Comparing Efficacy of Guselkumab versus Ustekinumab in Patients with Psoriatic Arthritis: An Adjusted Comparison Using Individual Patient Data from the DISCOVER and PSUMMIT Trials.

INTRODUCTION: Two biologic therapies for psoriatic arthritis (PsA), guselkumab and ustekinumab, have demonstrated superior efficacy versus placebo in clinical trials. However, no head-to-head studies have been conducted comparing these two treatments for PsA. The objective was to indirectly compare guselkumab and ustekinumab on joint and skin efficacy up to week 52, using pooled individual patient-level data (IPD) from PsA trials. METHODS: IPD, including baseline characteristics, American College of Rheumatology (ACR) scores and Psoriasis Area Severity Index (PASI) response from guselkumab (DISCOVER-1 and -2) and ustekinumab (PSUMMIT 1 and 2) trials were pooled. Differences in patient characteristics across trials were adjusted using multivariate logistic regression. Odds ratios (OR) were used to derive absolute response probabilities in the guselkumab trial population and were presented with 95% confidence intervals. RESULTS: Most baseline characteristics for guselkumab-treated patients (100 mg every 8 weeks [Q8W]; 100 mg every 4 weeks [Q4W]) were comparable to ustekinumab-treated patients (45/90 mg). In biologic-naïve patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 1.97; 1.37, 2.84; Q4W: 2.04; 1.40, 2.96) and PASI 90 (Q8W: 2.33; 1.52, 3.56; Q4W: 2.57; 1.67, 3.97) versus ustekinumab from week 16 onwards. In biologic-experienced patients, both guselkumab doses showed significantly higher ACR 20 (Q8W: 2.57; 1.11, 5.93; Q4W: 2.63; 1.12, 6.17) versus ustekinumab from week 24 onwards; for PASI 90, both guselkumab doses were superior to ustekinumab at week 16 and 52 (Q8W: 3.96; 1.39, 11.27; Q4W: 13.10; 4.18, 41.04). Guselkumab efficacy was similar and robust across primary, scenario, and sensitivity analyses. CONCLUSIONS: IPD analysis demonstrated that both guselkumab doses were superior to ustekinumab for ACR 20 from weeks 16 (biologic-naïve) and 24 (biologic-experienced) onwards, and for PASI 90 at weeks 16 and 52 for both subgroups.

Systematic literature review and network meta-analysis of therapies for psoriatic arthritis on patient-reported outcomes.

OBJECTIVES: Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This study describes the relative effectiveness of targeted synthetic (ts) and biologic (b) disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes (PROs) through network meta-analysis (NMA). DESIGN: A systematic literature review (SLR) was conducted in January 2020. Bayesian NMAs were conducted to compare treatments on Health Assessment Questionnaire Disability Index (HAQ-DI) and 36-item Short Form (SF-36) Health Survey including Mental Component Summary (MCS) and Physical Component Summary (PCS) scores. DATA SOURCES: Ovid MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily),Embase and Cochrane Central Register of Controlled Trials. ELIGIBILITY CRITERIA: Phase III randomised controlled trials (RCTs) evaluating patients with PsA receiving tsDMARDS, bDMARDs or placebo were included in the SLR; there was no restriction on outcomes. DATA EXTRACTION AND SYNTHESIS: Two independent researchers reviewed all citations. Data for studies meeting all inclusion criteria were extracted into a standardised Excel-based form by one reviewer and validated by a second reviewer. A third reviewer was consulted to resolve any discrepancies, as necessary. Risk of bias was assessed using the The National Institute for Health and Care Excellence clinical effectiveness quality assessment checklist. RESULTS: In total, 26 RCTs were included. For HAQ-DI, SF-36 PCS and SF-36 MCS scores, intravenous tumour necrosis factor (TNF) alpha inhibitors generally ranked higher than most other classes of therapies available to treat patients with PsA. For almost all outcomes, several interleukin (IL)-23, IL-17A, subcutaneous TNF and IL-12/23 agents offered comparable improvement, while cytotoxic T-lymphocyte-associated antigen 4, phosphodiesterase-4 and Janus kinase inhibitors often had the lowest efficacy. CONCLUSIONS: While intravenous TNFs may provide some improvements in PROs relative to several other tsDMARDs and bDMARDs for the treatment of patients with PsA, differences between classes of therapies across outcomes were small.

