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For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression., (© 2024 UICC.)

Background: The Placebo-controlled Trial of Percutaneous Coronary Intervention for the Relief of Stable Angina (ORBITA-2) provided evidence for the role of percutaneous coronary intervention (PCI) for angina relief in stable coronary artery disease (CAD). Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are often used to guide PCI, however their ability to predict placebo-controlled angina improvement is unknown., Methods: Participants with angina, ischemia, and stable CAD were enrolled and antianginal medications were stopped. Participants reported angina episodes daily for 2 weeks using the ORBITA-app. At the research angiogram, FFR and iFR were measured. After sedation and auditory isolation, participants were randomized to PCI or placebo, before entering a 12-week blinded follow-up phase with daily angina reporting. The ability of FFR and iFR, analyzed as continuous variables, to predict the placebo-controlled effect of PCI, was tested using Bayesian proportional odds modelling., Results: Invasive physiology data were available in 279 patients (140 PCI and 139 placebo). The median (IQR) age was 65 years (59.0 to 70.5) and 223 (79.9%) were male. Median FFR was 0.60 (0.46 to 0.73) and median iFR was 0.76 (0.50 to 0.86). The lower the FFR or iFR, the greater the placebo-controlled improvement with PCI across all endpoints. There was strong evidence that a patient with an FFR at the lower quartile would have a greater placebo-controlled improvement in angina symptom score with PCI than a patient at the upper quartile (FFR 0.46 vs. 0.73: OR 2.01, 95% CrI 1.79 to 2.26, Pr(Interaction)>99.9%). Similarly, there was strong evidence that a patient with an iFR at the lower quartile would have a greater placebo controlled improvement in angina symptom score with PCI than a patient with an iFR at the upper quartile (iFR 0.50 vs. 0.86: OR 2.13, 95% CrI 1.87 to 2.45, Pr(Interaction) >99.9%). The relationship between benefit and physiology was seen in both Rose angina and Rose nonangina., Conclusions: Physiological stenosis severity, as measured by FFR and iFR, predicts placebo-controlled angina relief from PCI. Invasive coronary physiology can be used to target PCI to those patients who are most likely to experience benefit.

Background: Placebo-controlled evidence from ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) found that percutaneous coronary intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many patients. The reason for this was unclear., Objectives: This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, noninvasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI., Methods: Prerandomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the World Health Organization Rose angina questionnaire (Rose). Disease severity was assessed using quantitative coronary angiography, stress echocardiography, fractional flow reserve, and instantaneous wave-free ratio. Bayesian ordinal regression was used., Results: At prerandomization, the median number of daily angina episodes was 0.8 (Q1-Q3: 0.4-1.6), 64% had Rose angina, quantitative coronary angiography diameter stenosis was 61% (Q1-Q3: 49%-74%), stress echocardiography score was 1.0 (Q1-Q3: 0.0-2.7), fractional flow reserve was 0.63 (Q1-Q3: 0.49-0.75), and instantaneous wave-free ratio was 0.78 (Q1-Q3: 0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with quantitative coronary angiography ordinal correlation coefficient: 0.06 (95% credible interval [CrI]: 0.00-0.08); stress echocardiography: 0.09 (95% CrI: 0.02-0.10); fractional flow reserve: 0.04 (95% CrI: -0.03 to 0.07); and instantaneous wave-free ratio: 0.04 (95% CrI: -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR: 1.9; 95% CrI: 1.6-2.1; probability of interaction [Pr Interaction ] = 99.9%; and OR: 1.8; 95% CrI: 1.6-2.1; Pr Interaction  = 99.9%, respectively)., Conclusions: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI., Competing Interests: Funding Support and Author Disclosures ORBITA-2 was an investigator-initiated trial sponsored by Imperial College London. The trial was funded by grants from National Institute for Health and Care Research Imperial Biomedical Research Centre, Medical Research Council, British Heart Foundation, National Institute for Health and Care Research, and the Imperial Coronary Flow Trust. Philips Volcano supplied the coronary pressure wires. Dr Simader has received a sponsorship from Servier Pharmaceuticals. Dr Rajkumar has received speaker fees from Menarini; and has received consulting fees from Philips. Dr Foley has received speaker fees from Menarini and Philips. Dr Khokhar has received speaker fees and travel support from Boston Scientific and Abbott. Dr Davies has received grants from Medtronic and Abbott; has received sponsorship from Vascular Perspectives, Boston Scientific, Medtronic and Abbott; and has received speaker fees from AstraZeneca, Pfizer, Bristol Myers Squibb, and Novartis. Dr Keeble has served on advisory boards for Abbott Vascular and SMT; and has received institutional research funding from Terumo, Medtronic, Boston Scientific, Abbott Vascular, Philips Volcano, and Cardionovum. Dr O’Kane has received speaker fees from Abbott Vascular, Biosensors, Boston Scientific, Heartflow, Medtronic, Philips, Shockwave, and Terumo. Dr Kotecha has received honoraria from Bayer and Janssen. Dr Nijjer has received speaker fees from Philips Volcano, Pfizer, Bayer, AstraZeneca, Boehringer Ingelheim, and Amarin. Dr Spratt has received speaker fees from Boston Scientific Corporation and Shockwave Medical, Inc. Dr Sen has received speaker and consulting fees from Philips, Medtronic, Recor, and AstraZeneca. Dr Curzen has received grants from Beckman Coulter, Inc, Boston Scientific Corporation, Haemonetics Corporation, and HeartFlow Inc; and has received speaker fees from Heartflow. Dr Howard has received shares in Mycardium AI; and has received a grant from the British Heart Foundation. Dr Cole has received shares in Mycardium AI. Dr Al-Lamee has served on advisory boards for Janssen Pharmaceuticals, Abbott, and Philips; and has received speaker fees from Abbott, Philips, Medtronic, Servier, Omniprex, and Menarini. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: In stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in fact, angina., Objectives: This study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI)., Methods: ORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from -10 (placebo replicated the symptom more than balloon occlusion) to +10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI., Results: Fifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95% credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95% credible interval: 0.71-1.99), Pr (difference) >99.9%., Conclusions: Similarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of Angina Assessment Before Revascularization [ORBITA-STAR]; NCT04280575)., Competing Interests: Funding Support and Author Disclosures This work has received support from the National Institute for Health and Care Research Imperial Biomedical Research Centre and the Imperial College British Heart Foundation Centre of Research Excellence. Dr Rajkumar has received a Clinical Research Training Fellowship from the Medical Research Council; has received speaker fees from Menarini; and has received consulting fees from Philips. Dr Foley has received a Clinical Research Training Fellowship from the Medical Research Council; and has received speaker fees from Menarini and Philips. Dr Ahmed-Jushuf has received a Clinical Research Training Fellowship from the Medical Research Council. Dr Simader has received sponsorship from Servier. Dr Sen has received speaker and consulting fees from Philips, Medtronic, Recor, and AstraZeneca. Dr Petraco has received consulting fees from Philips and Abbott. Dr Nijjer has received speaker fees from Philips Volcano, Pfizer, Bayer, AstraZeneca, Boehringer Ingelheim, and Amarin. Dr Dungu has received grants from Medtronic and Abbott; has received sponsorship from Vascular Perspectives, Boston Scientific, Medtronic, and Abbott; and has received speaker honoraria from AstraZeneca, Pfizer, Bristol Myers Squibb, and Novartis. Dr Kotecha has received honoraria from Bayer and Janssen. Dr Cole holds shares in Mycardium AI. Dr Howard holds shares in Mycardium AI. Dr Keeble has served on the advisory boards of Abbott Vascular and SMT; and has received institutional research funding from Terumo, Medtronic, Boston Scientific, Abbott Vascular, Philips Volcano, and Cardionovum. Dr O’Kane has received speaker fees from Abbott Vascular, Biosensors, Boston Scientific, HeartFlow, Medtronic, Philips, Shockwave, and Terumo. Dr Al-Lamee has received an Intermediate Research Fellowship from the British Heart Foundation [FS/ICRF/22/26051]; has served on the advisory boards of Janssen Pharmaceuticals, Abbott, and Philips; and has received speaker honoraria from Abbott, Philips, Medtronic, Servier, Omniprex, and Menarini. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: The Montreal Cognitive Assessment (MoCA) is recommended by the Movement Disorder Society for cognitive testing in movement disorders including Parkinson's disease (PD) and lewy body dementia. Few studies have compared cognitive screening instruments in these diseases, which overlap clinically., Objective: To compare the MoCA and Quick Mild Cognitive Impairment (Q mci) screen in this population., Methods: Patients attending memory and movement disorder clinics associated with a university hospital had the MoCA and Q mci screen performed and diagnostic accuracy compared with the area under the receiver operating characteristic curve (AUC). Duration and severity of movement disorders was assessed using the Unified PD Rating Scale (UPDRS)., Results: In total, 133 assessments were available, median age 74±5. Median education was 11±4 years and 65% were male. Median total UPDRS score was 37±26. Median Q mci screen was 51±27, median MoCA was 19±10. There were statistically significant differences in test scores between those with subjective symptoms but normal cognition, mild cognitive impairment (MCI) and dementia ( p  < 0.001). The Q mci screen had significantly greater accuracy differentiating normal cognition from MCI versus the MoCA (AUC 0.90 versus 0.72, p  = 0.01). Both instruments had similar accuracy in identifying cognitive impairment and separating MCI from dementia. The median administration time for the Q mci screen and MoCA were 5.19 and 9.24 minutes ( p  < 0.001), respectively., Conclusions: Both the MoCA and Q mci screen have good to excellent accuracy in a population with movement disorders experiencing cognitive symptoms. The Q mci screen was significantly more accurate for those with early symptoms and had a shorter administration time., Competing Interests: Dr. Rónán O’Caoimh and Prof. D. William Molloy are co-copyright holders of the Quick Mild Cognitive Impairment Screen. The authors report no other conflict of interest., (© 2024 – The authors. Published by IOS Press.)

