Search

Stratospheric aerosol injection is a potential method of climate intervention to reduce climate risk as decarbonization efforts continue. However, possible ecosystem impacts from the strategic design of hypothetical intervention scenarios are poorly understood. Two recent Earth system model simulations depict policy-relevant stratospheric aerosol injection scenarios with similar global temperature targets, but a 10-year delay in intervention deployment. Here we show this delay leads to distinct ecological risk profiles through climate speeds, which describe the rate of movement of thermal conditions. On a planetary scale, climate speeds in the simulation where the intervention maintains temperature are not statistically distinguishable from preindustrial conditions. In contrast, rapid temperature reduction following delayed deployment produces climate speeds over land beyond either a preindustrial baseline or no-intervention climate change with present policy. The area exposed to threshold climate speeds places different scenarios in context to their relative ecological risks. Our results support discussion of tradeoffs and timescales in future scenario design and decision-making. Hueholt et al. find that considering how the rate of temperature change contributes to ecosystem risk helps inform future hypothetical design of climate intervention scenarios [ABSTRACT FROM AUTHOR]

This paper presents the GPDS (Getting Started, Planning, Design, and Sustainability) Planning Framework for Social Marketing. A qualitative research design was employed. Data were collected from social marketing experts using the Delphi method and analyzed using the thematic analysis approach. The proposed framework includes key strengths of existing Social Marketing Planning (SMP) approaches. It also embeds emerging social marketing principles in the planning process, such as 'Continuous Consumer Research and Feedback Loop' (embracing key aspects of monitoring and evaluation) and 'Expert Consultation' to overcome the lack of clarity on the interdisciplinary language used in the field. Importantly, the critical aspect of 'Sustainability' in the changed behavior is incorporated, aligning with the global consensus definition of social marketing and the United Nations' (UN) Sustainable Development Goals (SDGs) focus on sustainable outcomes. Both theory and practice have been applied to the development and verification process of the proposed framework. The framework has consensus from 23 social marketing experts worldwide, drawing on current best practices and experts' opinions/experience in the field. The GPDS Planning Framework for Social Marketing offers a comprehensive list of sources in the accompanying toolkit, including various activities for insight, design, implementation, and evaluation. This enables practitioners to prepare, plan and deliver social marketing programs to sustain behavioral outcomes. This research informs those working in social marketing, social policy, behavioral insight/design, public health, health communication, and service-user experience. These disciplines deploy social marketing practices in the design and delivery of interventions. [ABSTRACT FROM AUTHOR]

The Madden–Julian oscillation (MJO) is a major tropical weather system and one of the largest sources of predictability for subseasonal-to-seasonal weather forecasts. Skillful prediction of the MJO has been a highly active area of research due to its large socio-economic impacts. Silini et al., herein S21, developed a machine learning model to predict the MJO, which they claimed to have an MJO prediction skill of 26–27 days over all seasons and 45 days for December–February (DJF) winter. If true, this would make the skill of their model competitive with that of the state-of-the-art dynamical MJO prediction systems at 20–35 days. However, here we show that the MJO prediction was calculated incorrectly in S21, which spuriously increased the performance of their model. Correctly computed skill of their model was substantially lower than that reported in S21; the skill for all seasons drops to 11–12 days and the skill for forecasts initialized during DJF drops to 15 days. Our findings clarify that the S21 machine learning model is not competitive with state-of-the-art numerical weather prediction models in predicting the MJO. [ABSTRACT FROM AUTHOR]

Purpose: To describe the natural history of autosomal dominant (AD) GUCY2D-associated cone–rod dystrophies (CRDs), and evaluate associated structural and functional biomarkers. Methods: Retrospective analysis was conducted on 16 patients with AD GUCY2D-CRDs across two sites. Assessments included central macular thickness (CMT) and length of disruption to the ellipsoid zone (EZ) via optical coherence tomography (OCT), electroretinography (ERG) parameters, best corrected visual acuity (BCVA), and fundus autofluorescence (FAF). Results: At first visit, with a mean age of 30 years (range 5–70 years), 12 patients had a BCVA below Australian driving standard (LogMAR ≥ 0.3 bilaterally), and 1 patient was legally blind (LogMAR ≥ 1). Longitudinal analysis demonstrated a deterioration of LogMAR by − 0.019 per year (p < 0.001). This accompanied a reduction in CMT of − 1.4 µm per year (p < 0.0001), lengthened EZ disruption by 42 µm per year (p = < 0.0001) and increased area of FAF by 0.05 mm2 per year (p = 0.027). Similarly, cone function decreased with increasing age, as demonstrated by decreasing b-wave amplitude of the light-adapted 30 Hz flicker and fused flicker (p = 0.005 and p = 0.018, respectively). Reduction in CMT and increased EZ disruption on OCT were associated with functional changes including poorer BCVA and decreased cone function on ERG. Conclusion: We have described the natural long-term decline in vision and cone function associated with mutations in GUCY2D and identified a set of functional and structural biomarkers that may be useful as outcome parameters for future therapeutic clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Approximately half of all radiotherapy (RT) is delivered with palliative intent. Clinical research in palliative RT aims to manage symptoms, improve quality of life (QoL), evaluate supportive care, and determine optimal dose-fractionation schedules. Our aim was to describe the prevalence of palliative research at the Canadian Association of Radiation Oncology (CARO) Annual Scientific Meeting (ASM) over time and compare this analysis to previously published work which evaluated the years 1992–2002. Methods: Published abstracts (2003–2021) were independently reviewed by two authors who categorized each as curative-intent; palliative-intent; pertaining to both populations; or neither. Abstracts were considered palliative if they described incurable malignancy and interventions primarily for symptom control or QoL. Type of study, primary, site treated, and symptoms palliated were recorded. Descriptive and summary statistics were calculated including one-way ANOVA test for trend. Results: Three hundred thirty-nine out of 4566 abstracts (7.4%, range 2.4–13.9% per year) were classified as palliative. 7.7% (26/339) described phase I–III trials. The main primary site was the lung (39/339) and the most common metastatic site was the bone (34.2%). QoL, symptom and toxicity outcomes were reported in 31.6% (107/339), 37.8% (128/339) and 17.7% (60/339), respectively. The most common symptom investigated was pain (38/339). The proportion of abstracts classified as curative, palliative or reporting toxicity endpoints demonstrated significant change over time (all p<0.0001). Conclusion: While proportion of palliative themed abstracts has increased with time, there remains a significant gap before equivalence with the prevalence of palliative RT in clinical practice is achieved. [ABSTRACT FROM AUTHOR]

Recent studies suggest that the wintertime North Pacific eddy-driven jet stream will strengthen and extend eastward in response to Arctic sea ice loss. Using output from the Polar Amplification Model Intercomparison Project we examine the mean change of the North Pacific wintertime zonal winds, and use cluster analysis to explore the change in sub-seasonal, wintertime variability in zonal winds between experiments with future Arctic sea ice concentrations relative to a pre-industrial run. Further, given the relationship between the North Pacific jet stream and North American weather regimes, we also examine the changes in surface temperature variability over North America. The four climate models investigated here exhibit robust agreement in both sign and structure of the atmospheric responses, with a strengthened wintertime North Pacific jet, an increase in anomalously strong and extended jet events, and a decreased frequency of weakened and equatorward-shifted jet events in response to reduced Arctic sea ice. The models also show changes in wintertime, North American surface temperature patterns that are consistent with the zonal wind changes seen in the North Pacific. There is an increase in the frequency of occurrence of the North American temperature dipole pattern, defined as anomalously warm temperatures in the west or northwest and anomalously cold temperatures in the east or southeast, and a decrease in the frequency of anomalously cold temperatures over North America. [ABSTRACT FROM AUTHOR]