Comparative effectiveness of guselkumab in psoriatic arthritis: updates to a systematic literature review and network meta-analysis.

OBJECTIVE: The IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib. MATERIAL AND METHODS: A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). RESULTS: For ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs. CONCLUSIONS: Guselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs.

Comparison of reconstructed prompt gamma emissions using maximum likelihood estimation and origin ensemble algorithms for a Compton camera system tailored to proton range monitoring.

Compton-based prompt gamma (PG) imaging is being investigated by several groups as a potential solution for in vivo range monitoring in proton therapy. The performance of this technique depends on the detector system as well as the ability of the reconstruction method to obtain good spatial resolution to establish a quantitative correlation between the PG emission and the proton beam range in the patient. To evaluate the feasibility of PG imaging for range monitoring, we quantitatively evaluated the emission distributions reconstructed by a Maximum Likelihood Expectation Maximization (MLEM) and a Stochastic Origin Ensemble (SOE) algorithm. To this end, we exploit experimental and Monte Carlo (MC) simulation data acquired with the Polaris-J Compton Camera (CC) prototype. The differences between the proton beam range (RD) defined as the 80% distal dose fall-off and the PG range (RPG), obtained by fitting the distal end of the reconstructed profile with a sigmoid function, were quantified. A comparable performance of both reconstruction algorithms was found. For both experimental and simulated irradiation scenarios, the correlation between RD and RPG was within 5 mm. These values were consistent with the ground truth distance (RD-RPGg≈ 3 mm) calculated by using the expected PG emission available from MC simulation. Furthermore, shifts of 3 mm in the proton beam range were resolved with the MLEM algorithm by calculating the relative difference between the RPG for each reconstructed profile. In non-homogeneous targets, the spatial changes in the PG emission due to the different materials could not be fully resolved from the reconstructed profiles; however, the fall-off region still resembled the ground truth emission. For this scenario, the PG correlation (RD-RPG) varied from 0.1 mm to 4 mm, which is close to the ground truth correlation (3 mm). This work provides a framework for the evaluation of the range monitoring capabilities of a CC device for PG imaging. The two investigated image reconstruction algorithms showed a comparable and consistent performance for homogeneous and heterogeneous targets.

Impact of Physician-Defined Flares on Quality of Life and Work Impairment: An International Survey of 2238 Patients With Psoriatic Arthritis.

OBJECTIVE: To describe psoriatic arthritis (PsA) flares and their effect on patient-reported outcomes (PROs). METHODS: Cross-sectional surveys of rheumatologists/dermatologists and their patients with PsA were conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States, capturing data on physician-reported patient flare status, demographics, PsA severity, and clinical outcomes. Patient-completed surveys captured data on PROs: 5-level EuroQol 5-dimension, Work Productivity and Activity Impairment questionnaire, Health Assessment Questionnaire-Disability Index, and 12-item Psoriatic Arthritis Impact of Disease questionnaire. Patients were compared by flare status using parametric and nonparametric tests. Multivariate regression was used to identify flare associations. Multivariate logistic regression adjusted for patient demographics and physician specialty assessed the effect of flare status. RESULTS: Among 2238 patients (586 from the US, 1652 from Europe) managed by 572 physicians, physician-reported flare was present for 168 patients (7.5%), and self-reported flare was present for 95 patients (10% of available data). Mean (SD) flare count over 12 months was 2.2 (4.9), lasting on average 16.4 (16.2) days. Flare status was linked to worse PROs. Patients who had not flared in the last 12 months or had never flared had a higher quality of life, lower overall work impairment, and a lower degree of disability compared with patients who were currently experiencing a flare (all; P < 0.01). CONCLUSION: Actively experiencing a flare adversely affected QOL, disability, and work productivity. PsA flares should be routinely assessed and managed in clinical care.