Background: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement., Methods: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed., Findings: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group., Interpretation: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease., Funding: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation., Competing Interests: Declaration of interests MJF reports speaker's fees from Menarini and Philips. CAR reports consulting fees from Philips and speaker's fees from Menarini. FAS reports speaker's fees and travel support from Servier pharmaceuticals. JRD reports grants from Medtronic and Abbott; sponsorship from Vascular Perspectives, Boston Scientific, Medtronic, and Abbott; and speaker's honoraria from AstraZeneca, Pfizer, Bristol Myers Squibb, and Novartis. TRK reports being on an advisory board for Abbott Vascular and SMT; institutional research funding from Terumo, Medtronic, Boston Scientific, Abbott Vascular, Philips Volcano, and Cardionovum; and travel support from Neovasc. CC reports grant support, honoraria, and travel support from Shockwave and Boston Scientific. JCS reports speaker's fees from Boston Scientific, Shockwave, and Medtronic; and institutional research funding from Boston Scientific and Shockwave. PDO’K reports speaker's fees from Abbott Vascular, Biosensors, Boston Scientific, Philips, Shockwave, and Terumo; and advisory boards for Shockwave Medical, Abbott Vascular, and Philips. RDS reports consulting and advisory fees, institutional research support, and speaking fees for Shockwave; and speaking fees and institutional research support from Abbott Vascular. JMH reports speaker's fees, honoraria, and research support from Abbott Vascular, Abiomed, Boston Scientific, Medtronic, and Shockwave; and equity in Shockwave. SSN reports speaker fees from Philips, Pfizer, Bayer, AstraZeneca, Boehringer Ingelheim, and Amarin; and leadership or board roles in the British Cardiac Intervention Society and the Royal Society of Medicine. SS reports speaker's and consultancy fees from Philips, Medtronic, Recor, and AstraZeneca. RP reports consultant fees from Philips and Abbott. GWM reports honoraria from Medtronic and directorship of the Imperial Valve and Cardiovascular Course. RK reports speaker's fees from Medtronic; and consultancy for Novartis, Amgen, and Cryotherapeutics. TK reports honoraria from Bayer and Jansen and travel support from Jansen. GDC reports shares in Mycardium AI. JPH reports shares in Mycardium AI and grant support from the British Heart Foundation. MJS-S reports consulting fees from Mycardium AI and Medtronic. RKA-L reports being on a trial steering committee for Janssen Pharmaceuticals; being on an advisory board for Abbot and Philips; speaker's honoraria for Abbott, Philips, Medtronic, Servier, Omniprex, and Menarini; and grant support from the British Heart Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosures M.J. Foley, C.A. Rajkumar, and Dr Al-Lamee have received speakers’ honoraria from Philips Volcano and Menarini Pharmaceuticals. Dr Simader has received speaker’s honoraria from Servier Pharmaceuticals. The other authors report no conflicts.

