. DAF-2B arises via alternative splicing and retains the extracellular ligand binding domain but lacks the intracellular signaling domain. A daf-2b splicing reporter revealed active regulation of this transcript through development, particularly in the dauer larva, a diapause stage associated with longevity. CRISPR knock-in of mScarlet into the daf-2b genomic locus confirmed that DAF-2B is expressed in vivo and is likely secreted. Genetic studies indicate that DAF-2B influences dauer entry, dauer recovery and adult lifespan by altering insulin sensitivity according to the prevailing insulin milieu. Thus, in C. elegans alternative splicing at the daf-2 locus generates a truncated IR that fine-tunes insulin signaling in response to the environment.


Asunto(s)
Empalme Alternativo , Caenorhabditis elegans/metabolismo , Insulina/metabolismo , Receptor de Insulina/genética , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Genes de Helminto , Insulina/química , Mutación , Transducción de Señal
19.
BMJ Open ; 10(12): e041005, 2020 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-33384390

RESUMEN

INTRODUCTION: Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity. METHODS AND ANALYSIS: Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes. ETHICS AND DISSEMINATION: This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. TRIAL REGISTRATION NUMBER: NCT02447549; Pre-results.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Cistectomía , Fraccionamiento de la Dosis de Radiación , Humanos , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/radioterapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/cirugía
20.
Autism ; 23(2): 274-286, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29382208

RESUMEN

Initiating and responding to peers are social communication behaviors which are challenging for students with autism. We reviewed intervention studies set in mainstream elementary schools, which targeted these behaviors and reported on intervention outcomes as well as the resources required for their implementation. A total of 22 studies met the criteria for inclusion. Findings suggest that school-based interventions can increase the frequency and duration of initiating and responding behaviors in elementary school aged students with autism. These interventions were resource-intensive and usually delivered by researchers or teaching assistants away from the classroom. Future research should build on this emerging evidence base to consider interventions which could be implemented by classroom teachers as part of the classroom program.


Asunto(s)
Trastorno Autístico/rehabilitación , Comunicación , Integración Escolar , Servicios de Salud Mental Escolar , Conducta Social , Trastorno del Espectro Autista/rehabilitación , Niño , Humanos
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