Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial.

PURPOSE: Dose-escalated radiation therapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiation therapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease while limiting toxicity. This study evaluated the toxicity and quality of life (QoL) with CyberKnife-based SBRT and simultaneous integrated boost in localized prostate cancer. METHODS AND MATERIALS: Eligible participants included newly diagnosed, biopsy-proven unfavorable intermediate- to high-risk localized prostate cancer (at least 1 of the following: Gleason ≥4+3, magnetic resonance imaging(MRI)-defined T3a N0, prostate-specific antigen ≥20) with up to 2 MRI-identified DILs. Participants received 36.25 Gy in 5 fractions on alternative days with a simultaneous boost to DIL up to 47.5 Gy as allowed by organ-at-risk constraints delivered by CyberKnife. All participants received androgen deprivation therapy. The primary outcome measure was acute grade 2+ genitourinary toxicity. Acute and late genitourinary and gastrointestinal toxicity using Radiation Therapy Oncology Group scoring, biochemical parameters, International Prostate Symptom Score, International Index of Erectile Function 5, and EQ-5D QoL outcomes were assessed. RESULTS: Between 2013 and 2023, 20 participants were enrolled with a median follow-up of 30 months. The median D95 dose to DIL was 47.43 Gy. Cumulative acute grade 2+ genitourinary and gastrointestinal toxicity were 25% and 30%, respectively. One patient developed acute grade 3 genitourinary toxicity (5%). There is no late grade 3 genitourinary or gastrointestinal toxicity to date. International Prostate Symptom Score and urinary QoL scores recovered to baseline by 6 months. Patient-reported outcomes showed no significant change in EQ-5D QoL scores at 12 weeks and 1 year. There are no cases of biochemical relapse reported to date. CONCLUSIONS: CyberKnife SBRT-delivered dose of 36.25 Gy to the prostate with a simultaneous integrated boost up to 47.5 Gy is well tolerated. Acute and late genitourinary and gastrointestinal toxicity rates are comparable to other contemporary SBRT trials and series with focal boost.

Evaluation of PTV margins and plan robustness for single isocentre multiple target stereotactic radiosurgery.

PURPOSE: Robustness to residual setup errors and linac delivery errors of BrainLab Elements single-isocentre-multiple-target stereotactic radiosurgery was evaluated. METHODS: Residual setup errors of 13 patients were evaluated. Linac delivery error was quantified through multi-metastases-Winston-Lutz measurements. PTV margins were calculated using the van Herk recipe. Patient scans were translated and rotated by the median and 95th percentile of the combined uncertainties, and plans were recalculated subsequently. Previous patients' plans were then replanned with the derived margins, effects on GTV coverage and normal brain doses were assessed. RESULTS: Mean (±stdev) coverage of all targets in the original plans were 99.4% (±0.9%) and 98.9% (±1.0%) for 1 and 3-fraction patients respectively. Median geometrical errors did not result in significant differences. A statistically significant reduction in coverage to 91.4% (±10.4%) and 93.0% (±9.6%) was seen under 95th percentile errors. Applying the derived optimal margin of 0.5 mm resulted in 78% of the GTVs retaining a coverage of 98% or above even in the presence of 95th percentile errors, compared to only 30% if no margins were applied. Replanning with margins also caused no significant increase to local normal brain doses, however global dose increases varied according to the number of metastases. CONCLUSIONS: Plans were shown to be robust to average geometrical uncertainties despite targets having no margins, however occurrence of GTV under-coverage increased under 95th percentile scenarios. The margin was proven to substantially improve the target dose coverage with limited change to local normal brain doses, although not all sources of geometrical uncertainty were considered.

Drinking water quality management progress in Ontario, two decades after Walkerton.

