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Background: Erectile dysfunction (ED) is common after prostate cancer treatment. It has been studied for conventional radiotherapy, but associations in the hypofractionated radiotherapy context are less clear. This study aimed to determine which factors are predicted for worsening ED after highly conformal, modestly hypofractionated radiotherapy to the prostate. Methods: Two hundred and twelve patients treated with 6000 cGy in twenty fractions across four centers were included in this study. Demographic, clinical, and dosimetry factors were then evaluated for post-treatment declines in erectile function using logistic regression and an explainable machine learning-based neural network. Results: 212 patients with a median follow-up of 3.6 years were evaluated. A total of 104 (49%) patients received androgen deprivation therapy. Prior to treatment, 52 (25%) patients were on ED medication. Mean doses to the penile bulb, penile crus, and penile shaft were 2490 (IQR: 1529–3656) cGy, 2095 (1306–3036) cGy, and 444 (313–650) cGy, respectively. Fifty-nine (28%) patients had a worsening of ED after treatment. On multivariable analysis, only the mean dose to the penile shaft [OR >345 vs. ≤345: 4.47 (1.43–13.99); p = 0.010] and pretreatment use of ED medication [OR yes vs. no: 12.5 (5.7–27.5; p < 0.001)] predicted for worsening ED. The neural network confirmed that the penile shaft mean dose and pre-treatment ED medication use are the most important factors in predicting ED. Conclusions: Pre-treatment ED and penile shaft dosimetry are important predictors for ED after hypofractionated radiotherapy for prostate cancer.

Black race is associated with increased atopic dermatitis (AD) severity and healthcare resource utilization. However, the burden of out-of-pocket (OOP) expenses among black individuals with AD is not well understood. We sought to characterize the categories and impact of OOP healthcare expenses associated with AD management among black individuals. A 25-question voluntary online survey was administered to National Eczema Association members (N = 113,502). Inclusion criteria (US residents age ≥ 18 years; self-report of AD or primary caregivers of individuals with AD) was met by 77.3% (1118/1447) of respondents. Black individuals with AD were younger, had lower household income, Medicaid, urban residence, poor AD control and frequent skin infections (P ≤ 0.02). Blacks vs. non-blacks reported more OOP costs for prescription medications covered (74.2% vs. 63.6%, P = 0.04) and not covered (65.1% vs. 46.5%, P = 0.0004) by insurance, emergency room visits (22.1% vs. 11.8%, P = 0.005), and outpatient laboratory testing (33.3% vs. 21.8%, P = 0.01). Black race was associated with increased household financial impact from OOP expenses (P = 0.0009), and predictors of financial impact included minimally controlled AD (adjusted OR [95% CI] 13.88 [1.63–117.96], P = 0.02), systemic therapy (4.34 [1.63–11.54], 0.003), > $200 monthly OOP expenses (14.28 [3.42–59.60], P = 0.0003), and Medicaid (4.02 [1.15–14.07], P = 0.03). Blacks with Medicaid had higher odds of harmful financial impact (3.32 [1.77–6.24], P = 0.0002) than those of black race (1.81 [1.04–3.15], P = 0.04) or with Medicaid (1.39 [1.02–1.88], P = 0.04) alone. Black race is associated with increased OOP costs for AD and significant household financial impact. Targeted interventions are needed to address financial disparities in AD.

Reviewer Acknowledgements for International Journal of Statistics and Probability, Vol. 12, No. 3

Reviewer Acknowledgements for International Journal of Statistics and Probability, Vol. 12, No. 2

Emergency tracheostomy is a timely life saving procedure bringing to the fore the expert skills of the difficult airway team comprising the otolaryngologist, anaesthesiologist and theatre team or emergency department staff. Adequate advanced planning has to be adopted in these situations for achieving a good outcome. We present our optimal pathway practiced within our team to achieve successful outcomes during emergency tracheostomies starting from planning to the use of pressure bag in cases of failed intubations.

IntroductionBehavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of intervention-covariate interactions. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups.Methods and analysisSystematic searches of Medline, Embase, CENTRAL, CINAHL, PsycInfo, and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2020 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis (PMA) will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index (BMI) z-score at age 24 +/- 6 months using World Health Organisation Growth Standards, and effect differences will be explored among pre-specified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events.Ethics and disseminationApproved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations, and media releases.RegistrationProspectively registered on PROSPERO: CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis will be the largest individual participant data (IPD) meta-analysis evaluating behavioural interventions for the prevention of early childhood obesity to date, and will provide the most reliable and precise estimates of early intervention effects to inform future decision-making.IPD meta-analysis methodology will enable unprecedented exploration of important individual and trial-level characteristics that may be associated with childhood obesity or that may be effect modifiers.The proposed innovative methodologies are feasible and have been successfully piloted by members of our group.It may not be possible to obtain IPD from all eligible trials; in this instance, aggregate data will be used where available, and sensitivity analyses will be conducted to assess inclusion bias.Outcome measures may be collected and reported differently across included trials, potentially increasing imprecision; however, we will harmonise available data where possible, and encourage those planning or conducting ongoing trials to collect common core outcomes following prospective meta-analysis methodology.

IntroductionLittle is known about how early (e.g., commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to 1) characterise early obesity prevention interventions in terms of target behaviours, delivery features, and behaviour change techniques (BCTs), 2) explore similarities and differences in BCTs used to target behaviours, and 3) explore effectiveness of intervention components in preventing childhood obesity.Methods and analysisAnnual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the TOPCHILD Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components.Ethics and disseminationThe study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations, and targeted communication with key stakeholders.DiscussionOur study will provide an in depth understanding of behavioural components and delivery features used in obesity prevention interventions starting antenatally or in the first 12 months after birth. Understanding common intervention approaches in a systematic way will provide much needed insight to advance the design of early obesity prevention interventions and provide the opportunity to undertake future quantitative predictive modelling.RegistrationPROSPERO registration no. CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis study provides an understanding of behaviours targeted, behaviour change techniques and delivery features used in early childhood obesity prevention trials identified in a systematic review as being eligible for inclusion in the Transforming Obesity Prevention in CHILDren (TOPCHILD) Collaboration.Extends previous methods by coding behaviour change techniques in published and unpublished intervention materials and performing cross validation with trialists through the TOPCHILD Collaboration.Using standardised coding taxonomies will allow for comparisons across studies, and we will pilot test new ontologies from the Human Behaviour Change Project.Explores the complex area of targeting parent and caregivers’ behaviours to impact child outcomes across four key obesity prevention behavioural domains (relating to infant feeding practices, food provision and parent feeding practices, movement practices, sleep health practices).This study will provide preliminary results regarding the examination of intervention components’ effectiveness based on exploratory analysis. Yet, the internationally unique database this project creates will further our understanding of effective intervention components in future research.To date we already have 38 out of 65 eligible trials agreeing to share data, since not all trials may provide unpublished material we may perform sensitivity analyses comparing trials that have shared data to trials that have not shared materials.

