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Purpose Many people with dual diagnosis present with social complexity that impedes service access. The role of social work support in such service navigation is poorly understood. This study aims to characterise client presentations to an Australian telephone-based social work alcohol and other drug (AOD) service navigation and linkage program, with consideration of presentation complexity compared between those clients who present with or without self-reported mental health (MH) concerns and a history of MH diagnoses, to identify differences in baseline characteristics, and linkage outcomes. Design/methodology/approach A retrospective audit was conducted of routinely collected clinical information from a six-month period, selected to capture the social and health challenges experienced during the mid-pandemic period (mid-2021) in Victoria, Australia, during which a number of lockdowns resulted in a reliance on telephone-based services. The audit focused on client and presentation characteristics, and compared clients with and without a history of co-occurring MH and AOD concerns. Findings It was found that three in four people accessing an Australian telephone-based AOD service navigation and linkage program presented with dual diagnosis. Individuals with dual diagnosis required more support from the service compared to those without a co-occurring MH disorder; but overall, were just as likely to achieve a successful linkage to services, when offered holistic, long-term social work support. Originality/value This study focused on the role of social workers in this service navigation program in supporting individuals with complexity. It also highlights the challenges in operationalising social complexity factors alongside clinical MH and AOD diagnoses, and points to the need for further research to guide future service development for this vulnerable client group.

PURPOSE: The aim of this study was to apply the Six Sigma methodology and failure mode and effect analysis (FMEA) to mitigate errors in intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) treatment planning with the first clinical installation of RefleXion X1. METHODS AND MATERIALS: The Six Sigma approach consisted of 5 phases: define, measure, analyze, improve, and control. The define, measure, and analyze phases consisted of process mapping and an FMEA of IMRT and SBRT treatment planning on the X1. The multidisciplinary team outlined the workflow process and identified and ranked the failure modes associated with the plan check items using the American Association of Physicists in Medicine Task Group 100 recommendations. Items with the highest average risk priority numbers (RPNs) and severity ≥7 were prioritized for automation using the Eclipse Scripting Application Programming Interface (ESAPI). The “improve” phase consisted of developing ESAPI scripts before the clinical launch of X1 to improve efficiency and safety. In the “control” phase, the FMEA ranking was re-evaluated 1 year after clinical launch. RESULTS: Overall, 100 plan check items were identified in which the RPN values ranged from 10.2 to 429.0. Fifty of these items (50%) were suitable for automation within ESAPI. Of the 10 highest-risk items, 8 were suitable for automation. Based on the results of the FMEA, 2 scripts were developed: Planning Assistant, used by the planner during preparation for planning, and Automated Plan Check, used by the planner and the plan checker during plan preparation for treatment. After 12 months of clinical use of the X1 and developed scripts, only 3 errors were reported. The average prescript RPN was 138.0, compared with the average postscript RPN of 47.8 (P < .05), signifying a safer process. CONCLUSIONS: Implementing new technology in the clinic can be an error-prone process in which the likelihood of errors increases with increasing pressure to implement the technology quickly. To limit errors in clinical implementation of the novel RefleXion X1 system, the Six Sigma method was used to identify failure modes, establish quality control checks, and re-evaluate these checks 1 year after clinical implementation.

Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical samples with cross-sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life-story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.

The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson’s disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson’s disease sleep scale (PDSS-2), and Beck depression inventory (BDI). Our results showed significantly decreased PACAP levels in PD patients without deep brain stimulation (DBS) therapy and in akinetic-rigid subtype; additionally we also observed a further decrease in the HY stage 3 and 4. Elevated PACAP levels were found in patients with DBS. There were no significant correlations between PACAP level with MDS-UPDRS, type of pharmacological treatment, PDSS-2 sleepiness, or depression (BDI) scales, but we found increased PACAP level in patients with more severe sleepiness problems based on the ESS scale. Based on these results, we suggest that following the alterations of PACAP with other frequently used clinical biomarkers in PD patients might improve strategic planning of further therapeutic interventions and help to provide a clearer prognosis regarding the future perspective of the disease.