Following the waterborne disease outbreak in Walkerton, Ontario, the province made significant efforts to implement recommendations of the public inquiry that resulted. As Ontario reformed its drinking water sector, other jurisdictions were advancing risk-based quality management frameworks for drinking water, including the World Health Organization (WHO) through its water safety plan (WSP) framework. Two decades after the Walkerton tragedy, this paper seeks to: (i) evaluate alignment of Ontario's Drinking Water Quality Management Standard (DWQMS) with the WSP framework (ii) review readily available data for evidence that Ontario's DWQMS implementation has improved drinking water safety and promoted a preventive approach through risk-based quality management. Our study found strong alignment between the Ontario DWQMS and WSP frameworks, with supporting programmes and risk assessment procedures present. Analysis of available regulatory data revealed abundant reporting of water quality and adverse incidents in municipal water systems. However, performance data were publicly available, the use of percentage scores for water quality testing obscures the details of system performance and water safety. Reports describing the DWQMS plan and audit results were difficult to obtain and not standardized. There is a need to develop mechanisms to ensure continual improvement of the DWQMS.

Congenital and Neoplastic Cranial Deformities in Wild Giraffe (Giraffa spp.).

Congenital deformities and neoplasia are poorly documented in wildlife, owing to the difficulty of detection in wild populations. Congenital deformities may lead to premature mortality, thus reducing the chances of thorough documentation. Importantly, neoplasia diagnoses depend on either sampling suspicious lesions from living individuals or access to fresh, undisturbed carcasses, which can prove challenging. We describe five cases of suspected congenital cranial deformities (midfacial cleft, wry nose, and brachygnathia inferior) and two possible cases of cranial neoplasia (orbital bone mass and a soft tissue mass) opportunistically observed in wild giraffe (Giraffa spp.) across their range in Africa. Although cases are largely limited to subjective description because physical examination is often not possible, it is critical to document such observations to help identify and track potential health concerns in wild giraffe populations.

Inactivation of biofilm-bound bacterial cells using irradiation across UVC wavelengths.

Opportunistic pathogens (OPs), such as Pseudomonas spp., Legionella spp., and mycobacteria, have been detected in biofilms in drinking water distribution systems and water storage tanks and pose potential risks to finished drinking water quality and safety. Emerging UV technologies, such as UV light emitting diodes (LEDs) and krypton chloride (KrCl*) excimers, could provide an alternative to chemical-based secondary disinfection (i.e., chlorine or chloramines) for controlling biofilm-bound OPs. UV systems offer long lifetimes, ability to select wavelength, small size with high power density, and limited-to-no disinfection by-product formation. In this study, inactivation of biofilm-bound Pseudomonas aeruginosa cells across different maturities was investigated using five UVC devices with different peak emission wavelengths, including a KrCl* excimer (222 nm), a low pressure mercury vapor lamp (254 nm), and three UV LEDs (260 nm, 270 nm, and 282 nm). The UV transmittance and absorbance through the biofilm structure was also documented for the first time using a unique approach. Our results show all UVC devices can inactivate biofilm-bound P. aeruginosa cells up to a point, among which the UV LED with peak emission at 270 nm provided the best disinfection performance. UV sensitivities of biofilm-bound cells decreased with biofilm maturity and while initial rates of inactivation were high, no more than 1.5-2.5 log reduction was possible. Re-suspended biofilm bacteria in aqueous solution were highly sensitive to UV, reaching greater than 6 log reduction. UV shielding by biofilm constituents was observed and was likely one of the reasons for UV resistance but did not fully explain the difference in UV sensitivity between biofilm-bound cells versus planktonic cells. This study improves upon fundamental knowledge and provides guidance for innovative designs using emerging UV technologies for biofilm and pathogen control in water distribution systems.

Skeletal dysplasia-like syndromes in wild giraffe.

OBJECTIVE: Skeletal dysplasias, cartilaginous or skeletal disorders that sometimes result in abnormal bone development, are seldom reported in free-ranging wild animals. Here, we use photogrammetry and comparative morphometric analyses to describe cases of abnormal appendicular skeletal proportions of free-ranging giraffe in two geographically distinct taxa: a Nubian giraffe (Giraffa camelopardalis camelopardalis) in Murchison Falls National Park, Uganda and an Angolan giraffe (Giraffa giraffa angolensis) on a private farm in central Namibia. RESULTS: These giraffe exhibited extremely shortened radius and metacarpal bones relative to other similarly aged giraffe. Both giraffe survived to at least subadult life stage. This report documents rare occurrences of these apparent skeletal dysplasias in free-ranging wild animals and the first records in giraffe.

