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In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM. Methods: Whole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences. Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBMCT weakly correlated with body mass (men, r² = 0.32; women, r² = 0.22), and thus SUV and SULCT were also weakly correlated (men, r² = 0.24; women, r² = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance. Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials. [ABSTRACT FROM AUTHOR]

Institutional interest in bitcoin has grown significantly since its "bubble highs" in 2017; and given its lack of traditional fundamentals, investor sentiment is likely to drive price discovery. As social media has grown, Reddit has evolved to host significant conversations regarding bitcoin ('r/bitcoin') and general investing ('r/investing'). We focus on these two channels using four distinct natural language processing algorithms to create an ensemble sentiment score and measure the relationship of the score to the change in bitcoin's price. [ABSTRACT FROM AUTHOR]

Purpose: To estimate health utility values, explore predictors of utility values, and estimate the quality-adjusted life years (Q.A.L.Y.s) gained by treatment in multicentric Castleman's disease (M.C.D.).Methods: The SF-36 was administered to 79 patients enrolled in a randomized, double-blind, placebo-controlled, multi-national study to determine the safety and efficacy of siltuximab plus best supportive care (B.S.C.) compared with B.S.C., in subjects with symptomatic M.C.D. Utility (SF-6D) scores were derived from the SF-36. Sensitivity analyses using utilities obtained by mapping the SF-36 to the EQ-5D were also conducted. Repeated measures, mixed effects models were conducted to estimate effects of treatment, responder status and ≥ Grade 3 adverse events (A.E.s) on changes in utility values over time, controlling for baseline utility value. Additionally, differential Q.A.L.Y. gain was assessed in the trial using multiple regression.Results: Patients on siltuximab and those who experienced a complete or partial response had higher mean utility values over time than those on placebo or those with stable disease. After an initial response to treatment, the mean utility remained relatively stable for patients on siltuximab and those who experienced a complete or partial response during the period when most patients were on study. A significantly different Q.A.L.Y. gain was found for patients on siltuximab (versus placebo) as calculated by SF-6D (0.070 Q.A.L.Y.s, p < .05) scores at 6 months (EQ-5D 0.096 Q.A.L.Y.s, p < 0.05).Conclusions: Siltuximab demonstrated improved, durable health utility gains in this rare disease over B.S.C. The main SF-6D results were supported by EQ-5D sensitivity analysis. These findings are limited by the small study sample size and substantial missing data caused predominantly by crossover. A longitudinal, multisite international observational study capturing clinical, safety and health-related quality of life (H.R.Q.L.) endpoints are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective The direct cost of relapsed or refractory multiple myeloma ( RRMM) is documented; indirect costs are being explored. Healthcare payers seek cost-offsets from therapies that improve clinical outcomes but challenge budgets; employers seek lower absenteeism and better productivity. Study goals were to: (i) identify direct and indirect economic factors of RRMM, and (ii) explore longitudinal relationships between clinical, economic, and health-related quality of life ( HRQoL) assessments. Methods Economic questionnaire, clinical, and HRQoL data from a multisite, international, randomized, controlled study in RRMM were analyzed. Results Patients (n=263) were 53.6% male, 91.6% Caucasian; mean age of 62.9 years, median Eastern Cooperative Oncology Group status of 1 (56.3%). Moderate to severe pain or fatigue was reported by 30.4% and 70.6%, respectively. At baseline, ≥1 hospitalization was reported by 107 (41.8%); 182 (71.1%) and 86 (33.6%) reported specialist and family physician visits, respectively. A total of 28 (10.8%) were working: 10 (37.0%) of which reported RRMM-driven absenteeism ≥1 day. Of those who were not working, 110 (48.2%) indicated that it was due to RRMM. Multivariate modeling showed lower hospitalization with a major tumor response (β=−1.44, CI: −2.89 to 0.01, P=.05). Conclusions Substantial RRMM indirect, social costs were observed. Better major tumor response may reduce hospital visits. [ABSTRACT FROM AUTHOR]