The coronary sinus Reducer (CSR) is an hourglass-shaped device which creates an artificial stenosis in the coronary sinus. Whilst placebo-controlled data show an improvement in angina, these results are unreplicated and are the subject of further confirmatory research. The mechanism of action of this unintuitive therapy is unknown. The Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischaemia, and Microvascular Resistance (ORBITA-COSMIC) trial is a randomised, placebo-controlled, double-blind trial investigating the efficacy of the CSR. Patients with (i) established epicardial coronary artery disease, (ii) angina on maximally tolerated antianginal medication, (iii) evidence of myocardial ischaemia and (iv) no further options for percutaneous coronary intervention or coronary artery bypass grafting will be enrolled. Upon enrolment, angina and quality-of-life questionnaires, treadmill exercise testing and quantitative stress perfusion cardiac magnetic resonance (CMR) imaging will be performed. Participants will record their symptoms daily on a smartphone application throughout the trial. After a 2-week symptom assessment phase, participants will be randomised in the cardiac catheterisation laboratory to CSR or a placebo procedure. After 6 months of blinded follow-up, all prerandomisation tests will be repeated. A prespecified subgroup will undergo invasive coronary physiology assessment at prerandomisation and follow-up. The primary outcome is stress myocardial blood flow on CMR. Secondary outcomes include angina frequency, quality of life and treadmill exercise time. (ClinicalTrials.gov: NCT04892537).

Background: The recent rediscovery of the FLASH effect, a normal tissue sparing phenomenon observed in ultra-high dose rate (UHDR) irradiations, has instigated a surge of research endeavors aiming to close the gap between experimental observation and clinical treatment. However, the dependences of the FLASH effect and its underpinning mechanisms on beam parameters are not well known, and large-scale in vivo studies using murine models of human cancer are needed for these investigations., Purpose: To commission a high-throughput, variable dose rate platform providing uniform electron fields (≥15 cm diameter) at conventional (CONV) and UHDRs for in vivo investigations of the FLASH effect and its dependences on pulsed electron beam parameters., Methods: A murine whole-thoracic lung irradiation (WTLI) platform was constructed using a 1.3 cm thick Cerrobend collimator forming a 15 × 1.6 cm 2 slit. Control of dose and dose rate were realized by adjusting the number of monitor units and couch vertical position, respectively. Achievable doses and dose rates were investigated using Gafchromic EBT-XD film at 1 cm depth in solid water and lung-density phantoms. Percent depth dose (PDD) and dose profiles at CONV and various UHDRs were also measured at depths from 0 to 2 cm. A radiation survey was performed to assess radioactivation of the Cerrobend collimator by the UHDR electron beam in comparison to a precision-machined copper alternative., Results: This platform allows for the simultaneous thoracic irradiation of at least three mice. A linear relationship between dose and number of monitor units at a given UHDR was established to guide the selection of dose, and an inverse-square relationship between dose rate and source distance was established to guide the selection of dose rate between 20 and 120 Gy·s -1 . At depths of 0.5 to 1.5 cm, the depth range relevant to murine lung irradiation, measured PDDs varied within ±1.5%. Similar lateral dose profiles were observed at CONV and UHDRs with the dose penumbrae widening from 0.3 mm at 0 cm depth to 5.1 mm at 2.0 cm. The presence of lung-density plastic slabs had minimal effect on dose distributions as compared to measurements made with only solid water slabs. Instantaneous dose rate measurements of the activated copper collimator were up to two orders of magnitude higher than that of the Cerrobend collimator., Conclusions: A high-throughput, variable dose rate platform has been developed and commissioned for murine WTLI electron FLASH radiotherapy. The wide field of our UHDR-enabled linac allows for the simultaneous WTLI of at least three mice, and for the average dose rate to be modified by changing the source distance, without affecting dose distribution. The platform exhibits uniform, and comparable dose distributions at CONV and UHDRs up to 120 Gy·s -1 , owing to matched and flattened 16 MeV CONV and UHDR electron beams. Considering radioactivation and exposure to staff, Cerrobend collimators are recommended above copper alternatives for electron FLASH research. This platform enables high-throughput animal irradiation, which is preferred for experiments using a large number of animals, which are required to effectively determine UHDR treatment efficacies., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown., Methods: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina., Results: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group., Conclusions: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.)., (Copyright © 2023 Massachusetts Medical Society.)