Background: VAPOUR found vertebroplasty (V) more effective than placebo (P) in patients with severe pain and fracture duration less than 6 weeks. Exploratory analysis suggested that benefits were concentrated in the subgroup of patients with fractures ≤ 3-week duration. This difference may account for the three negative blinded trials that included few patients within this fracture time frame. Purpose: To assess the safety and efficacy of early vertebroplasty for acute painful vertebral osteoporotic fractures within 3 weeks of fracture onset in the VAPOUR study. Methods: Spearman's rank log coefficients were calculated to reassess the relationship of pain reduction from vertebroplasty and fracture duration in the VAPOUR trial. We more fully report baseline and outcome data in patients with fractures ≤ 3-week duration. Results: There were 46V and 47P patients with fractures ≤ 3-week duration. Baseline characteristics were similar. In total, 86 patients (41V, 45P) completed the 14-day questionnaire. The proportion of patients with reduction in pain from severe (NRS ≥ 7/10 was an inclusion requirement) to mild (NRS < 4) at 14 days was 21 (51%) V-group and 9 (20%) in the P-group (between-group difference 31 percentage points, 95% CI 12–50; p = 0.002). Early vertebroplasty provided greater reductions in mean NRS pain and Roland–Morris Disability. Conclusion: Analysis of this patient subgroup from the VAPOUR trial, in the context of other randomised trial evidence, suggests clinically significant benefits from early vertebroplasty if performed within 3 weeks of fracture. These slides can be retrieved from Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

Purpose: Dyspnea is frequently experienced in advanced cancer patients and is associated with poor prognosis and functional decline. This study used the Edmonton Symptom Assessment System (ESAS) to characterize the relationship between dyspnea and concurrent symptoms experienced by advanced cancer patients.Methods: A prospective database was collected and analyzed to extract patient demographics and ESAS scores. Logistic regression analysis and generalized estimating equations (GEE) identified correlations of other ESAS symptoms in three categories: severity of dyspnea (none, mild, moderate, severe), moderate/severe dyspnea (ESAS ≥ 4), and presence of dyspnea (ESAS ≥ 1), at patients' first visit and over time, respectively.Results: Multivariable analysis revealed drowsiness (p = 0.001), and anxiety (p = 0.01) and appetite loss (p = 0.02) were associated with increased severity of dyspnea at first visit. Over time, tiredness (p = 0.02), drowsiness (p = 0.04), nausea (p = 0.02), and anxiety (p = 0.0006) were more likely to experience increased dyspnea severity. Tiredness (p = 0.0003), depression (p = 0.03), and appetite loss (p = 0.003) were significant for moderate/severe dyspnea at first visit. Over multiple visits, tiredness (p < 0.0001), anxiety (p = 0.0008), and appetite loss (p = 0.0008) had higher probabilities of moderate/severe dyspnea. For the presence of dyspnea at the first visit, anxiety (p = 0.03) and drowsiness (p = 0.002) were significantly correlated with an increased frequency of dyspnea. Over time, anxiety (p < 0.0001) and drowsiness (p < 0.0001) remained significant with the addition of nausea (p = 0.0007).Conclusions: The highly interactive relationship between dyspnea and other common cancer symptoms necessitates the development of comprehensive symptom assessments and utilization of multimodal management approaches that consider concurrent symptoms for improved identification and treatment of dyspnea. [ABSTRACT FROM AUTHOR]

Introduction: The Rapid Response Radiotherapy Program (RRRP) is an outpatient radiotherapy clinic for palliative cancer patients where consultation, planning, and radiation treatment can take place in 1 day, allowing for rapid access to care. The objective of this study was to compare the patient population and overall survival of patients seen in the RRRP from 2014 to 2017 to that of patients seen in 1999.Method: Patient characteristics including sex, primary cancer site, sites of metastases, and Karnofsky Performance Status (KPS) were recorded at each clinic visit. Date of death (DOD) was retrieved from the Patient Care System (PCS) and Excelicare. To show overall survival from the first clinic visit, a Kaplan-Meier overall survival curve was generated in all patients from 2014 to 2017.Results: Five hundred ninety-six patients were included in the final analysis. Most patients were male (n = 347) with a primary cancer site of the lung (n = 165) and metastases to the bone (n = 475). Actuarial median overall survival was 15.3 months. In 1999, 395 patients were analyzed, in which a primary of the lung (n = 143) and metastases to the bone (n = 277) were the most prevalent. An additional 72 patients in this population had brain metastases. The actuarial median survival of the 1999 population was 4.5 months.Conclusion: The changing patient population in the RRRP has resulted in visible changes in survival. This may reflect differences in the proportion of patients with specific primaries and sites of metastases, as well as improvements in the availability of palliative radiation over the last two decades. [ABSTRACT FROM AUTHOR]

The aim of this study was an analysis of the changing publication trends over the last three decades in the Journal of Pediatric Surgery (JPS), Pediatric Surgery International (PSI) and European Journal of Pediatric Surgery (EJPS) by studying the bibliometric variables, authorship, collaboration, and citation trends. A previously applied methodology using intermittent years was applied to review the archives of JPS, PSI and EJPS over the last 30 years. Citation data were collected from the Web of Science database. Statistical analysis was performed using SAS 9.4 software. A total of 1917 articles originating from 63 countries met the inclusion criteria. The number of articles published every year increased significantly in the last three decades from 336 in 1987 to 626 in 2017 (P < 0.0001). Multinational papers made up 5% of the total, of which 58% involved more than one continent. A majority of papers (75%) were single institution papers, there was strong evidence of an increase in multi-institution publications over time. There was a statistically significant increase in the number of female first and corresponding author. The publishing landscape of paediatric surgery has evolved to be more inclusive with increased collaboration, female authors and mentors and more publications from developing nations. [ABSTRACT FROM AUTHOR]

Many atmospheric river detection tools (ARDTs) have now been developed. However, their relative performance is not well documented. This paper compares a diverse set of ARDTs by applying them to a single location where a unique 12-year-long time-series from an atmospheric river observatory at Bodega Bay, California is available. The study quantifies the sensitivity of the diagnosed number, duration, and intensity of ARs at this location to the choice of ARDT, and to the choice of reanalysis data set. The ARDTs compared here represent a range of methods that vary in their use of different variables, fixed vs. percentile-based thresholds, geometric shape requirements, Eulerian vs. Lagrangian approaches, and reanalyses. The ARDTs were evaluated first using the datasets documented in their initial publication, which found an average annual count of 19 ± 7. Applying the ARDTs to the same reanalysis dataset yields an average annual count of 19 ± 4. Applying a single ARDT to three reanalyses of varying grid sizes (0.5°, 1.0°–2.5°) showed little sensitivity to the choice of reanalysis. While the annual average AR event count varied by about a factor of two (10–25 per year) depending on the ARDT, average AR duration and maximum intensity varied by less than ± 10%, i.e., 24 ± 2 h duration; 458 ± 44 kg m− 1 s− 1 maximum IVT. ARDTs that use a much higher threshold for integrated vapor transport were compared separately, and yielded just 1–2 ARs annually on average. Generally, ARDTs that include either more stringent geometric criteria or higher thresholds identified the fewest AR events. [ABSTRACT FROM AUTHOR]