In polytrauma patients who survive the primary insult, the imbalance between the pro- and anti-inflammatory processes seems to be responsible for life-threatening complications such as sepsis or multiple organ dysfunction syndrome. Measurement of C-reactive protein (CRP) and procalcitonin (PCT) is a standard way for differentiating between infectious (bacterial) and non-infectious inflammation. Monitoring of immune cell functions, like leukocyte anti-sedimentation rate (LAR) can also be useful to diagnose infectious complications. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with well-known immunomodulatory and anti-inflammatory effects. The aim of our study was to determine the changes of PACAP38 levels in polytrauma patients in the early post-traumatic period in intensive care unit and analyse possible correlation of its level with conventional (CRP, PCT) and unconventional (LAR) laboratory parameters. Twenty polytrauma patients were enrolled. Blood samples were taken daily for five days. We observed significant correlation between PACAP38 and CRP levels on day 4 and 5 as well as between PACAP38 and LAR levels all of the days. This could be due to the anti-inflammatory and cytoprotective functions of PACAP38 as part of an endogenous response to the trauma induced systemic inflammatory response syndrome. These significant correlations could have clinical importance in monitoring the dynamic balance of pro- and anti-inflammatory processes in case of polytraumatic patients.

Objective To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. Materials and Methods This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan–Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. Results Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1–2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4–5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). Conclusion The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.

Background Suicide prevention remains challenging among youth, as many do not disclose suicidal ideation. Nearly one-third of American Indian and Alaska Native (AI and AN, tribal, or native) youth see concerning messages on social media at least weekly. Objective To prepare adults to support AI and AN youth who post or view concerning messages, our team designed an hour-long training: Responding to Concerning Posts on Social Media. This study tested the usability, appeal, and impact of the training. Methods A purposive sample of 70 adults was recruited to participate in the pilot, which included 2 study arms. Arm 1 participants completed a 30-min training video and reviewed accompanying handouts, including the Viewer Care Plan (VCP). The VCP provided a 3-step planning and response tool: (1) Start the Conversation, (2) Listen, Gather Information, and Assess Viewer Experience, and (3) Plan and Act. The intent of the VCP was to support and connect AI and AN youth who either view or post concerning messages on social media to life-saving resources. Those enrolled in arm 2 participated in an additional interactive role-play scenario with a coach that took place after the training, via text message. Participants provided qualitative and quantitative feedback on the training’s relevance, appeal, and utility. Paired t tests were used to assess confidence in addressing concerning posts between pre- and postsurveys. Content analysis of the role-play transcripts was used to assess the quality and completion of the coached role-plays, in relation to the recommended VCP. Results Altogether, 35 participants finished the training and completed pre- and postsurveys; 22 participants completed the 6-month follow-up survey. Pre-post analyses of differences in means found significant improvement across several efficacy measures, including confidence starting a conversation about social media (P=.003), confidence contacting the person who posted something concerning (P Conclusions Findings indicate that the Responding to Concerning Posts on Social Media training is a promising tool to prepare adults to intervene and complete the VCP. Additional evaluation with a larger cohort of participants is needed to determine the unique impact of the role-play scenario and changes in mental health referral rates, behaviors, and skills.

In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites.A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale.In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (4 weeks) after completing the modules (P 0.001). For most there was significant increase in confidence (P 0.001) after completing all the modules.

Aim To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases. Materials and methods A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26Gy was prescribed for peripheral targets and 18Gy for central targets. In the multi-fraction cohort, 48Gy/4 or 50Gy/5 was prescribed for peripheral targets and 50Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion. Results Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% ( P = 0.01), but a higher median R100% than IMRT/VMAT ( P = 0.04). The R50% index was inversely correlated to the PTV with all techniques ( P = 0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87–100%) and 71% (95% confidence interval 58–86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86–100%) and 38% (95% confidence interval 27–55%), respectively. There were no significant differences between overall survival ( P = 0 .14), time to distant progression ( P = 0.06) or toxicity rates ( P = 0.75) between single- and multi-fraction cohorts. Conclusion We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms.

To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation/perfusion (V/Q) PET/CT.In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters.The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively.IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality.

Collected real-life clinical target volume (CTV) displacement data show that some patients undergoing external beam radiotherapy (EBRT) demonstrate significantly more fraction-to-fraction variability in their displacement ('random error') than others. This contrasts with the common assumption made by historical recipes for margin estimation for EBRT, that the random error is constant across patients. In this work we present statistical models of CTV displacements in which random errors are characterised by an inverse gamma (IG) distribution in order to assess the impact of random error variability on CTV-to-PTV margin widths, for eight real world patient cohorts from four institutions, and for different sites of malignancy. We considered a variety of clinical treatment requirements and penumbral widths. The eight cohorts consisted of a total of 874 patients and 27 391 treatment sessions. Compared to a traditional margin recipe that assumes constant random errors across patients, for a typical 4 mm penumbral width, the IG based margin model mandates that in order to satisfy the common clinical requirement that 90% of patients receive at least 95% of prescribed RT dose to the entire CTV, margins be increased by a median of 10% (range over the eight cohorts -19% to +35%). This substantially reduces the proportion of patients for whom margins are too small to satisfy clinical requirements.