Reach, Recruitment, Dose, and Intervention Fidelity of the GoActive School-Based Physical Activity Intervention in the UK: A Mixed-Methods Process Evaluation.

School-based multi-component physical activity (PA) promotion is advocated; however, research has indicated that a multi-component approach may not always be effective at increasing adolescent PA. Evaluation of the GoActive 12-week multi-component school-based intervention showed no effect on adolescent PA. A mixed-methods process evaluation was embedded to facilitate greater understanding of the results, to elicit subgroup perceptions, and to provide insight into contextual factors influencing intervention implementation. This paper presents the reach, recruitment, dose, and fidelity of GoActive, and identifies challenges to implementation. The process evaluation employed questionnaires (1543 Year 9s), individual interviews (16 Year 9s; 7 facilitators; 9 contact teachers), focus groups (48 Year 9s; 58 mentors), alongside GoActive website analytics and researcher observations. GoActive sessions reached 39.4% of Year 9s. Intervention satisfaction was relatively high for mentors (87.3%) and facilitators (85.7%), but lower for Year 9s (59.5%) and teachers (50%). Intervention fidelity was mixed within and between schools. Mentorship was the most implemented component. Factors potentially contributing to low implementation included ambiguity of the roles subgroups played within intervention delivery, Year 9 engagement, institutional support, and further school-level constraints. Multiple challenges and varying contextual considerations hindered the implementation of GoActive in multiple school sites. Methods to overcome contextual challenges to implementation warrant in-depth consideration and innovative approaches.

Effectiveness and cost-effectiveness of the GoActive intervention to increase physical activity among UK adolescents: A cluster randomised controlled trial.

BACKGROUND: Less than 20% of adolescents globally meet recommended levels of physical activity, and not meeting these recommended levels is associated with social disadvantage and rising disease risk. The determinants of physical activity in adolescents are multilevel and poorly understood, but the school's social environment likely plays an important role. We conducted a cluster randomised controlled trial to assess the effectiveness of a school-based programme (GoActive) to increase moderate-to-vigorous physical activity (MVPA) among adolescents. METHODS AND FINDINGS: Non-fee-paying, co-educational schools including Year 9 students in the UK counties of Cambridgeshire and Essex were eligible for inclusion. Within participating schools (n = 16), all Year 9 students were eligible and invited to participate. Participants were 2,862 13- to 14-year-olds (84% of eligible students). After baseline assessment, schools were computer-randomised, stratified by school-level pupil premium funding (below/above county-specific median) and county (control: 8 schools, 1,319 participants, mean [SD] participants per school n = 165 [62]; intervention: 8 schools, 1,543 participants, n = 193 [43]). Measurement staff were blinded to allocation. The iteratively developed, feasibility-tested 12-week intervention, aligned with self-determination theory, trained older adolescent mentors and in-class peer-leaders to encourage classes to conduct 2 new weekly activities. Students and classes gained points and rewards for engaging in any activity in or out of school. The primary outcome was average daily minutes of accelerometer-assessed MVPA at 10-month follow-up; a mixed-methods process evaluation evaluated implementation. Of 2,862 recruited participants (52.1% male), 2,167 (76%) attended 10-month follow-up measurements; we analysed the primary outcome for 1,874 participants (65.5%). At 10 months, there was a mean (SD) decrease in MVPA of 8.3 (19.3) minutes in the control group and 10.4 (22.7) minutes in the intervention group (baseline-adjusted difference [95% confidence interval] -1.91 minutes [-5.53 to 1.70], p = 0.316). The programme cost £13 per student compared with control; it was not cost-effective. Overall, 62.9% of students and 87.3% of mentors reported that GoActive was fun. Teachers and mentors commented that their roles in programme delivery were unclear. Implementation fidelity was low. The main methodological limitation of this study was the relatively affluent and ethnically homogeneous sample. CONCLUSIONS: In this study, we observed that a rigorously developed school-based intervention was no more effective than standard school practice at preventing declines in adolescent physical activity. Interdisciplinary research is required to understand educational-setting-specific implementation challenges. School leaders and authorities should be realistic about expectations of the effect of school-based physical activity promotion strategies implemented at scale. TRIAL REGISTRATION: ISRCTN Registry ISRCTN31583496.