Unscheduled interruptions to radiotherapy treatments lead to decreased tumor control probability (TCP). Rapid cell repopulation in the tumor increases due to the absence of radiation dose, resulting in the loss of TCP. Compensation for this loss is required to prevent or reduce an extension of the patient's overall treatment time and regain the original TCP. The cyberattack on the Irish public health service in May 2021 prevented radiotherapy treatment delivery resulting in treatment interruptions of up to 12 days. Current standards for treatment gap calculations are performed using the Royal College of Radiologists (RCR) methodology, using a point-dose for planning target volume (PTV) and the organs at risk (OAR). An in-house tool, named EQD 2 VH, was created in Python to perform treatment gap calculations using the dose-volume histogram (DVH) information in DICOM data extracted from commercial treatment planning system plans. The physical dose in each dose bin was converted into equivalent dose in 2-Gy fractions (EQD 2 ), accounting for tumor cell repopulation. This EQD 2 -based DVH provides a 2D representation of the impact of treatment gap compensation strategies on both PTV and OAR dose distributions compared to the intended prescribed treatment plan. This additional information can aid clinicians' choice of compensation options. EQD 2 VH was evaluated using five high-priority patients experiencing a treatment interruption when the cyberattack occurred. Compensation plans were created using the RCR methodology to evaluate EQD 2 VH as a decision-making tool. The EQD 2 VH method demonstrated that the comparison of compensated treatment plans alongside the original intended treatment plans using isoeffective DVH analysis can be achieved. It enabled a visual and quantitative comparison between treatment plan options and provided an individual analysis of each structure in a patient's plan. It demonstrated potential to be a useful decision-making tool for finding a balance between optimizing dose to PTV while protecting OARs., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: The purpose of this study was to compare low-dose-rate prostate brachytherapy treatment plans created using three retrospectively applied planning techniques with plans delivered to patients., Methods and Materials: Treatment plans were created retrospectively on transrectal ultrasound (TRUS) scans for 26 patients. The technique dubbed 4D Brachytherapy was applied, using TRUS and MRI to obtain prostatic measurements required for the associated webBXT online nomogram. Using a patient's MRI scan to create a treatment plan involving loose seeds was also explored. Plans delivered to patients were made using an intraoperative loose seed TRUS-based planning technique. Prostate V 100 (%), prostate V 150 (%), prostate D 90 (Gy), rectum D 0.1cc (Gy), rectum D 2cc (Gy), urethra D 10 (%), urethra D 30 (%), and prostate volumes were measured for each patient. Statistical analysis was used to assess and compare plans., Results: Prostate volumes measured by TRUS and MRI were significantly different. Prostate volumes calculated by the webBXT online nomogram using TRUS- and MRI-based measurements were not significantly different. Compared with delivered plans, TRUS-based 4D Brachytherapy plans showed significantly lower rectum D 0.1cc (Gy) values, MRI-based 4D Brachytherapy plans showed significantly higher prostate V 100 (%) values and significantly lower rectum D 0.1cc (Gy), urethra D 10 (%), and urethra D 30 (%) values, and loose seed MRI-based plans showed significantly lower prostate V 100 (%), prostate D 90 (Gy), rectum D 0.1cc (Gy), rectum D 2cc (Gy), urethra D 10 (%), and urethra D 30 (%) values., Conclusions: TRUS-based 4D Brachytherapy plans showed similar dosimetry to delivered plans; rectal dosimetry was superior. MRI can be integrated into the 4D Brachytherapy workflow. The webBXT online nomogram overestimates the required number of seeds., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Stroke can cause physical and emotional problems affecting sexual well-being; healthcare professionals (HCPs) are often uncomfortable discussing this topic with patients. We explored the perspectives of HCPs and stroke survivors about barriers to discussing sexual well-being poststroke., Design: A mixed methodology was employed., Methods: A postal survey of stroke survivors (n = 50), a focus group with HCPs on a stroke unit (n = 6), and a focus group with community-living stroke survivors (n = 6) were used in this study. Focus group data were analyzed thematically., Findings: No patient surveyed (60% response rate) had discussed sexual well-being with an HCP. Focus groups revealed barriers on multiple levels: structural, HCP, patient, and professional-patient interface., Conclusions: Healthcare professionals were poorly trained, adopted a passive role, and addressed sexual activity based on individual beliefs rather than having an agreed team approach., Clinical Relevance: Relatively simple steps like inclusion in policy, training to empower HCPs, and the provision of written information for patients could help to improve practice.

Current practice when delivering dose for superficial skin radiotherapy is to adjust the monitor units so that the prescribed dose is delivered to the central axis of the superficial unit applicator. Variations of source-to-surface distance due to patient's anatomy protruding into the applicator or extending away from the applicator require adjustments to the monitor units using the inverse square law. Off-axis dose distribution varies significantly from the central axis dose and is not currently being quantified. The dose falloff at the periphery of the field is not symmetrical in the anode-cathode axis due to the heel effect. This study was conducted to quantify the variation of dose across the surface being treated and model a simple geometric shape to estimate a patient's surface with stand-in and stand-off. Isodose plots and color-coded dose distribution maps were produced from scans of GAFChromic EBT-3 film irradiated by a Gulmay D3300 orthovoltage x-ray therapy system. It was clear that larger applicators show a greater dose falloff toward the periphery than smaller applicators. Larger applicators were found to have a lower percentage of points above 90% of central axis dose (SA90). Current clinical practice does not take this field variation into account. Stand-in can result in significant dose falloff off-axis depending on the depth and width of the protrusion, while stand-off can result in a flatter field due to the high-dose region near the central axis being further from the source than the peripheral regions. The central axis also received a 7% increased or decreased dose for stand-in or stand-off, respectively., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objective: The objective of this study was to validate the proof of concept of a computer-simulated cranial distraction, demonstrating accurate shape and end volume., Design: Detailed modeling was performed on pre- and postoperative computed tomographic (CT) scans to generate accurate measurements of intracranial volume. Additionally, digital distraction simulations were performed on the preoperative scan and the resultant intracranial volume and shape were evaluated., Setting: Tertiary Children's Hospital., Patients, Participants: Preoperative and postoperative CT images were used from 10 patients having undergone cranial distraction for cephalocranial disproportion., Interventions: None; computer simulation., Main Outcome Measure: Computer simulation feasibility of cranial vault distraction was demonstrated through creation of digital osteotomies, simulating distraction through translating skull segments, followed by simulated consolidation. Accuracy of the model was evaluated through comparing the intracranial volumes of actual and simulated distracted skulls., Results: The developed digital distraction simulation was performed on the CT images of 10 patients. Plotting the relationship between the actual and simulated postdistraction volumes for the 10 patients yielded a slope of 1.0 and a correlation coefficient of 0.99. The average actual resultant volume change from distraction was 77.0 mL, compared to a simulated volume change of 76.9 mL., Conclusions: Digital simulation of cranial distraction was demonstrated through manipulation of the CT images and confirmed by comparing the actual to simulated volume change. This process may provide objective data in designing an individual distraction plan to optimize volume expansion and resultant cranial shape as well as patient education.

