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Brachytherapy (BT) plays a key role in cancer treatment by delivering a high dose to a small volume over a short time. The use of BT is currently validated in a wide range of cancers such as cervical, prostate and breast cancers while being a favourable choice for organ preservation, such as in penile or rectal cancer, or in the setting of reirradiation. Consideration of the radiobiology of BT is integral to the choices made around dose and fractionation and combination with other techniques such as external beam radiotherapy (EBRT). Much of the radiobiology of brachytherapy is based on historic data, but fortunately there is a drive to integrate translational research including radiobiologic parameters into modern BT research. In a changing therapeutic landscape moving to a high dose rate (HDR) based on high dose per fraction, it is important to ensure that the incorporation of new radiobiology knowledge helps to drive clinical practice.This manuscript takes the ESTRO Brachytherapy pre-meeting course (May 3, 2024 - Glasgow ESTRO meeting) as a base and develops the concepts to present an overview of radiobiology in brachytherapy. Presented are 3 different considerations: the fundamentals of BT radiobiology (BT radiobiology history, biology and BT, α/β and re-irradiation), the pre-clinical radiobiology approach (pulsed dose radiotherapy (PDR) vs HDR, BT vs best EBRT techniques, high dose regions and integrated boost) and clinical radiobiology approaches (optimal number of BT fractions, radiobiology in BR for cervical, prostate, breast, skin/H&N and gastro-intestinal cancers). Presented is an analysis of radiobiology and modelling in BT aiding the integration of scientific pre-clinical and clinical data to allow a better understanding of the use of radioactive sources for cancer treatment.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment.Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

PURPOSE: With the growing popularity of badminton worldwide, the incidence of badminton-related ocular injuries is expected to rise. The high velocity of shuttlecocks renders ocular traumas particularly devastating, especially with the possibility of permanent vision loss. This study investigated the mechanism behind ocular complications through simulation analyses of mechanical stresses and pressures upon shuttlecock impact. DESIGN: Computational simulation study. PARTICIPANTS: None. METHODS: A 3-dimensional human eye model was reconstructed based on the physiological and biomechanical properties of various ocular tissues. Finite element analysis simulations involved a frontal collision with a shuttlecock projectile at 128.7 km/hour (80 mph). Intraocular pressure (IOP) changes and tissue stress were mapped and quantified in the following ocular structures: the limbus, ciliary body, zonular fibers, ora serrata, retina, and optic nerve head. MAIN OUTCOME MEASURES: Intraocular pressure and tissue stress. RESULTS: Upon shuttlecock impact, compressive force was transferred to the anterior pole of the cornea, propagating posteriorly to the optic nerve head. Deflection of forces anteriorly contributed to refractory oscillations of compressive and tensile stress of ocular tissue. Initial impact led to a momentary (

Individuals from Asian American (AA) and international Asian (IA) backgrounds are often lumped together in mental health research, which may obscure important differences in mental health presentation and need. While previous research has examined differences amongst AA and IA students seeking therapy at a single university counseling center, our study sought to better generalize these findings by utilizing a national data set to examine differences in treatment utilization, presenting concerns, overall distress, and improvement in treatment. Our results showed that IA students utilize therapy at lower rates than AA students. However, both groups attended appointments at roughly the same rate. Distress at intake was significantly higher for IA students across most domains measured. Finally, both groups improved in treatment at similar rates, with some differences observed between IA undergraduate and graduate students. We discuss implications for college counseling professionals and urge further research in this domain.

As the press for services at university counseling centers increases, so does the need to provide optimal therapeutic services. Ethnic glossing in previous research has combined rather disaggregated the mental health treatment experiences of American Latinx (AL) students and International Latinx (IL) students. The purpose of this paper was to examine potential differences in (1) the number of attended sessions, (2) symptom severity, and (3) treatment improvement rates. We used a nationwide dataset including 13,156 AL students and 911 IL students. Results indicated that (1) there was no significant difference in attendance rates, (2) AL students had significantly worse initial symptom severity (d = 0.24), and (3) there were no significant differences in improvement rates. We discuss the importance of understanding the different clinical presentations of AL and IL students, as well as the importance of addressing ethnic glossing in future research and clinical work.