Reviewer Acknowledgements for International Journal of Statistics and Probability, Vol. 12, No. 1

Reviewer Acknowledgements for International Journal of Statistics and Probability, Vol. 11, No. 6

Reviewer Acknowledgements for International Journal of Statistics and Probability, Vol. 11, No. 5

Mentoring has become an increasingly popular supportive method for empowering nurses and assisting them to progress in their careers. Evidence from the literature demonstrates that not all experienced and highly qualified nurses are effective mentors. The aim of this study was to explore and describe the experiences of neophyte nurse mentors following their first formal mentoring relationship using a qualitative exploratory design. Data were collected using dual moderated focus group methods. The focus group was digitally recorded and transcribed verbatim. Interviews were analysed using thematic analysis. Six neophyte nurse mentors participated in the focus group. The themes identified included (1) Readiness for mentoring, (2) Venturing into the unknown, (3) Having the right fit (4) Frustrations of mentoring (5) Reciprocal professional relationship. The findings highlight how neophyte nurse mentors perceive mentoring and the importance of providing them with adequate preparation and support in order to efficiently transfer valuable knowledge and skills to their mentees.

Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed. Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA patients in more advanced stages showed further reductions in IL-10 and Tim-3 expression. In conclusion, our results revealed an immunoregulatory disorder in OA independent of obesity, and demonstrated a potential mechanism in establishing the proinflammatory status of OA patients.

Purpose: Respiratory margins for partial breast irradiation (PBI) have been largely based on geometric observations, which may overestimate the margin required for dosimetric coverage. In this study, dosimetric population-based respiratory margins and margin formulas for external beam partial breast irradiation are determined. Methods: Volunteer respiratory data and anterior–posterior (AP) dose profiles from clinical treatment plans of 28 3D conformal radiotherapy (3DCRT) PBI patient plans were used to determine population-based respiratory margins. The peak-to-peak amplitudes (A) of realistic respiratory motion data from healthy volunteers were scaled from A = 1 to 10 mm to create respiratory motion probability density functions. Dose profiles were convolved with the respiratory probability density functions to produce blurred dose profiles accounting for respiratory motion. The required margins were found by measuring the distance between the simulated treatment and original dose profiles at the 95% isodose level. Results: The symmetric dosimetric respiratory margins to cover 90%, 95%, and 100% of the simulated treatment population were 1.5, 2, and 4 mm, respectively. With patient set up at end exhale, the required margins were larger in the anterior direction than the posterior. For respiratory amplitudes less than 5 mm, the population-based margins can be expressed as a fraction of the extent of respiratory motion. The derived formulas in the anterior/posterior directions for 90%, 95%, and 100% simulated population coverage were 0.45A/0.25A, 0.50A/0.30A, and 0.70A/0.40A. The differences in formulas for different population coverage criteria demonstrate that respiratory trace shape and baseline drift characteristics affect individual respiratory margins even for the same average peak-to-peak amplitude. Conclusions: A methodology for determining population-based respiratory margins using real respiratory motion patterns and dose profiles in the AP direction was described. It was found that the currently used respiratory margin of 5 mm in partial breast irradiation may be overly conservative for many 3DCRT PBI patients. Amplitude alone was found to be insufficient to determine patient-specific margins: individual respiratory trace shape and baseline drift both contributed to the dosimetric target coverage. With respiratory coaching, individualized respiratory margins smaller than the full extent of motion could reduce planning target volumes while ensuring adequate coverage under respiratory motion.

Treatment outcome has been associated with dosimetric implant quality assessed in a postplan. Uncertainties during the implant and in the period before postplan evaluation lead to dosimetric deviations from the original treatment plan. The observed range of postplan results can include patients with dosimetry below recommended levels. Further treatment options may be considered to boost the delivered dose and a second seed implant is one way to accomplish this. This work describes the development of a procedure to plan and deliver a second seed implant and an evaluation of the dosimetric improvement. A patient with a post‐plan D90 of 124 Gy was offered a second seed implant 21 weeks after the initial implant. A total dose of 163 Gy was prescribed due to radiobiological considerations for the time between implants. A volume study was performed 2 weeks before the implant and variable angle images of the seeds from the first implant were obtained to reconstruct the original seed coordinates. The second implant was planned considering the total composite physical dose distribution by forward planning additional seeds onto the original implant coordinates. The additional seeds were manually added to a new plan on the volume study images at the planned coordinates and delivered as a typical preplanned implant. Post‐plan evaluation four weeks after the second implant showed a D90 of 177 Gy and a V100 of 92.7%. These results demonstrate the effective use of a second seed implant with image guided composite planning to improve dosimetric implant quality.

Respiratory motion complicates radiotherapy treatment of thoracic and abdominal tumours. Simplified respiratory motions such as sinusoidal and single patient traces are often used to determine the impact of motion on respiratory management techniques in radiotherapy. Such simplifications only accurately model a small portion of patients, as most patients exhibit variability and irregularity beyond these models. We have preformed a comprehensive analysis of respiratory motion and developed a software tool that allows for explicit inclusion of variability. We utilize our realistic respiratory generator to customize respiratory traces to test the robustness of the estimate of internal gross target volumes (IGTV) by 4DCT and CBCT. We confirmed that good agreement is found between 4DCT and CBCT for regular breathing motion. When amplitude variability was introduced the accuracy of the estimate slightly, but the absolute differences were still < 3 mm for both modalities. Poor agreement was shown with the addition of baseline drifts. Both modalities were found to underestimate the IGTV by as much as 30% for 4DCT and 25% for CBCT. Both large and small drifts deteriorated the estimate accuracy. The respiratory trace generator was advantageous for examining the difference between 4DCT and CBCT IGTV estimation under variable motions. It provided useful implementation abilities to test specific attributes of respiratory motion and detected issues that were not seen with the regular motion studies. This is just one example of how the respiratory trace generator can be utilized to test applications of respiratory management techniques.