Purpose: The aim of this study was to estimate changes in surface dose due to the presence of the Clarity Autoscan™ ultrasound (US) probe during prostate radiotherapy using Monte Carlo (MC) methods., Methods: MC models of the Autoscan US probe were developed using the BEAMnrc/DOSXYZnrc code based on kV and MV CT images. CT datasets were converted to voxelized mass density phantoms using a CT number-to-mass density calibration. The dosimetric effect of the probe, in the contact region (an 8 mm × 12 mm single layer of voxels), was investigated using a phantom set-up mimicking two scenarios (a) a transperineal imaging configuration (radiation beam perpendicular to the central US axial direction), and (b) a transabdominal imaging configuration (radiation beam parallel to the central US axial direction). For scenario (a), the dosimetric effect was evaluated as a function of the probe to inferior radiation field edge distance. Clinically applicable distances from 5 mm separation to 2 mm overlap were determined from the radiotherapy plans of 27 patients receiving Clarity imaging. Overlaps of 3 to 14 (1 to 3 SD) mm were also considered to include the effect of interfraction motion correction. The influence of voxel size on surface dose estimation was investigated. Approved clinical plans from two prostate patients were used to simulate worst-case dosimetric impact of the probe when large couch translations were applied to correct for interfraction prostate motion., Results: The dosimetric impact of both the MV and kV probe models agreed within ±2% for both beam configurations. For scenario (a) and 1 mm voxel model, the probe gave mean dose increases of 1.2% to 4.6% (of the dose at isocenter) for 5 mm separation to 0 mm overlap in the probe-phantom contact region, respectively. This increased to 27.5% for the largest interfraction motion correction considered (14 mm overlap). For separations of ≥ 2 mm dose differences were < 2%. Simulated dose perturbations were found to be superficial; for the 14 mm overlap the dose increase reduced to < 3% at 5.0 mm within the phantom. For scenario (b), dose increases due to the probe were < 5% in all cases. The dose increase was underestimated by up to ~13% when the voxel size was increased from 1 mm to 3 mm. MC simulated dose to the PTV and OARs for the two clinical plans considered showed good agreement with commercial treatment planning system results (within 2%). Mean dose increases due to the presence of the probe, after the maximum interfraction motion correction, were ~16.3% and ~8.0%, in the contact region, for plan 1 and plan 2, respectively., Conclusions: The presence of the probe results in superficial dose perturbations for patients with an overlap between the probe and the radiation field present in either the original treatment plan or due to translation of the radiation field to simulate correction of interfraction internal prostate motion., (© 2017 American Association of Physicists in Medicine.)

Background: Palliative care is recommended for non-malignant illnesses, including Parkinson's disease. However, past research with healthcare workers highlights unmet palliative needs in this population and referral rates to Specialist Palliative Care are low. Some healthcare workers perceive a 'fear' in their patients about introducing palliative care. However, less is known about the views of people with Parkinson's disease and their carers about palliative care., Aim: (1) To explore the palliative care and related issues most affecting people with Parkinson's disease and their families and (2) to examine perceptions about/understanding of palliative care., Design: This was a qualitative study; semi-structured interviews were conducted, transcribed and analysed using thematic analysis., Setting/participants: A total of 31 people participated, both people with Parkinson's disease ( n = 19) and carers ( n = 12), across three Movement Disorder Clinics in the Republic of Ireland., Results: People with Parkinson's disease and their carers were unfamiliar with the term palliative care. When informed of the role of palliative care, most felt that they would benefit from this input. People with Parkinson's disease and carers experienced a high illness burden and wanted extra support. Crises requiring Specialist Palliative Care involvement may occur at diagnosis and later, with advancing illness. Participants wanted more information about palliative care and especially further supports to address their psychosocial needs., Conclusion: A holistic palliative care approach could address the complex physical and psychosocial symptoms experienced by people with Parkinson's disease and their carers, and people with Parkinson's disease and their carers are open to palliative care. Further research needs to explore how palliative care can be introduced into the routine care for people with Parkinson's disease.

Seven different types of radon detectors (Atmos 12 dpx, RAD7, RStone, Sun Nuclear 1028, Ramon 2.2, Canary and CR-39) were compared for exposure periods of 1, 2, 3 and 4 weeks. The comparison was conducted under two conditions: (a) in a purpose-built radon chamber with an average radon concentration of 2560 Bq m(-3) (b) in a home environment with a radon concentration of 57 Bq m(-3), in both cases measured by the reference detector (Atmos 12 dpx) with a  ±10% uncertainty range. In (a) 5 out of 8 detectors recorded radon concentrations within the Atmos uncertainty range and all detectors recorded within  ±15%; in (b) 3 out of 9 detectors recorded within the Atmos uncertainty range and 6 out of 9 measured within  ±20%, for a 4 week measurement. The results from this study show that radon surveys can be conducted for shorter periods than the recommended 3 months where a rapid indication is needed of whether the radon concentration is above the reference level, such as when assessing the concentration during and after remediation work.

IMRT QA requires, among other tests, a time-consuming process of measuring the absorbed dose, at least to a point, in a high-dose, low-dose-gradient region. Some clinics use a technique of measuring this dose with all beams delivered at a single gantry angle (collapsed delivery), as opposed to the beams delivered at the planned gantry angle (rotated delivery). We examined, established, and optimized Monte Carlo simulations of the dosimetry for IMRT verification of treatment plans for these two different delivery modes (collapsed versus rotated). The results of the simulations were compared to the treatment planning system dose calculations for the two delivery modes, as well as to measurements taken. This was done in order to investigate the validity of the use of a collapsed delivery technique for IMRT QA. The BEAMnrc, DOSXYZnrc, and egs&#95;chamber codes were utilized for the Monte Carlo simulations along with the MMCTP system. A number of different plan complexity metrics were also used in the analysis of the dose distributions in a bid to qualify why verification in a collapsed delivery may or may not be optimal for IMRT QA. Following the Alfonso et al. formalism, the kfclin,frefQclin,Q correction factor was calculated to correct the deviation of small fields from the reference conditions used for beam calibration. We report on the results obtained for a cohort of 20 patients. The plan complexity was investigated for each plan using the complexity metrics of homogeneity index, conformity index, modulation complexity score, and the fraction of beams from a particular plan that intersect the chamber when performing the QA. Rotated QA gives more consistent results than the collapsed QA technique. The kfclin,frefQclin,Qfactor deviates less from 1 for rotated QA than for collapsed QA. If the homogeneity index is less than 0.05 then the kfclin,frefQclin,Q factor does not deviate from unity by more than 1%. A value this low for the homogeneity index can only be obtained with the rotated QA technique.