Purpose: In brain tumours, brain metastases or advanced cancer; treatment with corticosteroids, side effects can add to symptoms. These are best assessed by patients, complementing clinical assessment. We assessed the feasibility and validity of the Dexamethasone Symptom Questionnaire-Chronic (DSQ-Chronic), patient and caregiver versions.Methods: A longitudinal cohort study was conducted, collecting clinician-rated toxicity, performance status, dexamethasone dose and DSQ-Chronic (patient and caregiver versions) at baseline, then 2, 4 and 8 weeks later. Patients had a primary malignant brain tumour, brain metastases, or advanced cancer; Karnofsky Performance Status ≥40 and predicted survival ≥8 weeks. Analysis included questionnaire completion rates, frequency and severity of dexamethasone-attributable side effects, agreement between patient and caregiver ratings, comparison with clinician-rated toxicity and correlation with performance status.Results: Sixty-six patients were recruited (mean age 60 years), with their caregivers. Completion of questionnaires was over 90% for the dyad at baseline but dropped over time, with caregiver completion rates higher at all timepoints. Agreement between patients and proxies was fair to moderate, and while proxies systematically overestimated symptom severity on DSQ-chronic total scores, the bias was less than 10 points. Patient and clinician agreement was higher for more objective symptoms.Conclusion: The DSQ-Chronic is feasible when the patient is relatively well. As capacity to complete the DSQ-Chronic diminishes, caregivers can be proxy-raters. Clinicians capture corticosteroid toxicities, which may not be obvious to the patient. The DSQ-Chronic, patient and caregiver versions, are useful tools to be used with clinician assessment. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy-induced nausea and vomiting is a common side effect of radiotherapy. It is well-established that nausea and vomiting have a negative impact on quality of life, but the relative influence of each of symptom is infrequently reported. This study aimed to compare the effects of nausea and vomiting on quality of life in cancer patients receiving palliative radiotherapy.Methods: The Functional Living Index-Emesis (FLIE) is a quality of life questionnaire developed in the chemotherapy-induced nausea and vomiting setting. The FLIE consists of 18 questions, half of which address nausea and half of which address vomiting. Three prospective studies on the efficacy of various anti-emetic medications conducted at our center used the FLIE to assess radiotherapy-induced nausea and vomiting at various time points during and after palliative radiotherapy. FLIE data from these three studies were combined for the present analysis. Univariate and multivariate analyses were conducted to assess the relationships between nausea and vomiting, time of FLIE completion, and patient-reported quality of life.Results: Nausea and vomiting scores both decreased patients' quality of life. Multivariate modeling showed that both symptoms significantly influenced patients' ability to enjoy meals. Nausea was also associated with increased hardship for the patient, while vomiting imposed more difficulty on the patients' loved ones.Conclusions: Nausea and vomiting both significantly influence quality of life. Nausea seems to impact the patient more directly, whereas vomiting affects those closest to the patient. [ABSTRACT FROM AUTHOR]

Sean Aas, Dana Howard, and Leslie Francis raise compelling and interesting objections to the definition of disability I defend in The Minority Body. In this paper, I reply to these objections and elaborate on my criticisms of the disability/impairment distinction. [ABSTRACT FROM AUTHOR]

Studies looking at the benefit of surgery at first relapse (second surgery) for recurrent glioblastoma were confounded by including patients with varying grades of glioma, performance status and extent of resection. This case-controlled study aims to remove these confounders to assess the survival impact of second surgery in recurrent glioblastoma. Retrospective data on patients with glioblastoma recurrence at two tertiary Australian hospitals from July 2009 to April 2015 was reviewed. Patients who had surgery at recurrence were matched with those who did not undergo surgery at recurrence, based on the extent of their initial resection and age. Overall survival (OS1 assessed from initial diagnosis and OS2 from the date of recurrence) as well as functional outcomes after resection were analysed. There were 120 patients (60 in each institution); median age at diagnosis was 56 years. Median OS1 was 14 months (95% CI 11.5-15.7) versus 22 months (95% CI 18-25) in patients who did not undergo second surgery and those with surgery at recurrence. OS2 was improved by second surgery (4.7 vs 9.6, HR 0.52, 95% CI 0.38-0.72, P < 0.001), and by chemotherapy, given at recurrence, (HR 0.47, 95% CI 0.24-0.92, P = 0.03). After second surgery, 80% did not require rehabilitation and 61% were independently mobile. Second surgery for recurrent glioblastoma was associated with a survival advantage. Chemotherapy independent of surgery, also improved survival. Functional outcomes were encouraging. More research is required in the era of improved surgical techniques and new antineoplastic therapies. [ABSTRACT FROM AUTHOR]

Competition can have far-reaching consequences for insect fitness and dispersion. Time-lagged interspecific competition is known to negatively affect fitness, yet time-lagged intraspecific competition is rarely studied outside of outbreak conditions. We tested the impact of competition between larval cohorts of the western tent caterpillar (Malacosoma californicum) feeding on chokecherry (Prunus virginiana). We reared larvae on host plants that either had or did not have feeding damage from tent caterpillars the previous season to test the bottom-up fitness effects of intraspecific competition. We measured host-plant quality to test potential mechanisms for bottom-up effects and conducted field oviposition surveys to determine if female adult tent caterpillars avoided host plants with evidence of prior tent caterpillar presence. We found that time-lagged intraspecific competition impacted tent caterpillar fitness by reducing female pupal mass, which is a predictor of lifetime fitness. We found that plants that had been fed upon by tent caterpillars the previous season had leaves that were significantly tougher than plants that had not been fed upon by tent caterpillars, which may explain why female tent caterpillars suffered reduced fitness on these plants. Finally, we found that there were fewer tent caterpillar egg masses on plants that had tent caterpillars earlier in the season than plants without tent caterpillars, which suggests that adult females avoid these plants for oviposition. Our results confirm that intraspecific competition occurs among tent caterpillars and suggests that time-lagged intraspecific competition has been overlooked as an important component of insect fitness. [ABSTRACT FROM AUTHOR]

Purpose: To identify symptom clusters in advanced cancer patients attending a palliative radiotherapy clinic using the Edmonton Symptom Assessment System (ESAS).Methods: Principal component analysis (PCA), exploratory factor analysis (EFA), and hierarchical cluster analysis (HCA) were used to identify symptom clusters among the nine ESAS items using scores from each patient's first visit.Results: ESAS scores from 182 patients were analyzed. The PCA identified three symptom clusters (cluster 1: depression-anxiety-well-being, cluster 2: pain-tiredness-drowsiness, cluster 3: nausea-dyspnea-loss of appetite). The EFA identified two clusters (cluster 1: tiredness-drowsiness-loss of appetite-well-being-pain-nausea-dyspnea, cluster 2: depression-anxiety). The HCA identified three clusters similar to the PCA with an exception of the loss of appetite item being classified under cluster 1 rather than 3. Two to three symptom clusters were identified using three analytical methods, with similar patterns reported in the literature. Particular groups of items co-occurred consistently across all three analyses: depression and anxiety; nausea and dyspnea; as well as pain, tiredness, and drowsiness.Conclusion: Three similar symptom clusters were identified in our patient population using the PCA and HCA; whereas, the EFA produced two clusters: one physical and one psychological cluster. Given the implications of symptom clusters in the management of quality of life, clinicians should be aware of these clusters to aid in the palliative treatment of patients. [ABSTRACT FROM AUTHOR]