Summary BacillOndex is an extension of the Ondex data integration system, providing a semantically annotated, integrated knowledge base for the model Gram-positive bacterium Bacillus subtilis. This application allows a user to mine a variety of B. subtilis data sources, and analyse the resulting integrated dataset, which contains data about genes, gene products and their interactions. The data can be analysed either manually, by browsing using Ondex, or computationally via a Web services interface. We describe the process of creating a BacillOndex instance, and describe the use of the system for the analysis of single nucleotide polymorphisms in B. subtilis Marburg. The Marburg strain is the progenitor of the widely-used laboratory strain B. subtilis 168. We identified 27 SNPs with predictable phenotypic effects, including genetic traits for known phenotypes. We conclude that BacillOndex is a valuable tool for the systems-level investigation of, and hypothesis generation about, this important biotechnology workhorse. Such understanding contributes to our ability to construct synthetic genetic circuits in this organism.

Purpose It has been suggested that the Real-time Position Management (RPM) marker block should be placed directly on the breast or sternum to verify deep inspiration breath hold (DIBH) level for breast radiotherapy. We explore three potential issues with this practice: (a) surface dose effect of placing the marker block in the primary beam; (b) effect of marker block tilt on the accuracy of the RPM system; and (c) correlation between marker block positions on the patient surface and internal chest wall position. Methods (a) The surface dose under the two-, four-, and six-dot marker blocks was measured at incident angles of 0° and 30°; (b) the motion amplitude detected when using the two- and six-dot marker blocks was recorded for block tilts from 0° to 60° about the RPM camera line of sight; (c) the correlation between median displacement of the chest wall and median displacement of the surface contour between breath holds was investigated for superior, middle, and inferior block positions using contours extracted from portal images of eight left-sided breast cancer patients. Results (a) The marker blocks increased the surface dose for a 6 MV direct field by 48.2–52.2% of Dmax; (b) at lateral tilts greater than 10°, the two-dot marker block overestimated the motion amplitude; however, the six-dot marker block amplitude remained accurate up to 60°; (c) the whole, superior, and middle surface positions were strongly correlated with chest wall displacement (R2 = 0.83; R2 = 0.90; R2 = 0.83), whereas the inferior position was moderately correlated (R2 = 0.36). Conclusions The RPM marker block can be placed on the breast for DIBH treatments; however, caution should be used regarding surface dose effects. The two-dot marker block should not be used for block tilts beyond 20°. Marker block placement at a middle or superior position on the breast results in the strongest correlation with chest wall position.

Purpose: The authors developed a realistic respiratory trace generating (RTG) tool for use with phantom and simulation studies. Methods: The authors analyzed the extent of abdominal wall motion from a real-time position management system database comprised of 125 lung, liver, and abdominal patients to determine the shape and extent of motion. Using Akaike's information criterion (AIC), the authors compared different model types to find the optimal realistic model of respiratory motion. Results: The authors compared a family of sigmoid curves and determined a four parameter sigmoid fit was optimal for over 98% patient inhale and exhale traces. This fit was also better than sin 2(x) for 98% of patient exhale and 70% of patient inhale traces and better than sin (x) for 100% of both patient inhale and exhale traces. This analysis also shows that sin 2(x) is better than sin (x) for over 95% of patient inhale and exhale traces. With results from shape and extent of motion analysis, we developed a realistic respiratory trace generating (RTG) software tool. The software can be run in two modes: population and user defined. In population mode, the RTG draws entirely from the population data including inter- and intra fraction amplitude and period variability and baseline drift. In user-defined mode, the user customizes the respiratory parameters by inputting the peak-to-peak amplitude, period, end exhale position, as well as controls variability in these parameters and baseline drift. Conclusions: This work provides a method of generating custom respiratory data that can be used for initial implementation and testing of new technologies.

During the 1960s and 1970s, aerial reconnaissance on the northern side of the confluence of the Rivers Trent, Tame, and Mease in Staffordshire revealed a cluster of features indicative of prehistoric ceremonial activity. Some of the features within the cluster are morphologically unique, but a lack of previous investigation meant that their dating, phasing, and function were unknown. This paper details the results of a multi-disciplinary approach to addressing these questions about the complex and to place it into its contemporary landscape context. The results indicate that the complex represents numerous phases of symbolic and ceremonial activity extending from the late Neolithic and into the early Bronze Age. Furthermore, it has shown how these structures fit within a wider landscape of ceremonial activity extending back to the earlier Neolithic and continuing into the Bronze Age.

Purpose: Respiratory motion must be accounted for daily in order to permit optimum radiotherapy of hepatic malignancies. However, existing tracking systems are often invasive or poorly tolerated by patients. The authors describe the development and validation of an ultrasound-guided tracking and gating system for stereotactic body radiation therapy of the liver. Methods: This noninvasive system is designed to determine the correlation between tumor and external fiducial motion and to verify the optimum gating level for treatment delivery daily. A tracked ultrasound probe moves with patient respiration, obtaining 2D ultrasoundimages of tumor motion throughout the respiratory cycle. The target volume is registered to the static radiotherapy treatment beams in order to verify optimum gating levels. These gating levels are then transferred to an existing gating system for treatment delivery. The authors examined the temporal and spatial accuracy of this system using a custom-built phantom and verified the accuracy of gating level transfer and delivery. Results: The temporal accuracy of the ultrasound-guided system was shown to be comparable to the existing clinical x-ray imaging system. Using ultrasound rather than x-rays to image internal targets provides good soft-tissue contrast without the invasiveness of implanting fiducial markers. High frame rates enable continuous monitoring of the target throughout the respiratory cycle. The authors anticipate this passive monitoring system should be well tolerated by patients. Conclusions: The system developed provides good quality video of the laboratory motion phantom and can be successfully used in gated beam delivery.