Clinical and cost-effectiveness of a diabetes education and behavioural weight management programme versus a diabetes education programme in adults with a recent diagnosis of type 2 diabetes: study protocol for the Glucose Lowering through Weight management (GLoW) randomised controlled trial.

INTRODUCTION: People with type 2 diabetes (T2D) can improve glycaemic control or even achieve remission through weight loss and reduce their use of medication and risk of cardiovascular disease. The Glucose Lowering through Weight management (GLoW) trial will evaluate whether a tailored diabetes education and behavioural weight management programme (DEW) is more effective and cost-effective than a diabetes education (DE) programme in helping people with overweight or obesity and a recent diagnosis of T2D to lower their blood glucose, lose weight and improve other markers of cardiovascular risk. METHODS AND ANALYSIS: This study is a pragmatic, randomised, single-blind, parallel group, two-arm, superiority trial. We will recruit 576 adults with body mass index>25 kg/m2 and diagnosis of T2D in the past 3 years and randomise them to a tailored DEW or a DE programme. Participants will attend measurement appointments at a local general practitioner practice or research centre at baseline, 6 and 12 months. The primary outcome is 12-month change in glycated haemoglobin. The effect of the intervention on the primary outcome will be estimated and tested using a linear regression model (analysis of covariance) including randomisation group and adjusted for baseline value of the outcome and the randomisation stratifiers. Participants will be included in the group to which they were randomised, under the intention-to-treat principle. Secondary outcomes include 6-month and 12-month changes in body weight, body fat percentage, systolic and diastolic blood pressure and lipid profile; probability of achieving good glycaemic control; probability of achieving remission from diabetes; probability of losing 5% and 10% body weight and modelled cardiovascular risk (UKPDS). An intention-to-treat within-trial cost-effectiveness analysis will be conducted from NHS and societal perspectives using participant-level data. Qualitative interviews will be conducted with participants to understand why and how the programme achieved its results and how participants manage their weight after the programme ends. ETHICS AND DISSEMINATION: Ethical approval was received from East of Scotland Research Ethics Service on 15 May 2018 (18/ES/0048). This protocol (V.3) was approved on 19 June 2019. Findings will be published in peer-reviewed scientific journals and communicated to other stakeholders as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN18399564.

Examining the factors that affect structural repetition in question answering.

We present two experiments that examine structural priming in the single-trial phone-call paradigm introduced by Levelt and Kelter (Cognitive psychology, 14 (1), 78-106, 1982). Experimenters called businesses and asked either What time do you close? or At what time do you close? Participants were more likely to produce a prepositional response (At 7 o'clock vs. 7 o'clock) following a prepositional question than following a non-prepositional question. Experiments 1 and 2 attempted to strengthen the priming effect by having the experimenters engage in a brief interaction with the participant before asking the What time…? question. The interactions did not reliably affect the observed priming effect. An analysis across experiments demonstrated that the priming effect found in this paradigm is generally smaller than the average structural priming effect (as reported in Mahowald, James, Futrell, & Gibson, Journal of Memory and Language, 91, 5-27, 2016), but within the range of the effects that are observed in different structural priming paradigms.

Adolescents' perspectives on a school-based physical activity intervention: A mixed method study.