This descriptive, cross-sectional analysis evaluated the impact of baseline characteristics on health-related quality of life ( HR-QoL) at different stages of multiple myeloma ( MM). The bortezomib clinical-trial programme evaluated HR-QoL early and consistently, producing a large multi-study dataset. Baseline data, captured using the European Organization for Research and Treatment of Cancer ( EORTC) quality-of-life questionnaire ( QLQ-C30), were pooled from six bortezomib randomized trials conducted in different disease-stage categories: 'New' (previously untreated; n = 753), 'Early' (1-3 prior therapies; n = 1569) and 'Late' (≥4 prior therapies; n = 239) disease. Mean EORTC global health scores were similar across the three stages. Unexpectedly, emotional, physical and role functioning were higher in the later stages, indicating better perceived health. Symptom scores, including pain, were largely similar or lower in the later versus earlier stages, signifying a lower symptom burden/better symptom control with more advanced disease. Notable variation in HR-QoL was observed by age and clinical parameters within and across stages. Multivariate modelling indicated that opioid use and performance status were key factors driving overall HR-QoL across stages. Using an age-restricted analysis, transplant eligibility had little impact on HR-QoL in New disease patients. Thus, changes in HR-QoL over the treatment course of MM are complex and impacted by baseline factors. A prospective observational international inception cohort study that captures key clinical, HR-QoL and demographic characteristics, along with safety and supportive care information, is needed. [ABSTRACT FROM AUTHOR]

This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone ( VTD) and VTD-cyclophosphamide ( VTDC) induction therapy in multiple myeloma. Newly diagnosed patients ( n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m2; days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m2; days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio ( HR) 1·26, 95% confidence interval: 0·76-2·09; P = 0·370]. Five-year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease ( MRD) status, overall survival was longer in MRD-negative versus MRD-positive patients with bone marrow-confirmed complete response ( HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov ( NCT00531453). [ABSTRACT FROM AUTHOR]

Multicentric Castleman disease ( MCD) is a rare lymphoproliferative disease. Little is known about how patient clinical features and healthcare utilization varies by human immunodeficiency virus ( HIV) status and disease subtype. Data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States treatment centres. Clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported by HIV status and cell histology, and statistically compared with the Fisher's Exact and Kruskal-Wallis tests. Patients ( n = 59) had a pathologically and clinically confirmed MCD diagnosis: plasmacytic (42%), hyaline vascular (29%) and mixed (15%); 10% had HIV infection. In the first year after diagnosis, MCD patients on average saw a healthcare provider more than six times, were hospitalized at least once and underwent frequent radiological and laboratory testing. Rituximab was the most commonly used drug therapy, followed by corticosteroids and conventional chemotherapy. One- and 2-year survival was excellent in HIV-negative patients (100% and 97%, respectively) but inferior for HIV-positive cases (67% and 67%, respectively). Heterogeneous treatment decisions were observed in this MCD study; HIV status was the only distinguishing clinical criteria associated with pharmacotherapies. Additional research is necessary to guide treatment of this rare lymphoproliferative disorder. [ABSTRACT FROM AUTHOR]