International audience; Malaysian society is experiencing rapid urbanization and modernization. A sizeable new middle class has emerged and the traditional ways of life and eating habits of the different ethnic communities are changing. For many years, nutritional surveys have been capturing the transformations of food consumptions. To date no comprehensive survey focusing on the socio-cultural determinants of food habits at the national level have been reported. The Malaysian Food Barometer, a nationally representative with follow-up survey, intends to fill this gap. This article presents the conceptual framework and methodologies used to investigate the eating practices and cultural representations on food and eating in a multicultural context. It analyses the influence of modernization on social hierarchies and ethnic cultures, and ultimately on food eating patterns and food styles.La société Malaisienne connaît une rapide urbanisation et un mouvement de modernisation. Une importante classe moyenne a émergé, influençant les styles de vie et les habitudes alimentaires traditionnels des différentes communautés ethniques. Pendant de nombreuses années, des enquêtes nutritionnelles ont permis d’identifier les transformations des consommations alimentaires. Cependant, il n’existait pas à ce jour d’enquête d’envergure sur les déterminants socio-culturels des habitudes alimentaires au niveau national. L'objectif du Baromètre Malaisien de l’Alimentation, qui est une enquête nationale récurrente, est de combler ce vide. Cet article présente le cadre conceptuel et les méthodes utilisées pour enquêter sur les pratiques alimentaires et sur les représentations relatives aux aliments et à l'alimentation dans un contexte multiculturel. Il analyse l'influence de la modernisation sur les hiérarchies sociales, les cultures ethniques et, finalement, sur les habitudes et les styles alimentaires.

BACKGROUND: Practice audit is an important component of continuing professional development that may more readily be undertaken if it were less complex. This qualitative study assessed the use of personal digital assistants to facilitate data collection and review.METHODS: Personal digital assistants programmed with standard questionnaires related to upper gastrointestinal endoscopies (Practice Audit in Gastroenterology-Endoscopy [‘PAGE-Endo’]) and colonoscopies (PAGE-Colonoscopy [‘PAGE-Colo’]) were provided to Canadian gastroenterologists, surgeons and internists. Over a three-week audit period, participants recorded indications, and the expected (E) and reported (R) findings for each procedure. Thereafter, participants recorded compliance with reporting, the ease of use and value of the PAGE program, and their willingness to perform another audit.RESULTS: Over 15 to 18 months, 173 participants completed PAGE-Endo (6168 procedures) and 111 completed PAGE-Colo (4776 procedures). Most respondents noted that PAGE was easy to use (99%), beneficial (88% to 95%), and that they were willing undertake another audit (92% to 95%). In PAGE-Endo, alarm features were prevalent (55%), but major reported findings were less common than expected: esophagitis (E 29.9%, R 14.8%), esophageal stricture (E 8.3%, R 3.6%), gastric ulcer (E 17.0%, R 4.7%), gastric cancer (E 4.3%, R 1.0%) and duodenal ulcer (E 11.5%, R 5.7%). In PAGE-Colo, more colonoscopies were performed for symptom investigation (55%) than for screening (25%) or surveillance (20%). There were marked interprovincial variations with respect to sedation, biopsies and technical aspects of colonoscopy.CONCLUSION: Secure, real-time data entry with review of aggregate and individual data in the PAGE program provided an acceptable, straightforward methodology for accredited practice audit activities. PAGE has considerable potential for continuing professional development in gastroenterology and other specialties.

The use of speckle decorrelation techniques to calculate the displacement of a moving transducer has shown promise. We describe a technique to estimate displacement between pairs of parallel planes without assuming that plane separation in the scan is uniform. We perform theoretical and empirical analyses of the bias and uncertainty in plane spacing estimates as a function of speckle size, patch size, and the number of planes used for normalization. Practically, only the central, linear region of the autocovariance curves can be used in this decorrelation method, which implies that distance between acquired image planes should be approximately half the speckle size. In this region, the uncertainty in estimated plane spacing was less than 15% for a 8.1 mm (axial) by 9.1 mm (lateral) patch and increased to 33% for an 8.1 mm (axial) by 1.5 mm (lateral) patch. The number of planes, Nz, used to calculate the normalization factors (averages of brightness and- squared brightness) was a major source of bias. Optimum Nz was found to be five to ten planes, depending on distance between acquired image planes, with a poor choice of Nz resulting in a bias of 10% or greater. A second source of bias is brightness gradients which, although they appear very slight on intensity images, can cause a large bias is the plane spacing estimates made using linearized data.

We present a practical, generic, easy-to-use framework for the implementation of new radiation therapy technologies and treatment techniques in low-income countries. The framework is intended to standardize the implementation process, reduce the effort involved in generating an implementation strategy, and provide improved patient safety by reducing the likelihood that steps are missed during the implementation process. The 10 steps in the framework provide a practical approach to implementation. The steps are, 1) Site and resource assessment, 2) Evaluation of equipment and funding, 3) Establishing timelines, 4) Defining the treatment process, 5) Equipment commissioning, 6) Training and competency assessment, 7) Prospective risk analysis, 8) System testing, 9) External dosimetric audit and incident learning, and 10) Support and follow-up. For each step, practical advice for completing the step is provided, as well as links to helpful supplementary material. An associated checklist is provided that can be used to track progress through the steps in the framework. While the emphasis of this paper is on addressing the needs of low-income countries, the concepts also apply in high-income countries.

Aims: This study investigated the competitive abilities of two Neocallimastix patriciarum-derived xylanases constructs in Butyrivibrio fibrisolvens H17c (xynA and pUMSX) and their ability to compete in vivo. Methods and Results: The digestibility of neutral detergent fibre (NDF) increased during co-culture of xynA or pUMSX and weakly cellulolytic, but not with highly cellulolytic, ruminococci. Competition studies among xynA, pUMSX and cellulolytic consortia demonstrated that xynA was the fittest. XynA did not persist at high levels in the rumen and was undetectable after 22 days. Conclusions: The construction of recombinant xylanolytic B. fibrisolvens does improve the digestibility of fibre above that of the native, but digestibility is still less than that of the most potent fibre digesters such as ruminococci. Significance and Impact of the Study: Fibre digestion may be improved by genetic manipulation of ruminal bacteria but ecological parameters, such as persistence in vivo and the niche of the organism, must be taken into account.