To describe our 3-dimensional conformal planning approaches and report early toxicities with stereotactic body radiation therapy for the management of primary renal cell carcinoma.This is an analysis of a phase 1 trial of stereotactic body radiation therapy for primary inoperable renal cell carcinoma. A dose of 42 Gy/3 fractions was prescribed to targets ≥5 cm, whereas for5 cm 26 Gy/1 fraction was used. All patients underwent a planning 4-dimensional CT to generate a planning target volume (PTV) from a 5-mm isotropic expansion of the internal target volume. Planning required a minimum of 8 fields prescribing to the minimum isodose surrounding the PTV. Intermediate dose spillage at 50% of the prescription dose (R50%) was measured to describe the dose gradient. Early toxicity (6 months) was scored using the Common Terminology Criteria for Adverse Events (v4.0).From July 2012 to August 2013 a total of 20 patients (median age, 77 years) were recruited into a prospective clinical trial. Eleven patients underwent fractionated treatment and 9 patients a single fraction. For PTV targets100 cm(3) the median number of beams used was 8 (2 noncoplanar) to achieve an average R50% of 3.7. For PTV targets100 cm(3) the median beam number used was 10 (4 noncoplanar) for an average R50% value of 4.3. The R50% was inversely proportional to decreasing PTV volume (r=-0.62, P=.003) and increasing total beams used (r=-0.51, P=.022). Twelve of 20 patients (60%) suffered grade ≤2 early toxicity, whereas 8 of 20 patients (40%) were asymptomatic. Nausea, chest wall pain, and fatigue were the most common toxicities reported.A 3-dimensional conformal planning technique of 8-10 beams can be used to deliver highly tolerable stereotactic ablation to primary kidney targets with minimal early toxicities. Ongoing follow-up is currently in place to assess long-term toxicities and cancer control.

Aims To measure the difference in cumulative doses received by the bladder (target) and integral doses with different clinical target volume (CTV) to planning target volume (PTV) margins, comparing set-up to skin tattoos versus image-guided radiotherapy to bone or soft tissue. Materials and methods Four plans were generated on each planning computed tomography dataset using the CTV with 5, 10, 15, 20 mm PTV margins using a three-dimensional conformal four-field technique. Set-up data based on skin, bone and soft tissue to the bladder on pre-treatment cone beam computed tomography (CBCT) were recorded. In total, 316 CBCTs were evaluable from 10 bladder cancer patients. Each CBCT was fused to the planning computed tomography dataset using the isocentre corresponding to each of the three pre-treatment matching conditions. The target was contoured on each CBCT and called the CTV of the day and the plan was re-calculated to determine the dose to this. Results The mean D95 with CTV to PTV margins of 5, 10, 15 and 20 mm for skin set-up was 89.4, 93.0, 97.2, 98.6; for bone 88.8, 92.6, 96.7, 98.6; and for soft tissue 96.3, 98.6, 98.7, 99.5. With soft-tissue matching, the mean (standard deviation) volume of normal tissue receiving 5 Gy with 5, 10, 15 and 20 mm margins was 3899 (1022), 4561 (1142), 5663 (1304) and 6315 (1426) in cm 3 . Conclusion Soft-tissue matching results in superior target coverage and a reduced integral dose to the surrounding tissues. With soft-tissue matching, increasing CTV to PTV margins progressively beyond 5 mm results in modest improvement in CTV coverage, but a large increase in integral dose.

Objectives Clinically significant minor depression is among the most common mental disorders in the elderly individuals and is associated with considerable medical and psychosocial morbidity. Despite its clinical impact, the biological basis of minor depression in the elderly individuals remains poorly understood. The purpose of our current study was to examine cortical thickness in a sample of patients with late-life minor depression and non-depressed comparison subjects using magnetic resonance imaging (MRI). Design Cross-sectional analysis. Setting Community. Participants Patients (n = 16; mean age = 76.2 ± 7.5) met modified DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for minor depression and were free of other brain diseases. Healthy comparison subjects (HC; n = 16) were of comparable age and gender distribution. Measurements All subjects were scanned on a 1.5-Tesla GE scanner and brain regions were outlined using Freesurfer Image Analysis. Results Results show that patients with minor depression have cortical thinning in the right cingulate cortex compared to HC. Conclusions These findings indicate that abnormalities in specific structures and associated neural circuitry may underlie minor and major depression in the elderly individuals and the pathophysiological abnormalities are comparable in major and less severe forms of the disorder.