Multicentric Castleman disease ( MCD) is a rare lymphoproliferative disease with little known about its epidemiology or treatment modalities. Clinical and demographic data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States ( US) MCD referral centres. ZIP codes identified patient residences; prevalence and incidence were estimated based on catchment areas. Patient clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported. MCD patients ( n = 59) were 61% male, mean age of 53 years (median = 55 years) and 68% Caucasian. Of those with known human immunodeficiency virus ( HIV) status ( n = 41), 85% ( n = 35) were negative, 15% ( n = 6) were positive. Most frequent physician-reported symptoms ( n = 33) were fatigue (49%, n = 16), fever (39%, n = 13), and night sweats (30%, n = 10). The estimated US 10-year prevalence was 2·4 per million. During first year of follow-up after study entry, the top two systemic therapies ( n = 27) were monotherapies: prednisone (33%, n = 9) and rituximab (19%, n = 5). After a follow-up of 2 years, 92% of patients were alive. This study provides new information on MCD population demographics, treatment patterns, and medical utilization; a minimal US period prevalence rate is proposed. Study replication is needed to improve external validity. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate intrafractional MR tumor tracking using a prototype linac-MR by delivering radiation to a moving target undergoing simulated tumor motions. Methods: A prototype linac-MR at the Cross Cancer Institute was used for intrafractional MR imaging and simultaneous beam delivery. A Varian 52-leaf MK-II multileaf collimator (MLC) was used for beam collimation. The authors used an inhouse built MR compatible motion phantom to simulate tumor motions during tracking with two different motion patterns (sine and modified cosine). Gafchromic film was inserted in the phantom to measure radiation exposure, and this film measurement was converted to dose (cGy) for further analysis. The authors demonstrated intrafractional tracking in various scenarios: [Scenario 0 (S0)] no phantom motion + no beam margin, (S1) no phantom motion + maximum beam margin, (S2) phantom motion + no beam margin, (S3) S2 + MLC tracking, and (S4) S3 + motion prediction. S0 emulates a perfect tumor tracking scenario, and its result was used as a 'gold-standard' to evaluate tracking accuracy from other scenarios. The authors compared (1) time difference in phantom and MLC motion curves in S3 and S4, and (2) dose profiles (50% beam width, 80%-20% penumbra width) from scenarios S1-S4 to S0. Results: In S4, no observable time difference exists between the phantom and MLC motion curves, indicating that MLC tracks phantom motion accurately. Comparing S4 to S0, 50% beam width reveals minimal differences of < 0.5 mm, while the increase in 80%-20% penumbra width is limited to 0.4 and 1.7 mm in the sine and modified cosine patterns, respectively. Conclusions: The authors report the first demonstration of intrafractional tumor tracking using 2D MR images. During 2 min of tracking, the authors delivered highly conformal dose to a moving target that simulates tumor motions. Compared to static target irradiation, the 50% beam width remains essentially the same (within 0.5 mm), with an increase in 80%-20% penumbra width of less than 1.7 mm in moving target irradiation. These results illustrate potential dosimetric advantages of intrafractional MR tumor tracking in treating mobile tumors as shown for the phantom case. [ABSTRACT FROM AUTHOR]

Tumor volume delineation plays a critical role in radiation treatment planning and simulation. Inaccurately defined target volume may lead to overdosing of normal structures surrounding the tumor, while potentially underdosing cancerous tissue. Conventional 3-dimensional tumor segmentation methods ignore the temporal information present in dynamic Positron Emission Tomography (PET) images and thus may falsely classify equal intensity voxels with completely different time activity curves (TACs) as belonging to the same tissue. We present a novel approach to tumor volume delineation in dynamic PET based on TAC differences. Principal Component Analysis, nonlinear curve-fitting, region growing, and morphological reconstruction are integrated within a single framework for this purpose. A partially-supervised approach is pursued in order to allow an expert reader to utilize the information available from other imaging modalities routinely used in conjunction with PET. In our scheme, this includes the definition of a tumor encompassing mask and selection of a seed site within the suspected tumor, while further delineation is performed by the algorithm automatically. Performance of the proposed algorithm is compared to five other methods. Simulations and a phantom study show that accurate tumor volume delineation can be achieved. [ABSTRACT FROM PUBLISHER]

Objectives The phase 3 VISTA study ( NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone ( VMP; nine 6-wk cycles) vs. melphalan-prednisone ( MP) but also increased toxicity. Health-related quality of life ( HRQoL; exploratory endpoint) was evaluated using the European Organization for Research and Treatment of Cancer ( EORTC) Quality of Life Questionnaire ( QLQ-C30). The phase 3 VISTA study ( NCT00111319) in transplant-ineligible myeloma patients demonstrated superior efficacy with bortezomib-melphalan-prednisone ( VMP; nine 6-wk cycles) vs. melphalan-prednisone ( MP) but also increased toxicity. Health-related quality of life ( HRQoL; exploratory endpoint) was evaluated using the European Organization for Research and Treatment of Cancer ( EORTC) Quality of Life Questionnaire ( QLQ-C30). Methods EORTC QLQ-C30 was administered at screening, on day 1 of each cycle, at the end-of-treatment visit, and every 8 wk until progression. EORTC QLQ-C30 scores were evaluated among patients with a valid baseline and at least one post-baseline HRQoL assessment. Results At baseline, domain scores were similar between arms. By cycle 4, mean differences were clinically meaningful for most domains, indicating poorer health status with VMP. From cycle 5 onwards, improvements relative to baseline/ MP were observed for all domains with VMP. Mean scores were generally improved by the end-of-treatment assessment vs. baseline in both arms. Among responding patients, mean scores generally improved from time of response to end-of-treatment assessment, substantially driven by patients achieving complete response ( CR). Multivariate analysis showed a significant impact of duration of response/ CR on improving global health status, pain, and appetite loss scores. Analyses by bortezomib dose intensity indicated better HRQoL in patients receiving lower dose intensity. Conclusions These findings demonstrate clinically meaningful, transitory HRQoL decrements with VMP and relatively lower HRQoL vs. MP during early treatment cycles, associated with the expected additional toxicities. However, HRQoL is not compromised in the long term, recovering by the end-of-treatment visit to be comparable vs. MP. [ABSTRACT FROM AUTHOR]