Social constructionism is often considered a form of anti-realism. But in contemporary feminist philosophy, an increasing number of philosophers defend views that are well-described as both realist and social constructionist. In this paper, I use the work of Sally Haslanger as an example of realist social constructionism. I argue: (i) that Haslanger is best interpreted as defending metaphysical realism about social structures; (ii) that this type of metaphysical realism about the social world presents challenges to some popular ways of understanding metaphysical realism. [ABSTRACT FROM AUTHOR]

Purpose: Dyspnea is a debilitating symptom commonly experienced by advanced cancer patients that can lead to negative effects on function and quality of life (QOL). The present study aims to determine the relationship between dyspnea and other Edmonton Symptom Assessment System (ESAS) symptoms in palliative cancer patients referred to a radiotherapy clinic.Methods: The presence and severity of dyspnea was measured using the ESAS. All patients that visited a palliative radiotherapy clinic between 1999 to 2002 and 2006 to 2009 and completed the ESAS were included. ESAS scores and other demographic and clinical information were extracted from a prospectively collected database. Statistical tests including chi-squared tests, Spearman correlations, and multivariate analysis were conducted to explore the relationship between dyspnea, other ESAS items, and other demographic factors. Kaplan-Meier overall survival curves were generated based on dyspnea severity.Results: One thousand three hundred forty-four patients were included in the dyspnea analysis; reported moderate or severe dyspnea. Dyspnea severity was significantly associated with eight other ESAS interference severities (p < 0.001). Upon multivariate analysis, greater severity of dyspnea was significantly related to higher ESAS scores for tiredness, nausea, depression, anxious, drowsiness, and poor appetite (p < 0.05). The actuarial median survival time was 6.57 months (95% CI 5.91-7.29 months). There were highly significant differences in overall survival between those with none, mild, and moderate dyspnea (p < 0.0001).Conclusion: Cancer patients often experience dyspnea along with a multitude of other symptoms. Moderate and severe dyspnea should be assessed and optimally managed to reduce functional and QOL debilitations. As presence of increased dyspnea severity is associated with worse overall survival, interventions should occur at the end of life to reduce symptom burden in palliative patients. [ABSTRACT FROM AUTHOR]

In recurrent glioblastoma, health-related quality of life (HRQL) is a crucial trial endpoint. We examined HRQL outcomes as a secondary endpoint for patients in the CABARET randomized phase 2 trial. 122 patients were randomly allocated to bevacizumab monotherapy or bevacizumab plus carboplatin. We calculated change scores from baseline for each HRQL measure on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Brain Cancer Module (QLQ-BN20), together with time to deterioration in HRQL, and the proportion of participants with clinically meaningful improvements in specific disease-related symptoms. At baseline, 117 of 122 randomized patients (96%) attempted questionnaires. Questionnaire participation rates were >90% for patients continuing on treatment, however at the end-of-treatment visit only 72 (64% of eligible participants) returned a form. There were no differences between arms in change scores over the treatment period. Time to ≥10 point deterioration in scores from baseline was also similar between arms. HRQL deterioration occurred largely before progression for the domains tested, but scores in HRQL domains specifically relevant to symptoms of recurrent glioblastoma also improved for about 50% of patients with symptoms at baseline. Neither detrimental nor beneficial effects on HRQL were seen with carboplatin added to bevacizumab, with a proportion of patients on both arms experiencing symptomatic benefit. Given the reduced questionnaire completion at end of treatment, time to HRQL deterioration is a feasible and robust clinical trial endpoint in this patient population. Clinical trials registration number: ACTRN12610000915055. [ABSTRACT FROM AUTHOR]

Purpose: Patients with multiple brain metastases may be treated with whole-brain radiation therapy (WBRT). For these patients, symptom palliation and improvement of quality of life (QOL) and performance status is of the upmost importance. The objective of the present study was to determine the symptom experience and overall QOL in patients with brain metastases before and after WBRT.Methods: A total of 14 symptom scores and overall QOL were collected prospectively in 217 patients for up to 3 months. Wilcoxon signed rank test was applied to determine significant symptoms and QOL changes. Spearman's correlations were applied to determine the relationship between symptom scores and QOL.Results: Appetite loss, weakness, and nausea significantly increased from baseline, while balance, headache, and anxiety significantly decreased from baseline. At baseline, all symptoms other than coordination were significantly correlated with QOL. At 1-month follow-up (FU), changes in concentration, weakness, coordination, and balance were significantly associated with QOL changes. At 2-month FU, changes in pain, insomnia, concentration, balance, and depression were significantly associated with QOL changes. At 3-month FU, only change in nausea was significantly associated with QOL changes.Conclusions: Following WBRT, certain symptoms may influence overall QOL to a greater extent than others, which may fluctuate with time. [ABSTRACT FROM AUTHOR]

In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid Response Radiotherapy Program (RRRP). The objective of this clinic is to consult, simulate, plan, and treat patients with palliative radiotherapy on the same day. In 2004, the RRRP initiated a program to provide clinical and research experience to undergraduate students interested in health sciences. The purpose of this study is to review the 10-year (2004-2013) experience of the RRRP and to examine whether the goals of the student program have been met. Students who worked in the RRRP from 2004 to 2013 were contacted to complete a short survey regarding their overall experience with the program and their current endeavors. Student accomplishments were collected from an internal database as well as PubMed. Descriptive statistics were used to analyze results. A total of 54 students from ten postsecondary institutions have worked in the RRRP; 29 were from the University of Waterloo undergraduate co-op program. In total, 214 articles with first authorship from students were published, 93 (43%) of which can be found on PubMed. Other accomplishments include 40 book chapters, 58 invited presentations, and 99 awards cumulatively. Qualitative data regarding student perspectives of their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP has achieved its goal of providing quality medical and research experience to students interested in the health sciences. Using the responses of past and present students, we hope to continue to shape our program and provide unique opportunities to future students. [ABSTRACT FROM AUTHOR]

Background: Studies utilizing body mass index (BMI) have failed to show a consistent relationship between obesity and survival following treatment for colorectal cancer (CRC). Computerized tomography (CT) offers a reliable alternative approach to quantify body adiposity. We hypothesized that visceral obesity may negatively impact survival in CRC patients. Aims and Methods: A retrospective review of CRC patients who received adjuvant chemotherapy at a single center during the period 2006-2009 identified from a prospectively maintained database. Visceral adiposity was determined by measuring visceral fat area (VFA) on preoperative staging CT. All patients were followed up to study completion or death. Results: Sixty-two CRC patients with a mean age of 63.2 years received adjuvant chemotherapy and had imaging available for analysis. Thirty-five patients (56.5 %) had node positive disease. Thirty-one patients (50 %) were classified viscerally obese based on staging CT. 85.4 % of the patients completed adjuvant chemotherapy and visceral obesity was not associated with increased toxicity or failure to complete treatment. After a median follow-up of 65.2 months, patients with visceral obesity had a significantly lower overall survival (OS) (54.8 % vs 87.1 %, p = 0.004) and disease-free survival (DFS) (48.4 vs 77.4 %, p = 0.007) compared with patients without visceral obesity. There was no relationship between BMI and survival. Multivariate analysis using Cox proportional hazards model showed that visceral obesity was independently associated with reduced OS (Hazard ratio = 7.0; 95 % CI 2.0-24.6; p = 0.002). Conclusion: This study shows that visceral obesity increases the likelihood of a poor prognosis in CRC patients receiving adjuvant chemotherapy thus underlying the value of lifestyle interventions to minimize visceral obesity in this patient cohort. [ABSTRACT FROM AUTHOR]