The European rabbit (Oryctolagus cuniculus) belongs to the most invasive and successful mammalian species, which is distributed nearly worldwide. In Europe, they inhabit broad parts of the mainland and subsequently reached several European islands via anthropogenic diversion. Rabbits can also serve as hosts for numerous parasite species. The parasite and pathogen fauna of O. cuniculus have been well documented in various European countries, although studies in Germany are scarce. Until now, a comprehensive survey combining recent international studies over parasite fauna of wild rabbits had not been conducted. We examined 50 wild rabbits from an urban area near Aachen (Germany) to identify their metazoan parasite fauna, and then compared our findings to previous international investigations. A total of nine parasite species were isolated consisting of four endoparasite species (Cittotaenia denticulata, Graphidium strigosum, Passalurus ambiguus, and Trichostrongylus retortaeformis) and five ectoparasite species (Cheyletiella parasitivorax, Ixodes ricinus, Leporacarus gibbus, Haemodipsus ventricosus, and Spilopsyllus cuniculi). Among the ectoparasites were two verifiable human pathogenic species and two potentially pathogenic species. In comparison to previous studies, a high number of similarities in composition of helminth species fauna were revealed. Furthermore, our results showed partial agreement with international surveys in prevalence and mean intensity of the parasites C. denticulata, G. strigosum, P. ambiguus, and T. retortaeformis.

An e-Learning programme appeared useful for providing training and information regarding a multi-centre image guided radiotherapy trial. The aim of this study is to demonstrate the utility of this e-Learning programme.Modules were created on relevant pelvic anatomy, Cone Beam CT soft tissue recognition and trial details. Radiation therapist participants' knowledge and confidence were evaluated before, at the end of, and after at least 6 weeks of e-Learning (long term).One hundred and eighty-five participants were recruited from 12 centres, with 118 in the first, and 67 in the second cohort. One hundred and forty-six participants had two tests (pre and post e-Learning) and 39 of these had three tests (pre, post, and long term). There was an increase confidence after completion of modules (p0.001). The first cohort pre scores increased from 67 ± 11 to 79 ± 8 (p0.001) post. The long term same question score was 73 ± 14 (p=0.025, comparing to pre-test), and different questions' score was 77 ± 13 (p=0.014). In the second cohort, pre-test scores were 64 ± 10, post-test same question score 78 ± 9 (p0.001) and different questions' score 81 ± 11 (p0.001).e-Learning for a multi-centre clinical trial was feasible and improved confidence and knowledge.

Introduction: The purpose of this study is to assess the impact of a vacuum immobilisation system on reproducibility of patient set-up, interfraction stability and tumour motion amplitude. Methods: From February 2010 to February 2012 as part of a prospective clinical trial 12 patients with solitary pulmonary metastases had consecutive four-dimensional computed tomography (4DCT) scans performed with and without vacuum immobilisation. The displacement of the tumour centroid position was recorded in each of the 10 phases of the 4DCT reconstruction. A further six patients with seven metastases underwent single fraction stereotactic ablative body radiotherapy (SABR) during this period (a total of 19 targets) and were included in an analysis of positional reproducibility and intrafraction immobilisation. Couch shifts recorded in the medio-lateral (X), cranio-caudal (Y) and ventero-dorsal (Z) planes. Results: For the 19 treatments delivered, the median (0–90% range) shift required immediately pretreatment was 1 mm (0–3) in the X-plane, 2 mm (0–6) in the Y-plane and 4 mm (0–8) in the Z-plane, respectively. The mean (+/− standard deviation) of mid-treatment shifts were 0.3 mm (+/− 0.7), 1.1 mm (+/− 2) and 0.8 mm (+/− 1.5) in the X, Y and Z planes, respectively. Mid-treatment shifts were