Purpose: To address practical issues of implementing artificial neural networks (ANN) for lung-tumor motion prediction in MRI-based intrafractional lung-tumor tracking. Methods: A feedforward four-layered ANN structure is used to predict future tumor positions. A back-propagation algorithm is used for ANN learning. Adaptive learning is incorporated by continuously updating weights and learning rate during prediction. An ANN training scheme specific for MRI-based tracking is developed. A multiple-ANN structure is developed to reduce tracking failures caused by the lower imaging rates of MRI. We used particle swarm optimization to optimize the ANN structure and initial weights (IW) for each patient and treatment fraction. Prediction accuracy is evaluated using the 1D superior-inferior lung-tumor motions of 29 lung cancer patients for system delays of 120-520 ms, in increments of 80 ms. The result is compared with four different scenarios: (1), (2) ANN structure optimization + with/without IW optimization, and (3), (4) no ANN structure optimization + with/without IW optimization, respectively. An additional simulation is performed to assess the value of optimizing the ANN structure for each treatment fraction. Results: For 120-520 ms system delays, mean RMSE values (ranges 0.0-2.8 mm from 29 patients) of 0.5-0.9 mm are observed, respectively. Using patient specific ANN structures, a 30%-60% decrease in mean RMSE values is observed as a result of IW optimization, alone. No significant advantages in prediction performance are observed, however, by optimizing for each fraction. Conclusions: A new ANN-based lung-tumor motion predictor is developed for MRI-based intrafractional tumor tracking. The prediction accuracy of our predictor is evaluated using a realistic simulated MR imaging rate and system delays. For 120-520 ms system delays, mean RMSE values of 0.5-0.9 mm (ranges 0.0-2.8 mm from 29 patients) are achieved. Further, the advantage of patient specific ANN structure and IW in lung-tumor motion prediction is demonstrated by a 30%-60% decrease in mean RMSE values. [ABSTRACT FROM AUTHOR]

Purpose: The first aim of this study is to investigate the feasibility of online autocontouring of tumor in low field MR images (0.2 and 0.5 T) by means of a phantom and simulation study for tumor-tracking in linac-MR systems. The second aim of this study is to develop an MR compatible, lung tumor motion phantom. Methods: An autocontouring algorithm was developed to determine both the position and shape of a lung tumor from each intra fractional MR image. To initiate the algorithm, an expert user contours the tumor and its maximum anticipated range of motion (herein termed the Background) using pretreatment scan data. During treatment, the algorithm processes each intrafractional MR image and automatically contours the tumor. To evaluate this algorithm, the authors built a phantom that replicates the low field contrast parameters (proton density, T1, T2) of lung tumors and healthy lung parenchyma. This phantom allows simulation of MR images with the expected lung tumor CNR at 0.2 and 0.5 T by using a single 3 T scanner. Dynamic bSSFP images (approximately 4 images per second) are acquired while the phantom undergoes a series of preprogrammed motions based on patient lung tumor motion data. These images are autocontoured off-line using our algorithm. The fidelity of autocontouring is assessed by comparing autocontoured tumor shape and its centroid position to the actual tumor shape and its position. Results: The algorithm successfully contoured the shape of a moving tumor model from dynamic MR images acquired every 275 ms. Dice's coefficients of > 0.96 and > 0.93 are achieved in 0.5 and 0.2 T equivalent images, respectively. Also, the algorithm tracked tumor position during dynamic studies, with root mean squared error (RMSE) values of < 0.55 and < 0.92 mm for 0.5 and 0.2 T equivalent images, respectively. Autocontouring speed is approximately 5 ms for each image. Conclusions: Dice's coefficients of > 0.96 and > 0.93 are achieved between autocontoured and real tumor shapes, and the position of a tumor can be tracked with RMSE values of < 0.55 and < 0.92 mm in 0.5 and 0.2 T equivalent images, respectively. These results demonstrate the feasibility of lung tumor autocontouring in low field MR images, and, by extension, intrafractional lung tumor tracking with our laboratory's linac-MR system. [ABSTRACT FROM AUTHOR]