Purpose: To examine adolescent experiences and perspectives of the GoActive intervention (ISRCTN31583496) using mixed methods process evaluation to determine satisfaction with intervention components and interpret adolescents' experiences of the intervention process in order to provide insights for future intervention design. Methods: Participants (n = 1542; 13.2 ±  0.4 years, mean ± SD) provided questionnaire data at baseline (shyness, activity level) and post-intervention (intervention acceptability, satisfaction with components). Between-group differences (boys vs. girls and shy/inactive vs. others) were tested with linear regression models, accounting for school clustering. Data from 16 individual interviews (shy/inactive) and 11 focus groups with 48 participants (mean = 4; range 2-7) were thematically coded. Qualitative and quantitative data were merged in an integrative mixed methods convergence matrix, which denoted convergence and dissonance across datasets. Results: Effect sizes for quantitative results were small and may not represent substantial between-group differences. Boys (vs. girls) preferred class-based sessions (ß = 0.2, 95% confidence interval (CI): 0.1-0.3); qualitative data suggested that this was because boys preferred competition, which was supported quantitatively (ß = 0.2, 95%CI: 0.1-0.3). Shy/inactive students did not enjoy the competition (ß = -0.3, 95%CI: -0.5 to -0.1). Boys enjoyed trying new activities more (ß = 0.1, 95%CI: 0.1-0.2); qualitative data indicated a desire to try new activities across all subgroups but identified barriers to choosing unfamiliar activities with self-imposed choice restriction leading to boredom. Qualitative data highlighted critique of mentorship; adolescents liked the idea, but older mentors did not meet expectations. Conclusion: We interpreted adolescent perspectives of intervention components and implementation to provide insights into future complex interventions aimed at increasing young people's physical activity in school-based settings. The intervention component mentorship was liked in principle, but implementation issues undesirably impacted satisfaction; competition was disliked by girls and shy/inactive students. The results highlight the importance of considering gender differences in preference of competition and extensive mentorship training.

Capturing the impact of adolescent inpatient admissions: The Social Connectedness Scale.

BACKGROUND: Outcome measurement is central to health service provision. In child and adolescent mental health services (CAMHS), there are established tools used to assess symptoms and track progress. However, there is a relative dearth of assessments of subjective well-being or recovery. Social connectedness is a concept linked with well-being and risk in young people. We sought to evaluate the utility and acceptability of a measure of social connectedness in inpatient CAMHS. METHOD: As part of routine clinical practice, we asked 92 young people (mean age 16 years old) on two inpatient CAMHS wards to complete the Social Connectedness Scale, alongside other assessments, and also comment on its acceptability. We repeated the measure on discharge from the unit. RESULTS: The findings showed that the measure was internally consistent (α = .910) and sensitive to change in this population. Scores also correlated with another self-report measure focusing on well-being and mental distress, but not with clinician-rated measures. Ratings of relevance and ease of understanding were reasonable and young people value social connection. CONCLUSION: The Social Connectedness Scale might offer an appropriate method of exploring this element of young peoples' experience and progress, as part of inpatient mental health admissions.

Results of a multicentre randomised controlled trial of cochlear-sparing intensity-modulated radiotherapy versus conventional radiotherapy in patients with parotid cancer (COSTAR; CRUK/08/004).

PURPOSE: About 40-60% of patients treated with post-operative radiotherapy for parotid cancer experience ipsilateral sensorineural hearing loss. Intensity-modulated radiotherapy (IMRT) can reduce radiation dose to the cochlea. COSTAR, a phase III trial, investigated the role of cochlear-sparing IMRT (CS-IMRT) in reducing hearing loss. METHODS: Patients (pT1-4 N0-3 M0) were randomly assigned (1:1) to 3-dimensional conformal radiotherapy (3DCRT) or CS-IMRT by minimisation, balancing for centre and radiation dose of 60Gy or 65Gy in 30 daily fractions. The primary end-point was proportion of patients with sensorineural hearing loss in the ipsilateral cochlea of ≥10 dB bone conduction at 4000 Hz 12 months after radiotherapy compared using Fisher's exact test. Secondary end-points included hearing loss at 6 and 24 months, balance assessment, acute and late toxicity, patient-reported quality of life, time to recurrence and survival. RESULTS: From Aug 2008 to Feb 2013, 110 patients (54 3DCRT; 56 CS-IMRT) were enrolled from 22 UK centres. Median doses to the ipsilateral cochlea were 3DCRT: 56.2Gy and CS-IMRT: 35.7Gy (p < 0.0001). 67/110 (61%) patients were evaluable for the primary end-point; main reasons for non-evaluability were non-attendance at follow-up or incomplete audiology assessment. At 12 months, 14/36 (39%) 3DCRT and 11/31 (36%) CS-IMRT patients had ≥10 dB loss (p = 0.81). No statistically significant differences were observed in hearing loss at 6 or 24 months or in other secondary end-points including patient-reported hearing outcomes. CONCLUSION: CS-IMRT reduced the radiation dose below the accepted tolerance of the cochlea, but this did not lead to a reduction in the proportion of patients with clinically relevant hearing loss.