This work outlines the development of a multi-pinhole SPECT system designed to produce a synthetic-collimator image of a small field of view. The focused multi-pinhole collimator was constructed using rapid-prototyping and casting techniques. The collimator projects the field of view through forty-six pinholes when the detector is adjacent to the collimator. The detector is then moved further from the collimator to increase the magnification of the system. The amount of pinhole-projection overlap increases with the system magnification. There is no rotation in the system; a single tomographic angle is used in each system configuration. The maximum-likelihood expectation-maximization (MLEM) algorithm is implemented on graphics processing units to reconstruct the object in the field of view. Iterative reconstruction algorithms, such as MLEM, require an accurate model of the system response. For each system magnification, a sparsely-sampled system response is measured by translating a point source through a grid encompassing the field of view. The pinhole projections are individually identified and associated with their respective apertures. A 2D elliptical Gaussian model is applied to the pinhole projections on the detector. These coefficients are associated with the object-space location of the point source, and a finely-sampled system matrix is interpolated. Simulations with a hot-rod phantom demonstrate the efficacy of combining low-resolution non-multiplexed data with high-resolution multiplexed data to produce high-resolution reconstructions.

This work outlines the design and construction of a single-photon emission computed tomography imaging system based on the concept of synthetic collimation. A focused multi-pinhole collimator is constructed using rapid-prototyping and casting techniques. The collimator projects the centre of the field of view (FOV) through 46 pinholes when the detector is adjacent to the collimator, with the number reducing towards the edge of the FOV. The detector is then moved further from the collimator to increase the magnification of the system. The object distance remains constant, and each new detector distance is a new system configuration. The level of overlap of the pinhole projections increases as the system magnification increases, but the number of projections subtended by the detector is reduced. There is no rotation in the system; a single tomographic angle is used in each system configuration. Image reconstruction is performed using maximum-likelihood expectation-maximization and an experimentally measured system matrix. The system matrix is measured for each configuration on a coarse grid, using a point source. The pinholes are individually identified and tracked, and a Gaussian fit is made to each projection. The coefficients of these fits are used to interpolate the system matrix. The system is validated experimentally with a hot-rod phantom. The Fourier crosstalk matrix is also measured to provide an estimate of the average spatial resolution along each axis over the entire FOV. The 3D synthetic-collimator image is formed by estimating the activity distribution within the FOV and summing the activities in the voxels along the axis perpendicular to the collimator face.

This paper presents an alternative method to tune Monte Carlo electron beam parameters to match measured data using a minimal set of variables in order to reduce the model setup time prior to clinical implementation of the model. Monte Carlo calculations provide the possibility of a powerful treatment planning verification technique. The nonstandardized and nonautomated process of tuning the required accelerator model is one of the reasons for delays in the clinical implementation of Monte Carlo techniques. This work aims to establish and verify an alternative tuning method that can be carried out in a minimal amount of time, allowing it to be easily implemented in a clinical setting by personnel with minimal experience with Monte Carlo methods. This tuned model can then be incorporated into the MMCTP system to allow the system to be used as a second dose calculation check for IMRT plans. The technique proposed was used to establish the primary electron beam parameters for accelerator models for the Varian Clinac 2100 6 MV photon beam using the BEAMnrc Monte Carlo system. The method is intended to provide a clear, direct, and efficient process for tuning an accelerator model using readily available clinical quality assurance data. The tuning provides a refined model, which agrees with measured dose profile curves within 1.5% outside the penumbra or 3 mm in the penumbra, for square fields with sides of 3 cm up to 30 cm. These models can then be employed as the basis for Monte Carlo recalculations of dose distributions, using the MMCTP system, for clinical treatment plans, providing an invaluable assessment tool. This was tested on six IMRT plans and compared to the measurements performed for the pretreatment QA process. These Monte Carlo values for the average dose to the chamber volume agreed with measurements to within 0.6%.

An extendable x-ray multi-leaf collimator (eMLC) is investigated for collimation of electron beams on a linear accelerator. The conventional method of collimation using an electron applicator is impractical for conformal, modulated and mixed beam therapy techniques. An eMLC would allow faster, more complex treatments with potential for reduction in dose to organs-at-risk and critical structures. The add-on eMLC was modelled using the EGSnrc Monte Carlo code and validated against dose measurements at 6-21 MeV with the eMLC mounted on a Siemens Oncor linear accelerator at 71.6 and 81.6 cm source-to-collimator distances. Measurements and simulations at 8.4-18.4 cm airgaps showed agreement of 2%/2 mm. The eMLC dose profiles and percentage depth dose curves were compared with standard electron applicator parameters. The primary differences were a wider penumbra and up to 4.2% reduction in the build-up dose at 0.5 cm depth, with dose normalized on the central axis. At 90 cm source-to-surface distance (SSD)--relevant to isocentric delivery--the applicator and eMLC penumbrae agreed to 0.3 cm. The eMLC leaves, which were 7 cm thick, contributed up to 6.3% scattered electron dose at the depth of maximum dose for a 10 × 10 cm2 field, with the thick leaves effectively eliminating bremsstrahlung leakage. A Monte Carlo calculated wedge shaped dose distribution generated with all six beam energies matched across the maximum available eMLC field width demonstrated a therapeutic (80% of maximum dose) depth range of 2.1-6.8 cm. Field matching was particularly challenging at lower beam energies (6-12 MeV) due to the wider penumbrae and angular distribution of electron scattering. An eMLC isocentric electron breast boost was planned and compared with the conventional applicator fixed SSD plan, showing similar target coverage and dose to critical structures. The mean dose to the target differed by less than 2%. The low bremsstrahlung dose from the 7 cm thick MLC leaves had the added advantage of reducing the mean dose to the whole heart. Isocentric delivery using an extendable eMLC means that treatment room re-entry and repositioning the patient for SSD set-up is unnecessary. Monte Carlo simulation can accurately calculate the fluence below the eMLC and subsequent patient dose distributions. The eMLC generates similar dose distributions to the standard electron applicator but provides a practical method for more complex electron beam delivery.