Purpose To compare the cone-beam CT (CBCT) soft tissue localization disparity between radiation oncologists (RO) and radiation therapy technologists (RTT) in a novel online protocol of image-guided adaptive radiotherapy to the postoperative prostate bed. Method Using the planning CT and pre-treatment CBCTs from the first week of radiotherapy, four adaptive plans of different sizes were derived for each of eight post-prostatectomy patients. Four ROs collectively defined the reference answer, i.e. the plan of the day and isocentre correction for 40 CBCTs taken in weeks 2–6 of treatment for each patient. RTTs were randomly assigned five of these CBCTs; and asked to record their plan of the day selection and isocentre correction. RTT selection and reference answers were compared. The distance between the RTT selection and the reference answer was calculated. Results A total of 33 RTTs took part in this study. The average difference in CTV volume (reference answer-RTT selection) was 1.32cm 3 (SD 29cm 3 ) overall. The average difference between reference answer and RTT isocentre coordinates was SI 1mm (SD 4.8mm), LR 1.1mm (SD 4.0mm) and AP −0.2mm (SD 3.9mm). Distance of superior 8mm, inferior 6mm, left 4mm, right 2mm, anterior 6mm and posterior 6mm covered 100% of the CTV in 90% of fractions. Conclusion The difference between RTT and RO selection of adaptive volumes is small and can be accounted for in a clinically acceptable CTV to PTV margin. Adaptive post-prostatectomy radiotherapy is feasible, in the setting of an academic center although at the moment, we have insufficient evidence to suggest that margins can yet be reduced with IGART with the current protocol.

Purpose The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. Methods and Materials Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatment and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patient's bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. Results The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. Conclusion Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.

Online adaptive radiotherapy for bladder cancer is a novel radiotherapy technique that was found feasible in a pilot study at a single academic institution. In September 2010 this technique was opened as a multicenter study through the Trans-Tasman Radiation Oncology Group (TROG 10.01 bladder online adaptive radiotherapy treatment). Twelve centers across Australia and New-Zealand registered interest into the trial. A multidisciplinary team of radiation oncologists, radiation therapists and medical physicists represented the trial credentialing and technical support team. To provide timely activation and proper implementation of the adaptive technique the following key areas were addressed at each site: Staff education/training; Practical image guided radiotherapy assessment; provision of help desk and feedback. The trial credentialing process involved face-to-face training and technical problem solving via full day site visits. A dedicated "help-desk" team was developed to provide support for the clinical trial. 26% of the workload occurred at the credentialing period while the remaining 74% came post-center activation. The workload was made up of the following key areas; protocol clarification (36%), technical problems (46%) while staff training was less than 10%. Clinical trial credentialing is important to minimizing trial deviations. It should not only focus on site activation quality assurance but also provide ongoing education and technical support.

Purpose To assess out-of-field dose using three different variants of LiF thermoluminescence dosimeters (TLD) for ten patients who underwent stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) and compare with treatment planning system (TPS) dose calculations. Methods and materials Thermoluminescent dosimeter (TLD) measurements were conducted at 20, 30, 40 and 50 cm from isocentre on ten patients undergoing SABR for primary RCC. Three types of high-sensitivity LiF:Mg,Cu,P TLD material with different 6Li/7Li isotope ratios were used. Patient plans were calculated using Eclipse Anisotropic Analytical Algorithm (AAA) for clinical evaluation and recalculated using Pencil Beam Convolution (PBC) algorithm for comparison. Results Both AAA and PBC showed diminished accuracy for photon doses at increasing distance out-of-field. At 50 cm, measured photon dose was 0.3 cGy normalised to a 10 Gy prescription on average with only small variation across all patients. This is likely due to the leakage component of the out-of-field dose. The 6Li-enriched TLD materials showed increased signal attributable to additional neutron contribution. Conclusion LiF:Mg,Cu,P TLD containing 6Li is sensitive enough to measure out-of-field dose 50 cm from isocentre however will over-estimate the photon component of out-of-field dose in high energy treatments due to the presence of thermal neutrons. 7Li enriched materials which are insensitive to neutrons are therefore required for accurate photon dosimetry. Neutron signal has been shown here to increase with MUs and is higher for patients treated using certain non coplanar beam arrangements. Further work is required to convert this additional neutron signal to dose.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases.METHODS/DESIGN: The TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study.DISCUSSION: Fractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR.TRIALS REGISTRATION: ACTRN12613001157763 , registered 17th October 2013.