Emotional processing (EP) from the emotional approach coping measure has been shown to moderate the effect of writing interventions. This study targeted writing interventions to EP level, with low EP participants receiving a best possible self (BPS) script and high EP participants receiving an emotional expression (EMO) script, versus a control (CTL) writing script. A factorial experimental design was used to balance the potential factors gender, spacing of interventions, and whether participants were instructed to keep or give their writing samples to the administrator. Post-test measures were taken 1 month after completion of writing. Sixty-four undergraduates (66 % female) participated. Those with high EP ( $$\hbox {EP}\,\ge \,3$$ ) were assigned EMO or CTL; those with low EP ( $$\hbox {EP}\,\le \,3$$ ) were assigned BPS or CTL. These targeted interventions had significantly better results than CTL for change in last month's need based healthcare visits ( $$p = .0058$$ ) and health symptoms ( $$p = .0107$$ ). Analysis of health symptoms showed that only cold/flu ( $$p = .0369$$ ), headaches ( $$p = .0393$$ ), sinus ( $$p = .0411$$ ), and diarrhea ( $$p = .0089$$ ) showed a significant change. Data modeling suggests that gender, EP, intervention, and spacing were active factors contributing to change in health, and that interactions between them should also be taken into account. Analysis of the CTL intervention showed a marked worsening of health for low EP participants but a mild or negligible effect on health for high EP. [ABSTRACT FROM AUTHOR]

Purpose: Whole brain radiotherapy (WBRT) is a treatment strategy used commonly to relieve burdensome symptoms and improve quality of life (QOL) in patients with multiple brain metastases. The purpose of this study is to determine changes in fatigue score following WBRT as it is a common symptom experienced in this population. Methods: Fatigue and overall QOL scores were collected prospectively in patients for up to 3 months post-WBRT by several questionnaires at different times including the following: Edmonton Symptom Assessment System (ESAS), Brain Symptom and Impact Questionnaire (BASIQ), Spitzer Questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC brain module (EORTC QLQ-BN20 + 2), EORTC QLQ-C15-PAL, and Functional Assessment of Cancer Therapy-General (FACT-G). Questionnaires were grouped for analysis by Wilcoxon Signed Rank test according to the scale of ranking into 0-10, 1-4, and 0-4. Results: Thirty-six patients were interviewed with the ESAS or BASIQ. The median age was 65 years old, and median Karnofsky Performance Status (KPS) was 70. There was a significant increase in fatigue score from baseline to month 1 ( p = 0.02), and months 2 and 3 had no significant change. There was a significant correlation between fatigue and overall QOL score at baseline and month 1 ( p = 0.01, p < 0.0001), respectively. Two hundred and twenty-eight patients were surveyed with Spitzer, C15-PAL, BN20 + 2, QLQ-C30, or FACT-G. Median age was 64 years old and median KPS was 80. Compared to baseline, fatigue score was significantly higher at month 1 ( p < 0.0001) and month 2 ( p = 0.001), with no significant change at month 3. Significant correlation was found between fatigue and overall QOL at baseline, months 1, 2 ( p < 0.0001), and 3 ( p = 0.0009). For all groups, there was no significant change in fatigue score between patients with or without dexamethasone (Dx), except for the fatigue changed score of the group with scale 0-4. Conclusions: Fatigue was significantly increased from baseline to month 1 in all patients, and most patients experienced no difference in fatigue if they were receiving Dx. Increased fatigue was significantly related with decreased overall QOL. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to test the reliability, psychometric, and clinical validity of the use of the Functional Assessment of Cancer Therapy--Brain (FACT-Br) in patients with brain metastases.Methods: Patients with brain metastases were interviewed using the FACT-Br (including the FACT-general) 1 week prior to treatment. All patients completed a follow-up assessment 1 month post-treatment. Patients with a good performance status and receiving stereotactic radiosurgery completed an additional 1 week follow-up assessment after the initial baseline interview to assess test-retest reliability.Results: Forty patients had complete 1 month follow-up data. Ten of these patients also completed the 1 week follow-up assessment from baseline. The median Karnofsky performance status of patients was 80 and the median age was 64 years. All subscales of the FACT-Br were found to be conceptually related (except for two correlations) using the following subscales: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), FACT-G total score, brain cancer subscale (BrC), and the FACT-Br total score. All FACT-Br scores demonstrated excellent reliability, except for the SWB scale which revealed good reliability. The FACT-Br scores showed no significant change in the quality of life (QoL) of patients from baseline to 1 month follow-up.Conclusion: The use of the combined FACT-G and FACT-Br Subscale to assess QoL specifically in patients with brain metastases has successfully undergone psychometric validation. Future clinical trials should use the FACT-G and FACT-Br Subscale to assess QoL in this patient population. [ABSTRACT FROM AUTHOR]

Sider (Four-dimensionalism 2001 ; Philos Stud 114:135–146, 2003 ; Nous 43:557–567, 2009 ) has developed an influential argument against indeterminacy in existence. In what follows, I argue that the defender of metaphysical forms of indeterminate existence has a unique way of responding to Sider’s argument. The response I’ll offer is interesting not only for its applicability to Sider’s argument, but also for its broader implications; responding to Sider helps to show both how we should think about precisification in the context of metaphysical indeterminacy and how we should understand commitment to metaphysically indeterminate existence. And if I’m right that metaphysical indeterminacy can allow for indeterminate existence in a way that semantic indeterminacy can’t, indeterminate existence might actually give us a reason to accept metaphysical indeterminacy (rather than a reason to reject it, as is commonly assumed). [ABSTRACT FROM AUTHOR]

A systematic analysis of the winter North Atlantic eddy-driven jet stream latitude and wind speed from 52 model integrations, taken from the coupled model intercomparison project phase 3, is carried out and compared to results obtained from the ERA-40 reanalyses. We consider here a control simulation, twentieth century simulation, and two time periods (2046-2065 and 2081-2100) from a twenty-first century, high-emission A2 forced simulation. The jet wind speed seasonality is found to be similar between the twentieth century simulations and the ERA-40 reanalyses and also between the control and forced simulations although nearly half of the models overestimate the amplitude of the seasonal cycle. A systematic equatorward bias of the models jet latitude seasonality, by up to 7°, is observed, and models additionally overestimate the seasonal cycle of jet latitude about the mean, with the majority of the models showing equatorward and poleward biases during the cold and warm seasons respectively. A main finding of this work is that no GCM under any forcing scenario considered here is able to simulate the trimodal behaviour of the observed jet latitude distribution. The models suffer from serious problems in the structure of jet variability, rather than just quantitiative errors in the statistical moments. [ABSTRACT FROM AUTHOR]