Systems, supplies, and staff: a mixed-methods study of health care workers' experiences and health facility preparedness during a large national cholera outbreak, Kenya 2015.

BACKGROUND: From December 2014 to September 2016, a cholera outbreak in Kenya, the largest since 2010, caused 16,840 reported cases and 256 deaths. The outbreak affected 30 of Kenya's 47 counties and occurred shortly after the decentralization of many healthcare services to the county level. This mixed-methods study, conducted June-July 2015, assessed cholera preparedness in Homa Bay, Nairobi, and Mombasa counties and explored clinic- and community-based health care workers' (HCW) experiences during outbreak response. METHODS: Counties were selected based on cumulative cholera burden and geographic characteristics. We conducted 44 health facility cholera preparedness checklists (according to national guidelines) and 8 focus group discussions (FGDs). Frequencies from preparedness checklists were generated. To determine key themes from FGDs, inductive and deductive codes were applied; MAX software for qualitative data analysis (MAXQDA) was used to identify patterns. RESULTS: Some facilities lacked key materials for treating cholera patients, diagnosing cases, and maintaining infection control. Overall, 82% (36/44) of health facilities had oral rehydration salts, 65% (28/43) had IV fluids, 27% (12/44) had rectal swabs, 11% (5/44) had Cary-Blair transport media, and 86% (38/44) had gloves. A considerable number of facilities lacked disease reporting forms (34%, 14/41) and cholera treatment guidelines (37%, 16/43). In FDGs, HCWs described confusion regarding roles and reporting during the outbreak, which highlighted issues in coordination and management structures within the health system. Similar to checklist findings, FGD participants described supply challenges affecting laboratory preparedness and infection prevention and control. Perceived successes included community engagement, health education, strong collaboration between clinic and community HCWs, and HCWs' personal passion to help others. CONCLUSIONS: The confusion over roles, reporting, and management found in this evaluation highlights a need to adapt, implement, and communicate health strategies at the county level, in order to inform and train HCWs during health system transformations. International, national, and county stakeholders could strengthen preparedness and response for cholera and other public health emergencies in Kenya, and thereby strengthen global health security, through further investment in the existing Integrated Disease Surveillance and Response structure and national cholera prevention and control plan, and the adoption of county-specific cholera control plans.

Physical Activity Duration but Not Energy Expenditure Differs between Daily and Intermittent Breakfast Consumption in Adolescent Girls: A Randomized Crossover Trial.

Background: It is not known whether breakfast frequency affects physical activity (PA) in children or adolescents. Objective: This study examined the effect of daily compared with intermittent breakfast consumption on estimated PA energy expenditure (PAEE) in adolescent girls. Methods: Under a randomized crossover design, 27 girls [mean ± SD age: 12.4 ± 0.5 y, body mass index (in kg/m2): 19.3 ± 3.0] completed two 7-d conditions. A standardized breakfast (∼1674 kJ) was consumed every day before 0900 in the daily breakfast consumption (DBC) condition. The standardized breakfast was consumed on only 3 d before 0900 in the intermittent breakfast consumption (IBC) condition, alternating with breakfast omission on the remaining 4 d (i.e., only water consumed before 1030). Combined heart rate accelerometry was used to estimate PAEE throughout each condition. Statistical analyses were completed by using condition × time of day repeated-measures ANOVA. The primary outcome was PAEE and the secondary outcome was time spent in PA. Results: Daily estimated PAEE from sedentary or light-, moderate-, or vigorous-intensity PA and total PAEE were not significantly different between the conditions. The condition × time of day interaction for sedentary time (P = 0.05) indicated that the girls spent an additional 11.5 min/d being sedentary in the IBC condition compared with the DBC condition from 1530 to bedtime (P = 0.04). Light PA was 19.8 min/d longer in the DBC condition than in the IBC condition (P = 0.05), which was accumulated from waking to 1030 (P = 0.04) and from 1530 to bedtime (P = 0.03). There were no significant differences in time spent in moderate PA or vigorous PA between the conditions. Conclusions: Adolescent girls spent more time in light PA before 1030 and after school and spent less time sedentary after school when a standardized breakfast was consumed daily than when consumed intermittently across 7 d. However, breakfast manipulation did not affect estimated daily PAEE. This trial was registered at www.isrctn.com as ISRCTN74579070.