Objective: Large, population-based assessments of systemic sclerosis (SSc) prevalence and comorbidity in the United States (US) are rare. We explored autoimmune disease and other comorbidity patterns among SSc patients in the US from 2001 to 2002 and compared these with controls.Research Design and Methods: Two US datasets with patient-level medical and drug claims were used to assess SSc prevalence and comorbidity: IMS Health Integrated Administrative Claims Database (IMS Health) and the MarketScan Commercial Claims and Encounters Database (MarketScan). SSc patients and comorbidities were identified by International Classification of Diseases (ICD), 9th revision diagnostic codes appearing on medical claims. Patients without SSc diagnostic codes (controls) were selected and matched 4:1 to SSc patients based on sex, age, Census Bureau region, and previous insurance coverage. The prevalence relative risk (RR) statistic compared comorbidity occurrence between SSc patients and controls, with 95% confidence intervals estimated using the Mantel-Haenszel method. Several sensitivity analyses tested methods used for identifying SSc cases and the prevalence of comorbidities.Results: In both databases, SSc prevalence was 0.05% using the standard population model, 0.03% under sensitivity analysis. Among SSc patients the risks for inflammatory bowel disease (IBD) and multiple sclerosis (MS) were notably higher across datasets than for those without SSc: RR 3.2-6.6 for MS, RR 2.1-2.2 for IBD, in MarketScan and IMS Health, respectively (p < 0.05 for all). The chronic disease burden of SSc patients was much higher than that of controls, as confirmed by two chronicity measures (Chronic Disease Score, Elixhauser Comorbidity Index). The risks for cardiovascular, renal, liver and several neuropsychiatric diseases were higher for SSc patients across both datasets. Sensitivity analyses supported these findings.Conclusions: These data provide a population-based estimate of US prevalence of SSc and document the higher risk for certain other autoimmune diseases among SSc patients when compared to controls. Patients with SSc also had a higher chronic disease burden than those without SSc. These findings are limited by the unknown validity of ICD-9 codes for SSc case identification, unbalanced regional representation, and a likely 'healthy worker' effect in these databases. [ABSTRACT FROM AUTHOR]

The purpose of this work is to create a rigorous method of segmenting PET images using an automated iterative technique. To this end a phantom study employing spherical targets was used to determine local (slice specific) threshold levels which produce correct cross-sections based on the contrast between target and background. Numerous target to background activity concentration ratios were investigated but found to have minimal effect in comparison to the influence of target size. Functions were fit to this data and used to construct an iterative threshold segmentation algorithm. In all cases this approach yielded convergence within ten iterations. Iterative threshold segmentation was applied using both an axial and tri-axial approach to the spherical targets and also to two irregularly shaped volumes. Of these two approaches, the tri-axial method proved less susceptible to image noise and better at dealing with partial volume effects at the interface between target and background. For comparative purposes, single thresholds of 28% and 40% were also applied to the spherical data sets. The tri-axial iterative method was found capable of delineating cross sections with areas greater than 250 mm2 to within the maximum resolution possible (1 pixel width). Cross sections of less than 250 mm2 in area were resolved by the tri-axial method to within 2 pixel widths of their true physical extent. Local contrast based iterative threshold segmentation shows promise as a method of rigorously delineating PET target volumes with good accuracy subject to the limitations imposed by the image resolution which currently characterizes this modality. [ABSTRACT FROM AUTHOR]

Focuses on the keys to a successful strategy execution of business transactions in the United States. Ability of communicating the essence of strategic plans; Importance of knowledge in managing business enterprises; Mechanism of progress management.

Argues against Jeffrey Bub's defense of idealization as the way to evolve superselection rules for solving the measurement problem in standard quantum mechanics. Idealization as assuming that measuring apparatus used to measure quantum systems consist of infinite quantum systems; Summary of Bub's defense and corresponding arguments; Falsity of infinity assumption; Prospects of similar proposals.