Aims To determine the clinical target volume (CTV) to planning target volume (PTV) margins required for bladder coverage when using skin or bony or soft tissue matching on a daily basis. Materials and methods Twenty-seven patients with T2–T4 transitional cell carcinoma of the bladder were treated with daily online adaptive image-guided radiotherapy using cone beam computed tomography. All daily CTVs were contoured by a single observer. A retrospective comparison of coverage of the bladder CTV using skin, bone and soft tissue matching was conducted. Results With the skin set-up, bladder CTV coverage with a margin of 0.5, 1.0, 1.5, 2.0 and 2.5 cm was 0, 19, 56, 93 and 96%, respectively. For the daily set-up based on bone, the respective coverage was 0, 41, 63, 89 and 96%. For soft tissue set-up based on the geometric centre of the bladder, coverage was 52, 89, 96, 100 and 100%, respectively. Conclusions Based on coverage of the CTV, the required CTV to PTV margins are smaller for the daily online soft tissue set-up compared with skin or bone.

Study Type – Therapy (systematic review) Level of Evidence 1a What's known on the subject? and What does the study add? At present, little is known about the role of stereotactic ablative body radiotherapy in the treatment of primary renal cell carcinoma. The published evidence to date totals 126 patients worldwide. The majority of evidence is retrospective in nature. The present study adds context to the current literature by providing an overall summary of the evidence. OBJECTIVE • To critically assess the use of stereotactic ablative body radiotherapy (SABR) for the treatment of primary renal cell carcinoma with particular focus on local control and toxicity outcomes. METHODS • A systematic search on PubMed was performed in January 2012 independently by two radiation oncologists using structured search terms. • Secondary manual searches were performed on citations in relevant publications and abstracts in major radiotherapy journals. • Outcomes, techniques, biological doses and scientific rigour of the studies were analysed. RESULTS • In total 10 publications (seven retrospective and three prospective) were identified. A wide range of techniques, doses and dose fractionation schedules were found. • A total of 126 patients were treated with between one and six fractions of SABR. Median or mean follow-up ranged from 9 to 57.5 months. A weighted local control was reported of 93.91% (range 84%–100%). • The weighted rate of severe grade 3 or higher adverse events was 3.8% (range 0%–19%). The weighted rate of grade 1–2 minor adverse events was 21.4% (range 0%–93%). The most commonly employed fractionation schedule was 40 Gy delivered over five fractions. CONCLUSIONS • Current literature suggests that SABR for primary renal cell carcinoma can be delivered with promising rates of local control and acceptable toxicity. • However, there was insufficient evidence to recommend a consensus view for dose fractionation or technique. • This indicates the need for further prospective studies assessing the role of this technique in medically inoperable patients.

Introduction Plan-of-the-day adaptive radiotherapy (ART) that has not been optimally designed may result in inefficient plan sizes. This can lead to unused plans, which may potentially reduce overall conformality. We compared two methods of individualising ART plan sizes for muscle-invasive bladder cancer to determine which provides a more balanced distribution of plan selections. Methods Twenty-seven previously treated patients had small, medium and large ART plans generated from CTV contours on the simulation CT and initial cone beam CTs (CBCT). In the original clinical method, the smallest plan was based on the smallest CTV, while the experimental method used the Boolean summation of the two smallest CTVs. The large plan was identical in both methods. The medium plans were created midway between small and large CTVs. Credentialed treatment staff performed plan selection clinically for the original plans and retrospectively for the experimental plans. Results A total of 646 CBCTs from 26 patients were included. The small, medium and large adaptive CTVs, and the conventional CTV, were used 29.7%, 45.4%, 22.0% and 2.9% of the time, respectively, compared to the previous 9.8%, 49.2%, 39.5% and 1.5%. The differences were significant between previous and new CTV (small), and CTV (large). Conclusions The new design method resulted in the three adaptive CTV choices being selected more evenly, however, a reduction in a surrogate for normal tissue irradiation was not observed.

Background: Daily variations in bladder filling make conformal treatment of bladder cancer challenging. On-line adaptive radiotherapy with a choice of plans has been demonstrated to reduce small bowel irradiation in single institution trials. In order to support a multicentre feasibility clinical trial on adaptive radiotherapy for bladder cancer (TROG 10.01) a credentialing programme was developed for centres wishing to participate. Methods: The credentialing programme entails three components: a facility questionnaire; a planning exercise which tests the ability of centres to create three adaptive plans based on a planning and five cone beam CTs; and a site visit during which image quality, imaging dose and image guidance procedures are assessed. Image quality and decision making were tested using customised inserts for a Perspex phantom (Modus QUASAR) that mimic different bladder sizes. Dose was assessed in the same phantom using thermoluminescence dosimetry (TLD). Results: All 12 centres participating in the full credentialing programme were able to generate appropriate target volumes in the planning exercise and identify the correct target volume and position the bladder phantom in the phantom within 3 mm accuracy. None of the imaging doses exceeded the limit of 5 cGy with a CT on rails system having the lowest overall dose. Conclusion: A phantom mimicking the decision making process for adaptive radiotherapy was found to be well suited during site visits for credentialing of centres participating in a clinical trial of adaptive radiotherapy for bladder cancer. Combined with a planning exercise the site visit allowed testing the ability of centres to create adaptive treatment plans and make appropriate decisions based on the volumetric images acquired at treatment.