A novel pathway for degradation of the cyanobacterial heptapeptide hepatotoxin microcystin LR was identified in a newly isolated Sphingomonas sp. (Bourne et al. 1996 Appl. Environ. Microbiol. 62: 4086-4094). We now report the cloning and molecular characterisation of four genes from this Sphingomonas sp. that exist on a 5.8-kb genomic fragment and encode the three hydrolytic enzymes involved in this pathway together with a putative oligopeptide transporter. The heterologously expressed degradation pathway proteins are enzymatically active. Microcystinase (MlrA), the first enzyme in the degradative pathway, is a 336-residue endopeptidase, which displays only low sequence identity with a hypothetical protein from Methanobacterium thermoautotrophicum. Inhibition of microcystinase by EDTA and 1,10-phenanthroline suggests that it is a metalloenzyme. The most likely residues that could potentially chelate an active-site transition metal ion are in the sequence HXXHXE, which would be unique for a metalloproteinase. Situated immediately downstream of mlrA with the same direction of transcription is a gene mlrD, whose conceptual translation (MlrD, 442 residues) shows significant sequence identity and similar potential transmembrane spanning regions to the PTR2 family of oligopeptide transporters. A gene mlrB is situated downstream of the mlrA and mlrD genes, but transcribed in the opposite direction. The gene encodes the enzyme MlrB (402 residues) which cleaves linear microcystin LR to a tetrapeptide degradation product. This enzyme belongs to the "penicillin-binding enzyme" family of active site serine hydrolases. The final gene in the cluster mlrC, is located upstream of the mlrA gene and is transcribed in the opposite direction. It codes for MlrC (507 residues) which mediates further peptidolytic degradation of the tetrapeptide. This protein shows significant sequence identity to a hypothetical protein from Streptomyces coelicolor. It is suspected to be a metallopeptidase based on inhibition by metal chelators. It is postulated on the basis of comparison with other microorganisms that the genes in this cluster may all be involved in cell wall peptidoglycan cycling and subsequently act fortuitously in hydrolysis of microcystin LR.

The purpose of this study was to determine whether an in-hospital transportable CT scanner can provide diagnostic brain images and to compare the quality of these images with those from a conventional fixed-platform CT scanner.Twenty-seven patients with known or suspected intracranial pathology underwent imaging on a transportable scanner and a fixed-platform scanner within 1 hr of each other. Images from each CT examination were evaluated independently by two neuroradiologists who were unaware of patient history. Conspicuousness of intracranial pathology and normal anatomy were rated on a 5-point scale (1 point, optimal; 5 points, poor or not visualized). Statistical comparisons were made using nonparametric tests.Seven CT scans were interpreted as showing normal findings and 20 scans revealed intracranial pathology on both CT scanners. Image quality was higher on the fixed scanner (average rating, 2.42 points; SE = .12) than on the transportable scanner (average rating, 3.10 points; SE = .12) (p = .001). Depiction of the cerebellum, midbrain, and supratentorial gray-white matter was better on the fixed scanner (p.05). However, we found no significant differences in detection of intracranial pathology between scanners. Both radiologists found images from both scanners to be diagnostic in all 27 patients.Images of the brain on the transportable CT scanner were less clear than those on a fixed scanner. However, images from the transportable CT scanner were diagnostic in 27 consecutive patients. The implications of this finding are important for the provision of CT services for critically ill patients who cannot be transported to the radiology department.

Twenty-three strains of Ruminococcus isolated from ruminants were assessed for digestive ability on different plants and purified cellulose. Genetic diversity was assessed by ERIC, REP and 16–23S rDNA spacer polymorphisms. All ruminococci could be typed by ERIC, REP or 16–23S rDNA spacer, but all three typing methods had to be used in concert to differentiate closely related strains. Digestibility of lucerne (Medicago sativa), rhodes grass (Chloris gayana) and spear grass (Heteropogon contortus) were assessed. Dry matter (DM) digestibility was highly correlated (> 0·93) with neutral detergent fibre (NDF) digestibility, but cellulose disc digestibility was a poor indicator of DM and NDF digestibility. Studies demonstrate the wide variation in ability of ruminococci to digest forages, and some recently isolated strains (Y1, LP-9155, AR67, AR71 and AR72) were superior to reference strains (FD-1 and Ra8). Multivariate analysis showed that groupings derived from genotyping data closely resembled those determined by digestibility data. This study indicated that ruminococci are diverse in digestive ability and genotype, and this diversity suggests that there may be highly fibrolytic strains in nature that could be utilized for animal production.

Multiple sclerosis (MS) is a T cell-mediated autoimmune demyelinating disease1, which may be initiated by a virus infection2. Theiler's murine encephalomyelitis virus (TMEV), a natural mouse pathogen, is a picornavirus that induces a chronic, CD4+ T cell-mediated demyelinating disease with a clinical course and histopathology similar to that of chronic progressive MS (ref. 3). Demyelination in TMEV-infected mice is initiated by a mononu-clear inflammatory response mediated by virus-specific CD4+ T cells targeting virus, which chronically persists in the CNS (ref. 4–6). We show that beginning 3–4 weeks after disease onset, T-cell responses to multiple myelin autoepitopes arise in an ordered progression and may play a pathologic role in chronic disease. Kinetic and functional studies show that T-cell responses to the immunodominant myelin proteolipid protein epitope (PLP139–151) did not arise because of cross-reactivity between TMEV and self epitopes (that is, molecular mimicry)7, 8, but because of de novo priming of self-reactive T cells to sequestered autoantigens released secondary to virus-specific T cell-mediated demyelination (that is, epitope spreading)9, 10. Epitope spreading is an important alternate mechanism to explain the etiology of virus-induced organ-specific autoimmune diseases.