Mesenchymal Stem Cells (MSCs) migrate specifically to tumors in vivo, and coupled with their capacity to bypass immune surveillance, are attractive vehicles for tumor-targeted delivery of therapeutic agents. This study aimed to introduce MSC-mediated expression of the sodium iodide symporter (NIS) for imaging and therapy of breast cancer. Tumor bearing animals received an intravenous or intratumoral injection of NIS expressing MSCs (MSC-NIS), followed by (99m) Technetium pertechnetate imaging 3-14 days later using a BazookaSPECT γ-camera. Tissue was harvested for analysis of human NIS (hNIS) expression by relative quantitative-polymerase chain reaction. Therapy animals received an i.p. injection of (131) I or saline 14 days after injection of MSC-NIS, and tumor volume was monitored for 8 weeks. After injection of MSC-NIS, BazookaSPECT imaging revealed an image of animal intestines and chest area at day 3, along with a visible weak tumor image. By day 14, the tumor was visible with a significant reduction in radionuclide accumulation in nontarget tissue observed. hNIS gene expression was detected in the intestines, heart, lungs, and tumors at early time points but later depleted in nontarget tissues and persisted at the tumor site. Based on imaging/biodistribution data, animals received a therapeutic dose of (131) I 14 days after MSC-NIS injection. This resulted in a significant reduction in tumor growth (mean ± SEM, 236 ± 62 mm(3) vs. 665 ± 204 mm(3) in controls). The ability to track MSC migration and transgene expression noninvasively in real time before therapy is a major advantage to this strategy. This promising data supports the feasibility of this approach as a novel therapy for breast cancer., (Copyright © 2011 AlphaMed Press.)

Purpose: Monte Carlo (MC) simulation can be used for accurate electron beam treatment planning and modeling. Measurement of large electron fields, with the applicator removed and secondary collimator wide open, has been shown to provide accurate simulation parameters, including asymmetry in the measured dose, for the full range of clinical field sizes and patient positions. Recently, disassembly of the treatment head of a linear accelerator has been used to refine the simulation of the electron beam, setting tightly measured constraints on source and geometry parameters used in simulation. The simulation did not explicitly include the known deflection of the electron beam by a fringe magnetic field from the bending magnet, which extended into the treatment head. Instead, the secondary scattering foil and monitor chamber were unrealistically laterally offset to account for the beam deflection. This work is focused on accounting for this fringe magnetic field in treatment head simulation., Methods: The magnetic field below the exit window of a Siemens Oncor linear accelerator was measured with a Tesla-meter from 0 to 12 cm from the exit window and 1-3 cm off-axis. Treatment head simulation was performed with the EGSnrc/BEAMnrc code, modified to incorporate the effect of the magnetic field on charged particle transport. Simulations were used to analyze the sensitivity of dose profiles to various sources of asymmetry in the treatment head. This included the lateral spot offset and beam angle at the exit window, the fringe magnetic field and independent lateral offsets of the secondary scattering foil and electron monitor chamber. Simulation parameters were selected within the limits imposed by measurement uncertainties. Calculated dose distributions were then compared with those measured in water., Results: The magnetic field was a maximum at the exit window, increasing from 0.006 T at 6 MeV to 0.020 T at 21 MeV and dropping to approximately 5% of the maximum at the secondary scattering foil. It was up to three times higher in the bending plane, away from the electron gun, and symmetric within measurement uncertainty in the transverse plane. Simulations showed the magnetic field resulted in an offset of the electron beam of 0.80 cm (mean) at the machine isocenter for the exit window only configuration. The fringe field resulted in a 3.5%-7.6% symmetry and 0.25-0.35 cm offset of the clinical beam R(max) profiles. With the magnetic field included in simulations, a single (realistic) position of the secondary scattering foil and monitor chamber was selected. Measured and simulated dose profiles showed agreement to an average of 2.5%/0.16 cm (maximum: 3%/0.2 cm), which is a better match than previously achieved without incorporating the magnetic field in the simulation. The undulations from the 3 stepped layers of the secondary scattering foil, evident in the measured profiles of the higher energy beams, are now aligned with those in the simulated beam. The simulated fringe magnetic field had negligible effect on the central axis depth dose curves and cross-plane dose profiles., Conclusions: The fringe magnetic field is a significant contributor to the electron beam in-plane asymmetry. With the magnetic field included explicitly in the simulation, realistic monitor chamber and secondary scattering foil positions have been achieved, and the calculated fluence and dose distributions are more accurate.

Monte Carlo simulation can accurately calculate electron fluence at the patient surface and the resultant dose deposition if the initial source electron beam and linear accelerator treatment head geometry parameters are well characterized. A recent approach used large electron fields to extract these simulation parameters. This method took advantage of the absence of lower energy, widely scattered electrons from the applicator resulting in more accurate data. It is important to validate these simulation parameters for clinically relevant fields. In the current study, these simulation parameters are applied to fields collimated by applicators and inserts to perform a comprehensive validation. Measurements were performed on a Siemens Oncor linear accelerator for 6 MeV, 9 MeV, 12 MeV, 15 MeV, 18 MeV and 21 MeV electron beams and collimators ranging from an open 25 x 25 cm(2) applicator to a 10 x 10 cm(2) applicator with a 1 cm diameter cerrobend insert. Data were collected for inserts placed in four square applicators. Monte Carlo simulations were performed using EGSnrc/BEAMnrc. Source and geometry parameters were obtained from previous measurements and simulations with the maximum field size (40 x 40 cm(2)). The applicators were modelled using manufacturer specifications, confirmed by direct measurements. Cerrobend inserts were modelled based on calliper measurements. Monte Carlo-calculated percentage depth dose and off-axis profiles agreed with measurements to within the least restrictive of 2%/1 mm in most cases. For the largest applicator (25 x 25 cm(2)), and 18 MeV and 21 MeV beams, differences in dose profiles of 3% were observed. Calculated relative output factors were within 2% of those measured with an electron diode for fields 1.5 cm in diameter or larger. The disagreement for 1 cm diameter fields was up to 5%. For open applicators, simulations agreed with parallel plate chamber-measured relative output factors to 1%. This work has validated a recent methodology used to extract data on the electron source and treatment head from large electron fields, resulting in a reduction in the number of unknown parameters in treatment head simulation. Applicator and insert collimated electron fields were accurately simulated without adjusting these parameters. Results demonstrate that commissioning of electron beams based on large electron field measurements is a viable option.