Purpose: The brief pain inventory (BPI) is often used to assess pain and functional interference as a result of pain in cancer patients. Minor improvements or deteriorations in BPI may be statistically significant due to large sample sizes but may not necessarily be clinically relevant. The purpose of this study was to determine the minimal clinically important differences (MCID) in the functional BPI in patients with pain due to bone metastases. Methods: BPI scores were collected from patients with painful bone metastases who visited the Rapid Response Radiotherapy Program for palliative radiotherapy. Pain and functional interferences scores were also collected monthly for three months. Patients were categorized into 'complete or partial response,' 'pain progression,' and 'indeterminate response' based on their pain scores as recommended by the latest consensus definitions. Anchor-based determination of MCIDs of functional interference scores was calculated by determining the difference between the mean follow-up scores and the mean baseline scores for patients from each of the three response groups. Distribution-based estimates were obtained utilizing 0.2, 0.3, and 0.5 standard deviation (SD) effect sizes and the standard error of measurement. The anchor-based method results were compared with the distribution-based method results. Results: Statistically significant MCIDs were determined for all of the functional interference items of BPI for patients with 'complete or partial response'; whereas, no statistically significant MCIDs in BPI scores could be determined for patients with 'pain progression.' Some of the functional interference items of BPI had statistically significant MCIDs for patients with 'indeterminate response,' although these were generally smaller than patients with complete or partial response. Using the distribution-based approach, an effect size of 0.5 SD was the closest estimate for determining the MCID for both patients with complete or partial response and those with indeterminate response. Conclusions: The MCIDs determined for pain improvement were rather large, where as statistically significant MCIDs could not be detected for pain deterioration. Knowledge of MCIDs utilizing the BPI will allow physicians to evaluate the impact of treatment (or no treatment) on a patient's functional abilities. Knowledge of MCIDs may allow for sample size determination in future clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were to determine whether symptom clusters in patients with bone metastases varied when derived using three different statistical methods and to compare the presentation of symptom clusters over time in responders and nonresponders to palliative radiation treatment (RT). Methods: Secondary analysis of a previously reported data set compiled using the brief pain inventory from 348 patients with bone metastases. Hierarchical cluster analysis (HCA) and exploratory factor analysis (EFA) were performed to identify symptom clusters at baseline, 1, 2, and 3 months following radiation treatment. Clusters derived were compared with the findings obtained using principal component analysis (PCA) in our previous study. The total patient sample was further separated into two subgroups: responders and nonresponders to RT. PCA, HCA, and EFA identified symptom clusters experienced by each subgroup at the same time points as before. Results: Little correlation was observed in the symptom cluster findings of PCA, EFA, and HCA in the total patient sample. Absolute consensus among all three statistical methods was never reached at any assessment time point in the present study. Varying patterns of symptom cluster presentation over time were observed in the responders versus nonresponders subgroups regardless of the analytical method employed. A core cluster of symptoms composed of worst pain, general activity, walking ability, normal work, and enjoyment of life frequently presented in the same cluster. Conclusion: The presence and composition of symptom clusters derived varied depending on which statistical analysis method was employed. A key step in attaining consistency in symptom cluster research necessitates the utilization of a common method. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to compare self-reported quality of life (QOL) scores in old and young patients with metastatic cancer using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire. Materials and methods: Patients receiving palliative radiotherapy (RT) for bone metastases and brain metastases completed the QLQ-C15-PAL questionnaire prior to treatment. Using multiple linear regression analysis, a parametric test, the QLQ-C15-PAL scores were compared using 65 and 70 years as cutoff ages. Results: A total of 340 patients were referred for palliative RT for bone metastases ( n = 190) or brain metastases ( n = 150). Physical functioning and appetite were worse in the older group using either 65 or 70 years as the cutoff age. Age-related differences in the QLQ-C15-PAL scores varied as a function of age cutoff used and location of metastatic site irradiated. Conclusion: Based on the (EORTC) QLQ-C15-PAL, elderly advanced cancer patients have a different QOL profile. Similar observations have been reported with the (EORTC) QLQ-C30 questionnaire. [ABSTRACT FROM AUTHOR]

Purpose: To document the incidence and timing of radiotherapy-induced nausea and vomiting (RINV) in the treatment of bone metastases among patients receiving prophylaxis with a 5-HT receptor antagonist. Methods: Patients receiving single (SF) or multiple fraction (MF) palliative radiotherapy (RT) of moderate or low emetogenic risk for bone metastases were prescribed prophylactic Ondansetron. The frequency and duration of prophylaxis and the use of rescue antiemetics were left to the discretion of the treating physicians. Patients documented episodes of nausea (N) and vomiting (V) in daily diaries before and during RT, and until 10 days following RT completion. Rates of complete prophylaxis (CP) for N&V, respectively (CP = no event and no rescue medication), were calculated for the acute phase (the period from the start of RT to the first day following RT completion inclusive) and the delayed phase (the second to tenth days following RT completion inclusive). Results: Fifty-nine patients were enrolled, and 32 were evaluable. CP rates were as follows: moderate-risk SF group ( n = 16), acute phase (CP for N = 56%, CP for V = 69%) and delayed phase (CP for N = 31%, CP for V = 44%); moderate-risk MF group ( n = 7), acute phase (CP for N = 71%, CP for V = 57%) and delayed phase (CP for N = 43%, CP for V = 57%); low-risk SF group ( n = 8), acute phase (CP for N = 50%, CP for V = 100%) and delayed phase (CP for N = 43%, CP for V = 57%); and low-risk MF group ( n = 1), acute phase (CP for N = 100%, CP for V = 100%) and delayed phase (CP for N = 100%, CP for V = 100%). Conclusions: Despite prophylaxis, RINV was common among patients receiving palliative radiotherapy for bone metastases, especially during the delayed phase. [ABSTRACT FROM AUTHOR]

There is urgent need for a consistent blocking identification method that can be used and compared across reanalyses, models and climate scenarios. We present such a method and diagnose daily blocking frequency in 43 years (1958-2000) of ERA-40 Reanalysis for indices defined on both the commonly used geopotential height and potential temperature fields as well as a zonal wind index. Applications of various blocking indices to the same data highlights the importance of a consistent methodology for comparison and a method that identifies blocks along a path that varies with the latitude of the storm track. Since the method accommodates blocking detection using 500 mb zonal-wind which is readily available in climate model output, we diagnose blocking in 14 CMIP3 models under two different greenhouse gas scenarios. Blocking duration remains nearly constant among the scenarios, but a robust reduction in blocking frequency with global warming is demonstrated. [ABSTRACT FROM AUTHOR]