Purpose: We investigate DIBH breast radiotherapy using the Real-time Position Management (RPM) system with the marker-block placed on the target breast or chest wall. Methods: We measured surface dose for three different RPM marker-blocks using EBT3 Gafchromic film at 0° and 30° incidence. A registration study was performed to determine the breast surface position that best correlates with overall internal chest wall position. Surface and chest wall contours from MV images of the medial tangent field were extracted for 15 patients. Surface contours were divided into three potential marker-block positions on the breast: Superior, Middle, and Inferior. Translational registration was used to align the partial contours to the first-fraction contour. Each resultant transformation matrix was applied to the chest wall contour, and the minimum distance between the reference chest wall contour and the transformed chest wall contour was evaluated for each pixel. Results: The measured surface dose for the 2-dot, 6-dot, and 4-dot marker-blocks at 0° incidence were 74%, 71%, and 77% of dose to dmax respectively. At 30° beam incidence this increased to 76%, 72%, and 81%. The best external surface position was patient and fraction dependent, with no consistent best choice. Conclusions: The increase in surface dose directly under the RPM block is approximately equivalent to 3 mm of bolus. No marker-block position on the breast surface was found to be more representative of overall chest wall motion; therefore block positional stability and reproducibility can be used to determine optimal placement on the breast or chest wall.

The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment. The American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery has developed appropriate use criteria for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered based on tumor and patient characteristics. This document reflects the rating of appropriateness of MMS for each of these clinical scenarios by a ratings panel in a process based on the appropriateness method developed by the RAND Corp (Santa Monica, CA)/University of California–Los Angeles (RAND/UCLA). At the conclusion of the rating process, consensus was reached for all 270 (100%) scenarios by the Ratings Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46 (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34 inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2 inappropriate. These appropriate use criteria have the potential to impact health care delivery, reimbursement policy, and physician decision making on patient selection for MMS, and aim to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest. In addition, recognition of those scenarios rated as uncertain facilitates an understanding of areas that would benefit from further research. Each clinical scenario identified in this document is crafted for the average patient and not the exception. Thus, the ultimate decision regarding the appropriateness of MMS should be determined by the expertise and clinical experience of the physician.

Background Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly Lucilia cuprina are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance. Results The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores. Conclusions We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.

Murphy TP, Dorfman GS, Esparza AR, Duwaji MS, Smith WJ. Arteriosclerosis obliterans in a rabbit model. Invest Radiol 1992;27:1059–1063. RATIONALE AND OBJECTIVES. The authors induced atherosclerotic occlusions in a rabbit model, using and comparing different experimental methods. METHODS. Lesions were induced in 40 femoral arteries in 20 rabbits. Four combinations of lesion induction methods were used: 1) drying of the endothelium with carbon dioxide gas; 2) gas-drying of the artery plus mechanical injury; 3) gas-drying plus induced thrombosis of the treated segment using thrombin; and 4) gas-drying, mechanical injury, and induced throm bosis. All rabbits were fed a high-fat, high-cholesterol diet for 1 to 2 months after lesion induction. RESULTS. Seventeen rabbits were available for follow-up. Sixty-eight percent (13 of 19) of femoral arteries treated with thrombin-induced thrombosis demonstrated atherosclerotic occlusions, compared with 27% of those that did not receive this treatment (4 of 15; P CONCLUSIONS. Thrombin-induced thrombotic occlusion of a segment of artery which has been de-endothelialized, followed by a high-fat, high-cholesterol diet, results in a higher yield of experimental occlusive atherosclerosis in rabbits than is achievable by other methods.

Crude extracts of Babesia bovis parasites were shown to induce levels of protection in susceptible cattle equivalent to that resulting from natural infection. The crude material was systematically fractionated and tested in numerous sequential vaccination/challenge experiments in adult cattle. Antigens in protective fractions were then purified by affinity chromatography with monoclonal antibodies. Three highly protective (more than 95% reduction in parasitaemias) antigens were thus identified. None of these antigens was immunodominant; a number of immunodominant antigens were identified and all were immunosuppressive and/or non-protective. The three protective antigens were cloned and expressed as either beta-galactosidase or glutathione-S-transferase (GST) fusion proteins. Two of these, GST-12D3 and GST-11C5, when used in combination were almost as protective as has been previously shown for the commercially available live attenuated vaccine. A short fragment of a third antigen (21B4) has also been shown to be protective. In two of the antigens, repetitive segments have been shown to be non-protective while the third antigen (12D3) does not contain repetitive domains. Homologues of these antigens exist in other Babesia species and it is anticipated that these may be candidate antigens for protective vaccines against those species.

This communication deals only with the procedure used for the extraction and analysis of the ionic herbicices. Essentially, the wipe sample extraction involved the use of a potassium hydroxide. Extractions were performed in a heated sonic bath to facilitate hydrolysis of any ester forms of the herbicides studied. Following this extraction/hydrolysis, the alkali solution was washed first with petroleum ether and then with diethyl ether to remove possible interferences from nonionic pesticides and other contaminants. The next steps involved acidification of the sample and then extraction of the herbicide acids with diethyl ether. The ether extracts was dried over acidified sodium sulfate, concentrated, methylated, and analyzed by electron-capture gas chromatography

Purpose This study quantifies errors associated with MR-guided High Dose Rate (HDR) gynecological brachytherapy. Uncertainties in this treatment results from contouring, organ motion between imaging and treatment delivery, dose calculation, and dose delivery. We focus on interobserver and inter-modality variability in contouring and the motion of organs at risk (OARs) in the time span between the MR and CT scans (∼1 hour). We report the change in organ volume and position of center of mass (CM) between the two imaging modalities. Methods A total of 8 patients treated with MR-guided HDR brachytherapy were included in this study. Two observers contoured the bladder and rectum on both MR and CT scans. The change in OAR volume and CM position between the MR and CT imaging sessions on both image sets were calculated. Results The absolute mean bladder volume change between the two imaging modalities is 67.1cc. The absolute mean inter-observer difference in bladder volume is much lower at 15.5cc (MR) and 11.0cc (CT). This higher inter-modality volume difference suggests a real change in the bladder filling between the two imaging sessions. Change in Rectum volume inter-observer standard error of means (SEM) is 3.18cc (MR) and 3.09cc (CT), while the inter-modality SEM is 3.65cc (observer 1), and 2.75cc (observer 2). The SEM for rectum CM position in the superior-inferior direction was approximately three times higher than in other directions for both the inter—observer (0.77 cm, 0.92 cm for observers 1 and 2, respectively) and inter-modality (0.91 cm, 0.95 cm for MR and CT, respectively) variability. Conclusion Bladder contours display good consistency between different observers on both CT and MR images. For rectum contouring the highest inconsistency stems from the observers’ choice of the superior-inferior borders. A complete analysis of a larger patient cohort will enable us to separate the true organ motion from the inter-observer variability.