An evaluation of systematic errors on marker-based registration of computed tomography and magnetic resonance images of the liver.

We demonstrated a general method to evaluate systematic errors related to Magnetic Resonance (MR) imaging sequences in marker-based co-registration of MR and Computed Tomography (CT) images, and investigated the effect of MR image quality in the co-registration process using clinical MR and CT protocols for stereotactic ablative body radiotherapy (SABR) planning of the liver. Small systematic errors (under 1.6 mm) were detected, unlikely to be a clinical risk to liver SABR. The least favourable marker configuration was found to be a co-planar arrangement parallel to the transaxial image plane.

An external dosimetry audit programme to credential static and rotational IMRT delivery for clinical trials quality assurance.

PURPOSE: External dosimetry audits give confidence in the safe and accurate delivery of radiotherapy. The RTTQA group have performed an on-site audit programme for trial recruiting centres, who have recently implemented static or rotational IMRT, and those with major changes to planning or delivery systems. METHODS: Measurements of reference beam output were performed by the host centre, and by the auditor using independent equipment. Verification of clinical plans was performed using the ArcCheck helical diode array. RESULTS: A total of 54 measurement sessions were performed between May 2014 and June 2016 at 28 UK institutions, reflecting the different combinations of planning and delivery systems used at each institution. Average ratio of measured output between auditor and host was 1.002±0.006. Average point dose agreement for clinical plans was -0.3±1.8%. Average (and 95% lower confidence intervals) of gamma pass rates at 2%/2mm, 3%/2mm and 3%/3mm respectively were: 92% (80%), 96% (90%) and 98% (94%). Moderately significant differences were seen between fixed gantry angle and rotational IMRT, and between combination of planning systems and linac manufacturer, but not between anatomical treatment site or beam energy. CONCLUSION: An external audit programme has been implemented for universal and efficient credentialing of IMRT treatments in clinical trials. Good agreement was found between measured and expected doses, with few outliers, leading to a simple table of optimal and mandatory tolerances for approval of dosimetry audit results. Feedback was given to some centres leading to improved clinical practice.

Seeking Clearer Recommendations for Hand Hygiene in Communities Facing Ebola: A Randomized Trial Investigating the Impact of Six Handwashing Methods on Skin Irritation and Dermatitis.

To prevent disease transmission, 0.05% chlorine solution is commonly recommended for handwashing in Ebola Treatment Units. In the 2014 West Africa outbreak this recommendation was widely extended to community settings, although many organizations recommend soap and hand sanitizer over chlorine. To evaluate skin irritation caused by frequent handwashing that may increase transmission risk in Ebola-affected communities, we conducted a randomized trial with 91 subjects who washed their hands 10 times a day for 28 days. Subjects used soap and water, sanitizer, or one of four chlorine solutions used by Ebola responders (calcium hypochlorite (HTH), sodium dichloroisocyanurate (NaDCC), and generated or pH-stabilized sodium hypochlorite (NaOCl)). Outcomes were self-reported hand feel, irritation as measured by the Hand Eczema Score Index (HECSI) (range 0-360), signs of transmission risk (e.g., cracking), and dermatitis diagnosis. All groups experienced statistically significant increases in HECSI score. Subjects using sanitizer had the smallest increases, followed by higher pH chlorine solutions (HTH and stabilized NaOCl), and soap and water. The greatest increases were among neutral pH chlorine solutions (NaDCC and generated NaOCl). Signs of irritation related to higher transmission risk were observed most frequently in subjects using soap and least frequently by those using sanitizer or HTH. Despite these irritation increases, all methods represented minor changes in HECSI score. Average HECSI score was only 9.10 at endline (range 1-33) and 4% (4/91) of subjects were diagnosed with dermatitis, one each in four groups. Each handwashing method has benefits and drawbacks: soap is widely available and inexpensive, but requires water and does not inactivate the virus; sanitizer is easy-to use and effective but expensive and unacceptable to many communities, and chlorine is easy-to-use but difficult to produce properly and distribute. Overall, we recommend Ebola responders and communities use whichever handwashing method(s) are most acceptable, available, and sustainable for community handwashing. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Registry ISRCTN89815514.