Introduction: Advanced cancer patients present with a variety of physical and psychological symptoms. Fatigue is one such symptom which reduces overall quality of life and is difficult to manage. The purpose of this study was to report the presence, severity, and correlating factors of fatigue in advanced cancer patients attending an outpatient palliative radiotherapy clinic. Materials/methods: Patients referred to the Rapid Response Radiotherapy Program between January 1999 and October 2009 completed the Edmonton Symptom Assessment System (ESAS) prior to consultation. Demographic information including age, Karnofsky Performance Status (KPS), gender, and primary cancer sites were collected. Ordinal logistic regression analysis was conducted to determine relationships between demographic information, other ESAS items, and levels of fatigue. Multivariate ordinal logistic regression analysis was used to determine the most significant predictors of fatigue. A p value of <0.05 was considered statistically significant. Results: A total of 1,397 patients completed the ESAS prior to consultation. Median age was 68 years (range, 21-95), median KPS was 60 (range, 10-100), and slightly more males completed the ESAS (53.0%). Common primary cancers were of the lung (35.8%), breast (20.7%), and prostate (17.7%). Only 179 (12.8%) patients reported no fatigue; the majority of patients reported moderate (31.8%) or severe (34.4%) fatigue. A low KPS ( p < 0.0001), being female ( p = 0.0056), or being referred for bone metastases ( p = 0.0185) significantly correlated with higher levels of fatigue. Patients with a genitourinary primary cancer ( p = 0.0078) and/or referred for malignant spinal cord compression ( p = 0.0004) reported less fatigue. All other ESAS items were significantly related to fatigue. The most significant predictors of fatigue were pain ( p < 0.0001, odds ratio (OR) = 1.07), nausea ( p = 0.0010, OR = 1.10), depression ( p < 0.0001, OR = 1.10), drowsiness ( p < 0.0001, OR = 1.33), dyspnea ( p = 0.0003, OR = 1.08), and overall well-being ( p < 0.0001, OR = 1.19). Conclusion: Moderate fatigue was reported in over 66% of our advanced cancer patients prior to radiotherapy. Since radiotherapy inherently causes fatigue, proactive and multidisciplinary management is required for these patients. Similar rates of fatigue severity, in lengthier, fatigue-specific tools, suggest that the ESAS may be a good tool for screening the advanced cancer population. [ABSTRACT FROM AUTHOR]

Purpose: Symptom control and improved quality of life (QOL) are primary goals of treatment in palliative oncology. The present study assessed and compared patient demographics, baseline Karnofsky Performance Status (KPS) and QOL using the QLQ-C15-PAL questionnaire prior to palliative radiotherapy (RT) for bone, brain, or lung disease. Few studies have used this questionnaire, an abbreviated version that was developed by the European Organization for Research and Treatment of Cancer specifically for patients with advanced cancer to decrease the burden of completing the longer, more time-consuming QLQ-C30. Methods: Patients referred to an outpatient palliative RT clinic completed QLQ-C15-PAL questionnaires prior to palliative RT for bone, brain, or lung cancer sites. The associations between baseline QLQ-C15-PAL functional/symptom scales, patient demographics, and clinical variables including KPS were explored. Results: When data from all 369 patients were analyzed, higher KPS scores correlated significantly with better overall QOL and higher physical and emotional functioning. The QLQ-C15-PAL provided more detailed information regarding how symptom burden varied depending on disease site. Patients with bone metastases had worse QLQ-C15-PAL scores for pain, while those with brain and lung disease had worse scores for fatigue. Other health-related QOL scores measured by the QLQ-C15-PAL varied as a function of age and gender. Conclusion: As the QLQ-C15-PAL provides detailed and often critical information regarding symptom burden, it may eventually be recognized as a universal core questionnaire to assess QOL in this patient population with advanced cancer while relieving the survey burden. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective of this study was to compare the symptom severity in two different patient populations assessed in an outpatient palliative radiotherapy clinic over two time periods spanning 10 years. The secondary objective was to assess any changes in the baseline demographics of these patients. Methods: Data were collected from 1999 to 2009. Upon initial presentation to the clinic, the Edmonton Symptom Assessment Scale (ESAS) was administered to patients to capture symptom severity. This validated assessment tool asks patients to score their level of pain, tiredness, nausea, depression, anxiety, drowsiness, loss of appetite, well-being, and dyspnea on an 11-point Likert scale. Differences between the two patient groups were assessed using chi-squared analysis and Wilcoxon rank-sum tests. A p value of <0.05 was considered significant. Results: A total of 1,439 patients completed the ESAS from 1999 to 2009. Patients were divided into two time periods 1999-2002 ( n = 689) and 2006-2009 ( n = 750). Pain, depression, nausea, fatigue, anxiety, drowsiness, and dyspnea were significantly better in 2006-2009 ( p < 0.0001). Loss of appetite was not statistically different between the two time periods ( p = 0.236). Significantly more patients with genitourinary cancers ( p = 0.03) or a referral for a mass ( p < 0.0001) were seen in 2006-2009. More patients with breast cancer ( p = 0.04) and bone pain ( p = 0.0002) were seen in 1999-2002. The median age was significantly higher (70 years vs. 68 years, p = 0.03) for patients seen in 2006-2009. No significant differences were seen in performance status or gender between the two groups. Conclusion: There have been statistically significant lower scores in the severity of the majority of symptoms as scored by the latter patient cohort; however, whether this difference in magnitude is clinically significant is debatable. The reason for referral and demographics in patients sent for palliative radiotherapy has changed over a 10-year period. This may be a reflection of the changes in systemic therapies and improvements in supportive care for patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare functional interference and pain response outcomes using the Brief Pain Inventory (BPI) for patients treated with palliative radiotherapy to spine versus non-spine bones and determine if dose fractionation was associated with each group's respective response. Materials and methods: Patients treated for painful bone metastases with palliative radiotherapy during May 2003 to June 2007 were analyzed. The BPI was utilized at baseline and monthly for 6 months post-radiation. Pain response was determined using International Bone Metastases Consensus response definitions. Wilcoxon rank-sum test (for continuous variable), Fisher exact test (for categorical value), and two-way analysis of variance were used for comparisons, and a p value of ≤0.05 was considered statistically significant. Results: Three hundred eighty-six patients were analyzed, 62% were treated with a single fraction, 38% with multiple fractions. Pain and functional interference scores significantly improved over time in both spine and non-spine sites. At 3 months, 42% of all patients had a partial response, and 25% had a complete response. Location of bone metastases and radiotherapy dose were not predictive factors for pain response nor functional interference following radiation treatment. Conclusion: Spine and non-spine bone metastases exhibited similar pain and functional interference improvements over a period of 6 months post-radiotherapy. There were, however, high attrition rates as expected with palliative studies, with approximately half the patients remaining in this study by 3 months and a fifth by 6 months. A single 8 Gy resulted in equal benefits in terms of both pain response and improvement in function. [ABSTRACT FROM AUTHOR]

Purpose: Advanced cancer patients can experience many concurrent symptoms. It has been suggested that certain symptoms can cluster together and have a synergistic effect on patient morbidity. The objective of this study was to explore the presence of symptom clusters in patients with brain metastases treated with whole brain radiotherapy (WBRT).Materials and Methods: Patients with brain metastases were asked to rate their symptoms and quality of life (QOL) using the Spitzer Quality of Life Index (SQLI) and a study-designed 17-item symptom questionnaire. Utilizing a principal component analysis, the SQLI and symptoms were analyzed for the presence of symptom clusters. The Cronbach's alpha statistic was used to estimate the internal consistency and reliability of the derived clusters. Follow-up was carried out at baseline and 1, 2 and 3 months following WBRT.Results: Between August 2005 to October 2007, 129 patients with brain metastases were enrolled. Analysis of the SQLI items revealed two clusters. Cluster 1 consisted of activity, daily living and health, while cluster 2 consisted of support and outlook. Cronbach's alpha was 0.69 and 0.40, respectively, for the two clusters, which accounted for 64% of the total variance. Analysis of the 17 additional symptoms revealed three clusters at baseline. These clusters changed slightly over time, but certain symptoms appeared to remain together: (1) trouble concentrating and confusion, (2) memory loss and decreased alertness, (3) nausea and vomiting, (4) numbness and weakness, and (5) dizziness and headache. These clusters persisted despite WBRT.Conclusion: Symptom clusters exist in patients with brain metastases. Although the clusters varied over time, they did not weaken or disintegrate following WBRT, suggesting the latter one may not significantly improve the QOL and symptom distress in this group. [ABSTRACT FROM AUTHOR]