Purpose: We used Real-Time Position Management (RPM) to evaluate breath hold amplitude and variability when gating with a visually monitored deep inspiration breath hold technique (VM-DIBH) with retrospective cine image chest wall position verification. Methods: Ten patients with left-sided breast cancer were treated using VM-DIBH. Respiratory motion was passively collected once weekly using RPM with the marker block positioned at the xiphoid process. Cine images on the tangent medial field were acquired on fractions with RPM monitoring for retrospective verification of chest wall position during breath hold. The amplitude and duration of all breath holds on which treatment beams were delivered were extracted from the RPM traces. Breath hold position coverage was evaluated for symmetric RPM gating windows from ± 1 to 5 mm centered on the average breath hold amplitude of the first measured fraction as a baseline. Results: The average (range) breath hold amplitude and duration was 18 mm (3–36 mm) and 19 s (7–34 s). The average (range) of amplitude standard deviation per patient over all breath holds was 2.7 mm (1.2–5.7 mm). With the largest allowable RPM gating window (± 5 mm), 4 of 10 VM-DIBH patients would have had ≥ 10% of their breath holdmore » positions excluded by RPM. Cine verification of the chest wall position during the medial tangent field showed that the chest wall was greater than 5 mm from the baseline in only 1 out of 4 excluded patients. Cine images verify the chest wall/breast position only, whether this variation is acceptable in terms of heart sparing is a subject of future investigation. Conclusion: VM-DIBH allows for greater breath hold amplitude variability than using a 5 mm gating window with RPM, while maintaining chest wall positioning accuracy within 5 mm for the majority of patients.« less

Pregnant women have an increased risk of influenza infection and complications. The Advisory Committee on Immunization Practices currently recommends vaccination for women who are pregnant during influenza season. The authors review the literature concerning influenza vaccine safety, effectiveness, and coverage rates during pregnancy, as well as opportunities to improve vaccination rates during pregnancy. No study has demonstrated an increased risk of maternal complications or adverse fetal outcomes associated with inactivated influenza vaccine. Few studies have examined the effectiveness of vaccination during pregnancy, and the results from these studies are inconsistent, with some showing a protective effect and others showing no effect. Despite the proven safety of vaccination and the possible benefits to women and their infants, reported vaccination rates during pregnancy are generally less than 10%. Mothers frequently cite concerns about vaccine safety as a barrier to vaccination. Lack of adequate information about the risks and benefits of vaccination is reported by both patients and obstetric care providers. Organizational factors such as lack of vaccine storage facilities may also limit vaccination during pregnancy. Effective interventions should target factors pertaining to patients or providers, or they should address organizational or logistic barriers. The Advisory Committee on Immunization Practices currently recommends standing orders programs or reminders for patients and providers as strategies to improve vaccination rates.

Swallowed or inhaled partial dentures can present a diagnostic challenge. Three new cases are described, one of them near-fatal because of vascular erosion and haemorrhage. The published work points to the importance of good design and proper maintenance. The key to early recognition is awareness of the hazard by denture-wearers, carers and clinicians.

Purpose: Gated radiotherapy is used to reduce internal motion margins, escalate target dose, and limit normal tissue dose; however, its temporal accuracy is limited. Beam-on and beam-off time delays can lead to treatment inefficiencies and/or geographic misses; therefore, AAPM Task Group 142 recommends verifying the temporal accuracy of gating systems. Many groups use sinusoidal phantom motion for this, under the tacit assumption that use of sinusoidal motion for determining time delays produces negligible error. The authors test this assumption by measuring gating time delays for several realistic motion shapes with increasing degrees of irregularity. Methods: Time delays were measured on a linear accelerator with a real-time position management system (Varian TrueBeam with RPM system version 1.7.5) for seven motion shapes: regular sinusoidal; regular realistic-shape; large (40%) and small (10%) variations in amplitude; large (40%) variations in period; small (10%) variations in both amplitude and period; and baseline drift (30%). Film streaks of radiation exposure were generated for each motion shape using a programmable motion phantom. Beam-on and beam-off time delays were determined from the difference between the expected and observed streak length. Results: For the system investigated, all sine, regular realistic-shape, and slightly irregular amplitude variation motions had beam-off andmore » beam-on time delays within the AAPM recommended limit of less than 100 ms. In phase-based gating, even small variations in period resulted in some time delays greater than 100 ms. Considerable time delays over 1 s were observed with highly irregular motion. Conclusions: Sinusoidal motion shapes can be considered a reasonable approximation to the more complex and slightly irregular shapes of realistic motion. When using phase-based gating with predictive filters even small variations in period can result in time delays over 100 ms. Clinical use of these systems for patients with highly irregular patterns of motion is not advised due to large beam-on and beam-off time delays.« less

Partial breast irradiation (PBI) following breast-conserving surgery is emerging as an effective means to achieve local control and reduce irradiated breast volume. Patients are planned on a static CT image; however, treatment is delivered while the patient is free-breathing. Respiratory motion can degrade plan quality by reducing target coverage and/or dose homogeneity. A variety of methods can be used to determine the required margin for respiratory motion in PBI. We derive geometric and dosimetric respiratory 1D margin. We also verify the adequacy of the typical 5 mm respiratory margin in 3D by evaluating plan quality for increasing respiratory amplitudes (2–20 mm). Ten PBI plans were used for dosimetric evaluation. A database of volunteer respiratory data, with similar characteristics to breast cancer patients, was used for this study. We derived a geometric 95%-margin of 3 mm from the population respiratory data. We derived a dosimetric 95%-margin of 2 mm by convolving 1D dose profiles with respiratory probability density functions. The 5 mm respiratory margin is possibly too large when 1D coverage is assessed and could lead to unnecessary normal tissue irradiation. Assessing margins only for coverage may be insufficient; 3D dosimetric assessment revealed degradation in dose homogeneity is the limiting factor,more » not target coverage. Hotspots increased even for the smallest respiratory amplitudes, while target coverage only degraded at amplitudes greater than 10 mm. The 5 mm respiratory margin is adequate for coverage, but due to plan quality degradation, respiratory management is recommended for patients with respiratory amplitudes greater than 10 mm.« less