Electron-beam therapy is used to treat superficial tumors at a standard 100 cm source-to-surface distance (SSD). However, certain clinical situations require the use of an extended SSD. In the present study, Monte Carlo methods were used to investigate clinical electron beams, at standard and non-standard SSDs, from a Siemens Oncor Avant Garde (Siemens Healthcare, Erlangen, Germany) linear accelerator (LINAC). The LINAC treatment head was modeled in BEAMnrc for electron fields 5 cm in diameter and 10 x 10 cm, 15 x 15 cm, and 20 x 20 cm; for 6 MeV, 9 MeV, and 12 MeV; and for 100 cm, 110 cm, and 120 cm SSD. The DOSXYZnrc code was used to calculate extended SSD factors and dose contributions from various parts of the treatment head. The main effects of extended SSD on water phantom dose distributions were verified by Monte Carlo methods. Monte Carlo-calculated and measured extended SSD factors showed an average difference of +/-1.8%. For the field 5 cm in diameter, the relative output at extended SSD declined more rapidly than it did for the larger fields. An investigation of output contributions showed this decline was mainly a result of a rapid loss of scatter dose reaching the d max point from the lower scrapers of the electron applicator. The field 5 cm in diameter showed a reduction in dose contributions; the larger fields generally showed an increased contribution from the scrapers with increase in SSD. Angular distributions of applicator-scattered electrons have shown a large number of acute-angle electron tracks contributing to the output for larger field sizes, explaining the shallow output reduction.

In 1666, Christopher Merrett published "Pinax rerum naturalium britannicarum," this essentially being a catalogue of British plant localities known at the time together with a few other items of natural history. What is thought to be the author's personal annotated copy is held in the British Library. These annotations have been examined and the hand-writing compared to surviving examples known to be either of the author or of one of his sons and are now transcribed. Brief biographical notes relating to Merrett and to the background to his production of the "Pinax" are also given.

To determine if droperidol i.v. is as effective as prochlorperazine i.v. in the emergency department (ED) treatment of uncomplicated headache, a randomized, controlled, blinded study was conducted in the Emergency Departments of two urban teaching hospitals. Patients >or= 18 years old with crescendo-onset headache were eligible for inclusion. Ninety-six patients (48 in each group) were randomized to receive droperidol 2.5 mg i.v. or prochlorperazine 10 mg i.v. Baseline characteristics were similar between the two study groups. For the main study outcome, 83.3% in the droperidol group and 72.3% in the prochlorperazine group reported 50% pain reduction at 30 min (p <.01; one-sided test of equivalence). The mean decrease in headache intensity was 79.1% (SD 28.5%) in the droperidol group and 72.1% (SD 28.0%) in the prochlorperazine group (p =.23). It is concluded that droperidol i.v. provided a similar reduction of headache as achieved with prochlorperazine i.v. with a similar incidence of akathisia.

We present our series of 17 patients who underwent wrist arthrodesis with excision of the proximal row carpal bones using the AO wrist fusion plate and local bone graft obtained from the excised proximal carpal row. All patients were evaluated using a questionnaire to assess pain, function, ability to perform an occupation and satisfaction with the procedure. The mean follow-up was 17 months, at which time all the fusions had united. Clinical outcome scores showed that 14 and 15 of the 17 patients achieved good or excellent results with regard to their current condition and clinical improvement, respectively. Four patients required secondary surgery, two for fractures and two for instability of the distal radio-ulnar joint unrelated to the wrist fusion., (Copyright 2001 The British Society for Surgery of the Hand.)

General base catalysis supplied by the histidine-12 (H-12) residue of ribonuclease (RNase) A has long been appreciated as a major component of the catalytic power of the enzyme. In an attempt to harness the catalytic power of a general base into antibody catalysis of phosphodiester bond hydrolysis, the quaternary ammonium phosphate 1 was used as a bait and switch hapten. Based on precedence, it was rationalized that this positively charged hapten could induce a counter-charged residue in the antibody binding site at a locus suitable for it to deprotonate the 2'-hydroxyl group of the anhydroribitol phosphodiester substrate 2. After murine immunization with hapten 1, mAb production yielded a library of 35 antibodies that bound to a BSA-1 conjugate. From this panel, two were found to catalyze the cyclization-cleavage of phosphodiester 2. Kinetic studies at pH 7.49 (Hepes, 20 mM) and 25 degreesC showed that the most active antibody, MATT.F-1, obeyed classical Michaelis-Menten kinetics with a Km = 104 microM, a kcat = 0.44 min-1, and a kcat/kuncat = 1.7 x 10(3). Hapten 1 stoichiometrically inhibits the catalytic activity of the antibody. MATT.F-1 is the most proficient antibody-catalyst (1.6 x 10(7) M-1) yet generated for the function of phosphodiester hydrolysis and emphasizes the utility of the bait and switch hapten paradigm when generating antibody catalysts for processes for which general-base catalysis can be exploited.

Purpose: The author reports experience with 150 peripheral access system ports (PAS Ports) placed in an interventional radiology suite. Complication rates from this series are compared with those of surgically placed tunneled catheters. The average cost of placement is compared with that of a surgically placed chest port., Patients and Methods: Findings were retrospectively reviewed in 150 patients in whom the PAS Port catheter was implanted. The age range was 26-84 years (mean, 46 years). The diagnoses in these patients included cancer (n = 68), acquired immunodeficiency syndrome (n = 52), osteomyelitis (n = 21), and abscess (n = 9). Implantation with use of fluoroscopic guidance and "Cath-finder" technology is described., Results: One hundred fifty ports have been indwelling for a total of 24,151 patient days (range, 40-220 days; mean duration, 161 days). Sepsis occurred in 3.3%, local infection in 5% (early infection 1%, late infection 4%), temporary catheter occlusion in 3.3%, postinsertion phlebitis in 7.3%, and venous thrombosis in 2%. The cost of radiologic PAS Port insertion averaged $1,488 versus $3,720 for surgical chest port insertion., Conclusion: PAS Port central venous catheter placement by an interventional radiologist in this series is safe and cost effective and compares very favorably with surgery. Radiologists will likely see increasing requests by referring physicians for radiologically placed catheters and ports in this era of cost containment.