Purpose: The purpose of this study was to compare and evaluate radiotherapy treatment plans using volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) for post-prostatectomy radiotherapy. Methods and Materials: The quality of radiotherapy plans for 10 patients planned and treated with a seven-field IMRT technique for biochemical failure post-prostatectomy were subsequently compared with 10 prospectively planned single-arc VMAT plans using the same computed tomography data set and treatment planning software. Plans were analysed using parameters to assess for target volume coverage, dose to organs at risk (OAR), biological outcomes, dose conformity and homogeneity, as well as the total monitor units (MU), planning and treatment efficiency. Results: The mean results for the study population are reported for the purpose of comparison. For IMRT, the median dose to the planning target volume, V95% and D95% was 71.1 Gy, 98.9% and 68.3 Gy compared with 71.2 Gy, 99.2% and 68.6 Gy for VMAT. There was no significant difference in the conformity index or homogeneity index. The VMAT plans achieved better sparing of the rectum and the left and right femora with a reduction in the median dose by 7.9, 6.3 and 3.6 Gy, respectively. The total number of monitor units (MU) was reduced by 24% and treatment delivery time by an estimated 3 min per fraction without a significant increase in planning requirements. Conclusions: VMAT can achieve post-prostatectomy radiotherapy plans of comparable quality to IMRT with the potential to reduce dose to OAR and improve the efficiency of treatment delivery.

This paper presents the development and characterization of self-aligned carbon nanotube thin-film transistors (CNT-TFT) on flexible substrates. The channel consisting of dense, aligned, 99% pure semiconducting single-walled CNT is deposited using the dip-coat technique on a sacrificial substrate and then transferred on the device substrate. The source, drain, and gate structures are formed by the ink-jet printing technique. A novel source-drain contact formation using wet droplet of silver ink prior to the CNT thin-film application has been developed to enhance source-drain contact with the CNT channel. Bending test data on CNT-TFT test structures show minimal change (less than 10%) in their performance. Moreover, a special multilayer metal interconnection technology is demonstrated for flexible electronics applications. Bending test data on via test structure show change in resistance by less than 5%.

We present a conformal ink-jet printed 2-bit four-element phased-array antenna (PAA) without any lithography process. Passive and active components, such as microstrip transmission lines, phase shifters, and RF power distribution networks are all developed adopting a room-temperature printing process. The PAA working at 5.2 GHz is printed on flexible DuPont Kapton flexible printed circuit polyimide film to demonstrate the conformal nature. High-speed carbon-nanotube-based field-effect transistors (FETs) function as switches to route the RF signal go through different segments of the true-time delay lines. The FET switch exhibits an on-off ratio of over 1000 and current of 3.6 mA is obtained at a low source-drain bias of 0.8 V. The 2-bit azimuth beamsteering angles of the PAA are measured and confirmed to agree well with simulation values.

The purpose of this study was to examine the effect of type 2 diabetes with major depression on cortical gray matter using magnetic resonance imaging and cortical pattern matching techniques. We hypothesized that diabetic subjects and depressed diabetic subjects would demonstrate decreased cortical gray matter thickness in prefrontal areas as compared to healthy control subjects. Patients with type 2 diabetes (n=26) and patients with diabetes and major depression (n=26) were compared with healthy controls (n=20). Gray matter thickness across the entire cortex was measured using cortical pattern matching methods. All subjects with diabetes demonstrated decreased cortical gray matter thickness in the left anterior cingulate region. Additionally, depressed diabetic subjects showed significant cortical gray matter decreases in bilateral prefrontal areas compared with healthy controls. Correlations between clinical variables and cortical gray matter thickness revealed a significant negative relationship with cerebrovascular risk factors across all three groups, most consistently in the left dorsomedial prefrontal cortex. A significant positive relationship between performance on attention and executive function tasks and cortical gray matter thickness predominantly in left hemisphere regions was also seen across all subjects. Depression and diabetes are associated with significant cortical gray matter thinning in medial prefrontal areas.