In gated radiotherapy, the accuracy of treatment delivery is determined by the accuracy with which both the imaging and treatment beams are gated. The time delay is the time between when the markers enter or leave the specified position range for amplitude based gating, or phase for phase based gating, and when an image is obtained or linear accelerator beam starts or ceases delivery. We measured time delay for three fluoroscopy systems and three linear accelerator treatment beams, varying gating type (amplitude vs. phase), beam energy, dose rate, and period. In the system we studied, the treatment beam was turned on and off later than expected by 0.08 ± 0.03s (1 SD). Retrospectively gated fluoroscopy systems had time delays in the opposite direction, indicating the images appeared to have been acquired earlier than they had in reality. The average beam on imaging time delays were −0.04 ± 0.05s (amplitude,), −0.11 ± 0.04s (phase); while the average beam off imaging time delays were −0.18 ± 0.08s (amplitude) and −0.15 ± 0.04s (phase). In this case, the asynchronous time delays for the imaging and treatment systems add linearly. We measure and model the effect of asynchronous time delays on gated deliveries and discuss their implications.

Purpose: Many centers are looking beyond conventional wedged tangential fields for the treatment of breast cancer by using intensity modulation techniques for improvements in the dose distribution, reduced late tissue toxicity, and improved cosmesis. The improvement in dose uniformity may be mitigated in the presence of respiratory motion. We have compared a forward planned intensity modulated technique with a conventional wedged tangent approach for irradiation of the whole breast. The purpose of this study was to compare these techniques under both static and dynamic conditions to simulate the effect of respiratory motion. Method and Materials: We planned these two techniques (conventional wedged tangents and forward planned intensity modulated) on a stationary beeswax breast phantom containing a cork lung insert, using a CT acquired 3D dataset. Treatments were performed with the phantom stationary, and mounted on a moving platform having a sinusoidal waveform. The resulting dose distributions were measured using radiographic film in the anterior‐posterior (AP) and medial‐lateral (ML) directions. The amplitude of motion and angle of tilt of the breast, representing the relative contributions of the cranio‐caudal (CC) and AP components of breathing motion, were varied. Results: The dose distributions for the conventional and forward planned techniques were not significantly affected by motion in both the CC and ML directions, for 1cm and 2cm amplitude, and tilt angles of 15, 30 or 45 degrees. This can be explained as the majority of dose is delivered through open fields, with only a small modulation component using MLCs for forward planning. Conclusion: This study demonstrates negligible differences in dose distribution with conventional and simple forward‐planned IMRT techniques. The dosimetric benefits of forward planned 3D compensated breast radiotherapy are not adversely affected by respiratory motion.

Purpose: The accuracy of treatment delivery in gated radiotherapy depends on time delays between target entry into the gated region and beam‐on, as well as target exit from the gated region and beam‐off. This study measures time delays, extending past work with simple sinusoidal motion to more realistic breath motions. Methods: The setup consisted of two platforms moving synchronously, programmed with realistic breathing motion. The vertical platform supported an infrared marker block, tracked by the Varian Truebeam Real‐time Position Management system. The horizontal platform supported an x‐ray sensitive film with a copper sheet for build‐up. A stationary cone mounted above the film defined a spot, translated into streaks by the moving platform. These film streaks were measured to determine the treatment‐beam delivery time, based on the speed of the platform. Time delays were determined from differences between the duration of the gating window and treatment‐beam delivery time. To discriminate beam‐on and beam‐off time delays, either the start or the end of the gating window coincided with a stable point of motion. Time delays were measured for different beam energies and motion patterns. Results: At 6MV beam energy, beam‐on time delay was significantly longer (p=0.01) for realistic (mean±SEM of 172±8 ms) than for sinusoidal (mean±SEM of 133±3 ms) motion and beam‐off time delay was significantly longer (p=0.05) for realistic (mean±SEM of 83±6 ms) than for sinusoidal (mean±SEM of 64±4 ms) motion. 15 MV results were consistent for beam‐on and beam‐off delays. The observed late time delays can Results: in treatment inefficiency (beam‐on delays) or, more importantly, to geographical miss (beam‐off delays). Conclusion: The shape of breath motions may be a significant factor determining the time delay. These preliminary findings suggest that the use of sinusoidal motion may underestimate time delays. Further work is needed to determine if sinusoidal motion is sufficient.

Purpose: IMRT and partial breast irradiation (PBI) are used to improve cosmetic outcomes in early stage breast cancer patients; however, homogeneity and dose coverage are degraded by respiratory motion during delivery. We investigate the impact of respiratory motion on PBI IMRT using population respiratory data. Methods: The fluences from five different PBI IMRT plans were convolved with a population probability density function (PDF) to simulate dose delivery during respiration. Plan quality and coverage of the CTVsu (CTV plus 5 mm set‐up margin, trimmed back from skin and chestwall) were evaluated using DVH, hotspot, cold spot, and uniformity index. Results: All plans showed blurring (loss of coverage) in the shoulder region of the DVH curves for CTVsu and increased hotspot to the ipsilateral breast. For the patient with the largest breast volume and the smallest DEV:breast volume ratio, the CTVsu is surrounded by tissue. In this patient, the CTVsu coverage is slightly degraded and the hot spot becomes slightly hotter. The patients with a target volume near skin, lung or severe contour changes experience coverage loss near inhomogeneities and increased hot spots. This occurs for trimmed DEVs, although flash was added appropriately to all plans and coverage to the PTV (not only DEV) is adequate in the original plan. In patients with small breasts the CTVsu was noticeably hotter under respiratory conditions than static with the hot spot (2cc) in the CTVsu increasing by 7% and the 95% coverage increasing by 2%. Conclusions: The impact of respiratory motion on PBI is nontrivial and mainly patient dependent. Breast and target shape are the major determining factors in degradation of plan quality with respiration.

In the current climate of Medical Physics employment, establishing an entry-level position may be a daunting task for all individuals seeking to enter the profession. Whether enrolled in a CAMPEP-accredited graduate program or transitioning from a related field of study, the pathways into Medical Physics have become narrow and competitive. The purpose of this meeting is to summarize available post-graduate training opportunities en route to ABR certification. Our distinguished speakers will also be happy to answer general questions and address the major concerns of all students and trainees in attendance.