In this paper we aim to disentangle the thesis that the future is open from theses that often get associated or even conflated with it. In particular, we argue that the open future thesis is compatible with both the unrestricted principle of bivalence and determinism with respect to the laws of nature. We also argue that whether or not the future (and indeed the past) is open has no consequences as to the existence of (past and) future ontology. [ABSTRACT FROM AUTHOR]

Purpose: To update the clinical activity of the Rapid Response Radiotherapy Program (RRRP).Materials and Methods: We conducted a retrospective review of our clinic database from January 2004 until July 2008. The number of patients referred to the RRRP, relevant demographic data, diagnosis and treatment dispositions were recorded. Time interval between referral to consultation and consultation to simulation were also calculated.Results: During the study period, 3,267 patients were seen in the RRRP. Forty-five percent (1,494) of the patients were new to the clinic. Of the 3,267 patients seen, 1,548 (47.4%) were female and 1,719 (52.6%) were male. The median age was 69.2 years (range, 22-101 years). The most common primary sites were lung (34.2%), breast (21.2%) and prostate (17.0%). The majority of patients were referred for palliative treatment of bone metastases (52.4%) or treatment for brain metastases (20.7%). Of the patients referred, 2,311 (70.5%) patients received palliative radiotherapy. The median duration from referral to consultation was 4 days. The majority (82.3%) of patients were simulated and treated within the first 7 days following consultation.Conclusion: The number of patients referred to the RRRP from January 2004-July 2008 remains comparable to our previous report (1996-2003). The overall median interval from referral to consultation for the analysed time period was 4 days. Therefore, we are continuing to meet our goal of providing rapid access to palliative radiation treatment for symptomatic cancer patients. Further information relating to progression and advancements within the clinic aimed at improving our patients' quality of life are explored. [ABSTRACT FROM AUTHOR]

Introduction: The Palliative Performance Scale (PPS) was developed by the Victoria Hospice Society in 1996 to modernize the Karnofsky Performance Scale. Currently, it is being used to measure palliative patient performance status in a variety of settings. Despite its widespread use, only one study has examined the inter-rater reliability of the PPS.Purpose: To examine the inter-rater reliability of the PPS in measuring performance status in patients seen in an outpatient palliative radiation oncology clinicMethods: Performance status for 102 consecutive patients was assessed by an oncologist (MD), a radiation therapist (RT), and a research assistant (RA) in the Rapid Response Radiotherapy Program at the Odette Cancer Centre in Toronto, Ontario, Canada. Raters' scores were analyzed for correlation and compared to evaluate the inter-rater reliability of the PPS tool.Results: Excellent correlation was found between the scores rated by the MD and RA (r = 0.86); good correlation was observed between scores rated by the MD and RT (r = 0.69) and the RT and RA (r = 0.77). Scores between all three raters, as well as between rater pairs, were also found to have good reliability as measured by the Chronbach's alpha coefficient. Significant results were obtained for the range of PPS scores in which the majority of our patients fell: 40-80%.Conclusion: PPS was shown to have good overall inter-rater reliability in an outpatient palliative setting, but more research is needed to establish the validity and reliability of the tool in a variety of different palliative settings. [ABSTRACT FROM AUTHOR]

In this paper I argue that Gareth Evans’ famous proof of the impossibility of de re indeterminate identity fails on a counterpart-theoretic interpretation of the determinacy operators. I attempt to motivate a counterpart-theoretic reading of the determinacy operators and then show that, understood counterpart-theoretically, Evans’ argument is straightforwardly invalid. [ABSTRACT FROM AUTHOR]

Mutations in the transmembrane receptor patched1 (ptc1) are responsible for the majority of basal cell carcinoma (BCC) cases. Many of these mutations, including ptc1-Q688X, result in premature truncation of the ptc1 protein. ptc1-Q688X has been identified in patients with both BCC and nevoid basal cell carcinoma syndrome, an inheritable disorder causing a predisposition to cancer susceptibility. Here we describe a mechanism by which ptc1-Q688X causes constitutive cellular signaling. Cells expressing ptc1-Q688X demonstrate an increase in cell cycle progression and induce cell transformation. The ptc1-Q688X mutant enhances Gli1 activity, a downstream reporter of sonic hedgehog (shh)-ptc1 signaling, independent of shh stimulation. In contrast to wild-type ptc1, ptc1-Q688X fails to associate with endogenous cyclin B1. Expression of nuclear-targeted cyclin B1 derivatives promotes Gli1-dependent transcription, which correlates temporally with cyclin B1-cdk1 kinase activity. Coexpression of wild-type ptc1 with a nuclear-targeted cyclin B1 derivative, mutated to mimic constitutive phosphorylation, dramatically decreases Gli1 activity. In addition, the coexpression of this constitutively nuclear cyclin B1 derivative with ptc1-Q688X substantially enhances foci formation. These studies therefore describe a molecular mechanism for the aberrant activity of ptc1-Q688X that includes the premature activation of the transcription factor Gli1.Oncogene (2005) 24, 902-915. doi:10.1038/sj.onc.1208240 Published online 13 December 2004 [ABSTRACT FROM AUTHOR]

Cell cultures of the continuous human neuroblastoma lines SK-N-SH, SK-N-BE(2), and SK-N-MC at exponential and stationary growth phase have been examined by electron microscopy. At the level of fine structure these cells did not show typical neuronal differentiation such as extensive granular endoplasmic reticulum or neurites with microtubules and neurofilaments. Instead they were characterized by abundant free ribosomes, moderate Golgi complexes, and usually scant granular endoplasmic reticulum, features similar to the fine structure of early normal embryonic autonomic neurons. However, in several respects appearance of differentiated features of the neuroblastoma cells did not follow the pattern observed for normal neurons, suggesting noncoordinate, expression of neuronal phenotypic properties. First, an occasional neuroblastoma cell had as extensive granular endoplasmic reticulum as would be found at later stages in normal developing neurons. Second, the cellular processes of these neuroblastoma cells did not have the fine structure of developing or mature axons in vivo. Third, few dense core vesicles were found in SK-N-SH and SK-N-BE(2), though these organelles are numerous in early normal adrenergic neurons and the adrenergic character of these two lines is apparent from other studies that have demonstrated expression of neurotransmitter synthesizing enzymes (SK-N-MC is cholinergic). The fine structural characterization of these continuous human neuroblastoma cell lines will allow this parameter to be utilized with other approaches in future experimental studies. [ABSTRACT FROM AUTHOR]

This experiment was designed to examine the growth, proportion of stages, and fecundity of an Oesophagostomum dentatum population by transplantation of a known small number of worms from a high-density population into helminth-naive recipient pigs. Approximately 1,500 4-week-old worms [69% fourth-stage larvae (L), 31% adult worms] were transplanted into each of 5 recipient pigs (group B), and these pigs, along with a group of 5 high-level-infection control pigs (group C), were killed at 4 weeks after transplantation to determine and compare the worm burdens. By 2 weeks after transplantation and throughout the experiment, fecal egg counts of group B exceeded those of group C and the fecundity of the worms was higher, though not statistically significantly so, in the transplanted worms. In the recipient pigs, all worms (approx. 70% establishment) had developed to the adult stage and were significantly longer than worms recovered from the group C pigs. [ABSTRACT FROM AUTHOR]