Richard Healey has recently defended an interactive and holistic interpretation of quantum mechanics. The present work focuses on the holistic aspects of this interpretation. Healey claims that symmetric causes are responsible for the experimental violations of the Bell inequalities and that relational holism is a metaphysical implication of these violations. Presented in this way, the holistic features of Healey's interpretation appear to provide metaphysical backing to the physical mechanism of symmetric causes. It is argued that relational holism is not a metaphysical implication at all but is actually a physical component of Healey's interpretation. Seen in this light, Healey's interpretation no longer appears to provide further insight into the violations of the Bell inequalities. [ABSTRACT FROM PUBLISHER]

A search procedure is presented for discrete-valued dynamic programming problems with the objective of minimizing the sum of convex function This procedure may be more efficient than available methods if the sum is to be minimized over a uniform grid of values of the state variable. Furthermore, the procedure can be used to reduce the computational effort if only some of the return functions have a special structure. [ABSTRACT FROM AUTHOR]

To solve the problem of time-cost tradeoff in project management with available models, a choice must be made between heuristic approaches and algorithms based upon restrictive assumptions about the shape of the cost-time functions of the activities. The algorithm presented in this article involves a dynamic-programming approach to determine the allocation which minimizes the duration of the project (critical path). The main advantage of this model is its ability to determine the optimum allocation among activities with arbitrary cost-time functions. Also, computational shortcuts for functions with special properties can be used to increase the efficiency of the model. Objective functions of networks with special structures decompose into sequences of one-dimensional optimization problems. Although some complex networks have objective functions which cannot be fully decomposed, the dimensions of these functions are considerably less than the number of activities involved. If the activities have nonincreasing cost-time functions, an optimal policy can be used to eliminate the usual search procedure for one-dimensional problems which involve minimizing the maximum of stage returns. [ABSTRACT FROM AUTHOR]

Aims: Studies have shown that bortezomib retreatment is effective in relapsed/refractory multiple myeloma (MM). The observational, prospective electronic VELCADE® OBservational Study (eVOBS) study assessed bortezomib‐based therapies for patients with MM in everyday practice. Here, we report on those patients receiving retreatment with bortezomib. Methods: Consenting adults scheduled to receive bortezomib for MM were enrolled at 162 sites across Europe, Canada, Brazil, Russia, and Turkey between 2006 and 2010. Retrospective data on prior therapies and prospective observational data after bortezomib initiation were captured electronically at baseline, after every bortezomib cycle, and every 12 weeks after discontinuation or progression. Investigator‐assessed responses and adverse events (AEs) were evaluated. Results: Ninety‐six of 873 patients enrolled to eVOBS received bortezomib as first retreatment for progressive disease during the prospective observation period. Median age was 62 years, 53% were male, and median number of prior therapies at retreatment was 4. Overall, 41% of patients initiated bortezomib retreatment in combination with dexamethasone, 16% in combination with lenalidomide, and 21% received monotherapy. Rate of partial response or better (≥PR) was 75% at initial bortezomib therapy, including 44% complete response (CR)/near CR (nCR); at retreatment, ≥PR rate was 46%, including 15% CR/nCR. Median progression‐free survival was 11.4 months (95% confidence interval [CI]: 9.1‐12.7) from start of initial bortezomib treatment and 6.4 months (95% CI: 4.4‐7.2) from start of retreatment. Median overall survival from start of retreatment was 17.6 months (95% CI: 14.4‐23.5). Of the 96 patients retreated with bortezomib, 77% reported an AE. Peripheral neuropathy during bortezomib retreatment occurred in 49% of patients, including 10% grade 3/4. Conclusion: These data suggest that retreatment with bortezomib is a feasible option for patients with relapsed/refractory MM. [ABSTRACT FROM AUTHOR]

The article reports on the arguments made against physcialism by philosophers Tim Crane and D.H. Mellor. Crane and Mellor state that the empirical world contains a picture of true physical science, and mental properties and facts are really physical science. However the author criticizes Crane and Mellor arguments as just properties and uses philosopher Donald Davidson's theory on supervenience physicalist to explain his that point that an event can be described in mental or physical terms.