Background: Cognitive communication disorder (CCD) following traumatic brain injury (TBI) is well documented and these communication problems impede successful re-integration into community living. While there is growing evidence for intervention to both detect and treat the impact of these deficits across the rehabilitation continuum, there are barriers to accessing services. Cognitive communication impairments may be missed because the person can talk, and this may mask the subtle but debilitating impact of a CCD. Referral to a speech and language therapist (SLT) may be overlooked or not timely, which prevents the individual accessing evidence-based interventions. Inadequate treatment provision and an under- or overestimation of communication capability can potentially undermine the effectiveness of wider team assessment and intervention. Aims: To report stakeholder views on specialist SLT input for CCD within a multidisciplinary team intervention for a community-dwelling individual with severe TBI. The investigation explored perspectives on understanding of CCD, on practice and on outcomes, in order to inform professional groups on perceived impacts of the evidence-to-practice gap. Methods and Procedures: A semi-structured interview methodology was employed with 11 stakeholder participants involved in a single case. Data were evaluated using a thematic framework method. Themes were inductively derived from the stakeholder narratives. Outcomes: Stakeholders reported the following outcomes from specialist SLT input for CCD within a collaborative team approach: improved engagement with rehabilitation and support teams, improved health-related quality of life and well-being, and increased client participation in community activities of personal relevance. Stakeholders also reported inequities in wider service provision where limitations in professional understanding of CCD and knowledge of best practice recommendations preclude access to specialist SLT services. Conclusions: CCDs are under-recognised and this can have a devastating effect on people with CCD and on those around them. Stakeholder reports provide evidence for the effectiveness of SLT practice recommendations for the treatment of CCD following TBI. They also provide additional evidence of persisting barriers to accessing treatment. Future research to explore ways to close this evidence-to-practice gap is required.

The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additional regulatory layers for VV-encoded synthetic transgene networks. The switches are applied to enable inducible expression of fusogenic proteins, dose-controlled delivery of toxic cytokines, and chemical regulation of VV replication. This toolbox enables the precise modulation of transgene circuitry in VV-vectored oncolytic virus design.

Deaf professionals, whom we term Deaf Language Specialists (DLS), are frequently employed to work with children and young people who have difficulties learning sign language, but there are few accounts of this work in the literature. Through questionnaires and focus groups, 23 DLSs described their work in this area. Deductive thematic analysis was used to identify how this compared to the work of professionals (typically Speech and Language Therapists/Pathologists, SLPs) working with hearing children with difficulties learning spoken language. Inductive thematic analysis resulted in the identification of two additional themes: while many practices by DLSs are similar to those of SLPs working with hearing children, a lack of training, information, and resources hampers their work; additionally, the cultural context of language and deafness makes this a complex and demanding area of work. These findings add to the limited literature on providing language interventions in the signed modality with clinical implications for meeting the needs of deaf and hard-of-hearing children who do not achieve expectations of learning a first language in their early years. The use of these initial results in two further study phases to co-deliver interventions and co-produce training for DLSs is briefly described.

University students frequently face significant distress. With increasing rates of students accessing University Counseling Center (UCC) services, it is critical for UCCs to provide targeted prevention and intervention efforts. However, researchers have conducted minimal research regarding the relationship of students' declared majors and mental health. Using archival data, this study investigated differences between students in different majors concerning: (1) rates of treatment utilization, (2) distress levels at the onset of treatment, and (3) rates of recovery while in treatment. A total of 21,514 participants were included. Results suggest significant differences by major in UCC utilization rates, distress levels at treatment onset, and recovery rates during treatment. While some previous studies have grouped "hard science" majors and "soft science" majors, we suggest that a more nuanced approach may help to better understand students' mental health needs. Implications for future research and recommendations for UCC intervention and prevention efforts are discussed.

BackgroundPrevious studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.MethodsIn this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I-III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype.FindingsWe analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20-80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0-186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41-1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79-2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p