Accuracy, Precision, Ease-Of-Use, and Cost of Methods to Test Ebola-Relevant Chlorine Solutions.

To prevent transmission in Ebola Virus Disease (EVD) outbreaks, it is recommended to disinfect living things (hands and people) with 0.05% chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% chlorine solution. In the current West African EVD outbreak, these solutions (manufactured from calcium hypochlorite (HTH), sodium dichloroisocyanurate (NaDCC), and sodium hypochlorite (NaOCl)) have been widely used in both Ebola Treatment Unit and community settings. To ensure solution quality, testing is necessary, however test method appropriateness for these Ebola-relevant concentrations has not previously been evaluated. We identified fourteen commercially-available methods to test Ebola-relevant chlorine solution concentrations, including two titration methods, four DPD dilution methods, and six test strips. We assessed these methods by: 1) determining accuracy and precision by measuring in quintuplicate five different 0.05% and 0.5% chlorine solutions manufactured from NaDCC, HTH, and NaOCl; 2) conducting volunteer testing to assess ease-of-use; and, 3) determining costs. Accuracy was greatest in titration methods (reference-12.4% error compared to reference method), then DPD dilution methods (2.4-19% error), then test strips (5.2-48% error); precision followed this same trend. Two methods had an accuracy of <10% error across all five chlorine solutions with good precision: Hach digital titration for 0.05% and 0.5% solutions (recommended for contexts with trained personnel and financial resources), and Serim test strips for 0.05% solutions (recommended for contexts where rapid, inexpensive, and low-training burden testing is needed). Measurement error from test methods not including pH adjustment varied significantly across the five chlorine solutions, which had pH values 5-11. Volunteers found test strip easiest and titration hardest; costs per 100 tests were $14-37 for test strips and $33-609 for titration. Given the ease-of-use and cost benefits of test strips, we recommend further development of test strips robust to pH variation and appropriate for Ebola-relevant chlorine solution concentrations.

Shelf-Life of Chlorine Solutions Recommended in Ebola Virus Disease Response.

In Ebola Virus Disease (EVD) outbreaks, it is widely recommended to wash living things (handwashing) with 0.05% (500 mg/L) chlorine solution and non-living things (surfaces, personal protective equipment, dead bodies) with 0.5% (5,000 mg/L) chlorine solution. Chlorine solutions used in EVD response are primarily made from powdered calcium hypochlorite (HTH), granular sodium dichloroisocyanurate (NaDCC), and liquid sodium hypochlorite (NaOCl), and have a pH range of 5-11. Chlorine solutions degrade following a reaction highly dependent on, and unusually sensitive to, pH, temperature, and concentration. We determined the shelf-life of 0.05% and 0.5% chlorine solutions used in EVD response, including HTH, NaDCC, stabilized NaOCl, generated NaOCl, and neutralized NaOCl solutions. Solutions were stored for 30 days at 25, 30, and 35°C, and tested daily for chlorine concentration and pH. Maximum shelf-life was defined as days until initial concentration fell to <90% of initial concentration in ideal laboratory conditions. At 25-35°C, neutralized-NaOCl solutions (pH = 7) had a maximum shelf-life of a few hours, NaDCC solutions (pH = 6) 2 days, generated NaOCl solutions (pH = 9) 6 days, and HTH and stabilized NaOCl solutions (pH 9-11) >30 days. Models were developed for solutions with maximum shelf-lives between 1-30 days. Extrapolating to 40°C, the maximum predicted shelf-life for 0.05% and 0.5% NaDCC solutions were 0.38 and 0.82 hours, respectively; predicted shelf-life for 0.05% and 0.5% generated NaOCl solutions were >30 and 5.4 days, respectively. Each chlorine solution type offers advantages and disadvantages to responders, as: NaDCC is an easy-to-import high-concentration effervescent powder; HTH is similar, but forms a precipitate that may clog pipes; and, NaOCl solutions can be made locally, but are difficult to transport. We recommend responders chose the most appropriate source chlorine compound for their use, and ensure solutions are stored at appropriate temperatures and used or replaced before expiring.