Objective Self-perceived emotional vitality, intact mood, physical activity, and social engagement are recognized as important indicators for lowered rates of morbidity and increased longevity in late-life, but little is known about their underlying neural substrates. This study examined relationships between self-reported levels of general functioning and the combined volume of three integrated prefrontal structures associated with self-perception and emotion. Design Cross-sectional. Setting UCLA Semel Institute for Neuroscience, Los Angeles. Participants Depressed (N = 43) and comparison (N = 41) elderly subjects. Measurements Magnetic resonance images of orbitofrontal, gyrus rectus, and anterior cingulate gray and white matter volumes were corrected for intracranial volume and combined across structures to form white matter and gray matter scales. Subjects completed the RAND Short-Form 36 Questionnaire, a self-report evaluation of daily functioning. Subscales used for analysis were physical function, energy, and general health, which were not correlated with depression. Results White matter volumes were associated with self-perceptions of Energy for healthy as well as depressed individuals, and gray matter volume was associated with General Health. This latter association was strongest among patients with late-onset of depression, i.e., onset > age 50, although it appeared in all diagnostic groups. Conclusions Although mild to moderate atrophy is expected in late-life, prefrontal atrophy may represent changes to neuroanatomic substrates that qualitatively modulate self-perceptions of energy and general health for both depressed and nondepressed persons.

Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early- and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated.With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early- (N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups.Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early- and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late- compared to early-onset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1-CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late- but not early-onset depressed patients or comparison subjects.More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies.

To evaluate renal dysfunction after stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma (RCC) using nuclear medicine assessments.In a prospective clinical trial, patients received single fraction renal SABR (26 Gy) for tumours5 cm, or fractionated SABR (3 × 14 Gy) for tumours ⩾5 cm. Global and regional glomerular filtration rate (GFR) was calculated through (51)Cr-EDTA and (99m)Tc-DMSA SPECT/CT, respectively, at baseline and post-treatment (14, 90 days and at 1-year). Regional loss in function was correlated to the absolute and biologically effective doses (BED) delivered.In 21 patients the mean (range) tumour size was 48 mm (21-75 mm). The mean ± SD GFR at baseline was 52 ± 24 ml/min. Net change in mean GFR was +0.6 ± 11.3, +3.2 ± 14.5 and -8.7 ± 13.4 ml/min (p=0.03) at 2 weeks, 3 months and 1 year, respectively. For every 10 Gy of physical dose delivered, an exponential decline in affected kidney GFR was observed at 39% for 26 Gy/1 fraction and 25% for 42 Gy/3 fractions. When normalised to BED3Gy, the dose-response relationship for each treatment prescription was similar with a plateau beyond 100 Gy. The R50% conformity index correlated with GFR loss (p=0.04). No patient required dialysis.SABR results in clinically acceptable and dose-dependent renal dysfunction at 1-year. Sparing functional kidney from high-dose regions (50% isodoses) may help reduce risk of functional loss.

Stereotactic ablative body radiation therapy for primary kidney cancer treatment relies on motion management that can quantify both the trajectory of kidney motion and stabilize the patient. A prospective ethics-approved clinical trial of stereotactic treatment to primary kidney targets was conducted at our institution. Our aim was to report on specific kidney tumor motion and the inter- and intrafraction motion as seen on treatment.Patients with tumor size5 cm received a dose of 26 Gy in 1 fraction and those with tumor size ≥5 cm received 42 Gy in 3 fractions. All patients underwent a 4-dimensional computed tomography planning scan, immobilized in a dual-vacuum system. A conventional linear accelerator cone beam computed tomography scan was used for pre-, mid-, and posttreatment imaging to verify target position.Between July 2012 and October 2014, 33 targets from 32 consecutive patients (24 males/8 females) were treated. Seventeen targets were prescribed 26 Gy/1 fraction and the remaining 16 targets received 42 Gy/3 fractions. Kidney motion at each of the poles was not affected by the presence of tumor (P = .875), nor was the motion statistically different from the corresponding contralateral kidney pole (P = .909). The mean 3-dimensional displacement of the target at mid- and posttreatment was 1.3 mm (standard deviation ± 1.6) and 1.0 mm (standard deviation ± 1.3), respectively. The maximum displacement in any direction for 95% of the fractions at mid- and posttreatment was ≤3 mm.In summary, stereotactic ablative body radiation therapy of primary kidney targets can be accurately delivered on a conventional linear accelerator with protocol that has minimal intrafractional target motion.

To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI).Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex.Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities.The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.

Background Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. Findings In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and 51Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. Conclusions The pattern of renal functional change in 99mTc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.