Women With Psoriatic Arthritis Experience Higher Disease Burden Than Men: Findings From a Real-World Survey in the United States and Europe.

OBJECTIVE: Although psoriatic arthritis (PsA) is equally present in men and women, sex may influence clinical manifestations and the impact of disease on patients' lives. This study assessed differences in clinical characteristics, disability, quality of life (QOL), and work productivity by sex in real-world practice. METHODS: A cross-sectional survey of rheumatologists/dermatologists and their patients with PsA was conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States between June and August 2018. Data collected included demographics, treatment use, clinical characteristics (tender joint count, swollen joint count, body surface area affected by psoriasis), QOL (EuroQoL 5-Dimension questionnaire [EQ-5D], Psoriatic Arthritis Impact of Disease [PsAID12]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and work productivity (Work Productivity and Impairment Index [WPAI]). Outcomes were compared between men and women using parametric and nonparametric tests, as appropriate. RESULTS: Of 2270 patients (mean age 48.6 [SD 13.3] yrs, mean disease duration 4.9 [SD 6.0] yrs), 1047 (46.1%) were women. Disease duration, disease presentation, and biologic use (mean 54.2%) were comparable between women and men. Women reported worse QOL (EQ-5D: 0.80 [SD 0.2] vs 0.82 [SD 0.2]; P = 0.02), greater disability (HAQ-DI: 0.56 [SD 0.6] vs 0.41 [SD 0.5]; P < 0.01) and work activity impairment (WPAI: 27.9% [SD 22.0] vs 24.6% [SD 22.4]; P < 0.01) than men. However, women had a lower burden of comorbidities (Charlson Comorbidity Index: 1.10 [SD 0.5] vs 1.15 [SD 0.6]; P < 0.01). CONCLUSION: In patients with similar PsA disease activity and treatment, women experienced greater disease impact than men. This represents a significant consideration for the therapeutic management of PsA.

Effect of Fatigue on Health-Related Quality of Life and Work Productivity in Psoriatic Arthritis: Findings From a Real-World Survey.

OBJECTIVE: To evaluate fatigue frequency and severity among patients with psoriatic arthritis (PsA) and assess the effect of fatigue severity on patient-reported outcome measures (PROMs) assessing quality of life, function, and work productivity. METHODS: Data were derived from the Adelphi Disease Specific Programme, a cross-sectional survey conducted in 2018 in the United States and Europe. Patients had physician-confirmed PsA. Fatigue was collected as a binary variable and through its severity (0-10 scale, using the 12-item Psoriatic Arthritis Impact of Disease fatigue question) from patients; physicians also reported patient fatigue (yes/no). Other PROMs included the 5-level EuroQol 5-dimension questionnaire (EQ-5D-5L) for health-related quality of life (HRQOL), Health Assessment Questionnaire-Disability Index, and Work Productivity and Activity Impairment Questionnaire. Multivariate linear regression was used to evaluate the association between fatigue severity and other PROMs. RESULTS: Among the 831 included patients (mean age 47.5 yrs, mean disease duration 5.3 yrs, 46.9% female, 48.1% receiving a biologic), fatigue was reported by 78.3% of patients. Patients with greater fatigue severity had greater disease duration, PsA severity, pain levels, body surface area affected by psoriasis, and swollen and tender joint counts (all P < 0.05). In multivariate analyses, patients with greater fatigue severity experienced worse physical functioning, HRQOL, and work productivity (all P < 0.001). Presence of fatigue was underreported by physicians (reported in only 32% of patients who self-reported fatigue). CONCLUSION: Prevalence of patient-reported fatigue was high among patients with PsA and underrecognized by physicians. Fatigue severity was associated with altered physical functioning, work productivity, and HRQOL.

Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis.

OBJECTIVE: The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA). METHODS: A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs). RESULTS: Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks. CONCLUSIONS: In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.

Expanding Ethanol Production in the United States: The Roles of Policy, Price, and Demand.

Assessments of the impact of the U.S. renewable fuel standard (RFS) should inform consideration of future biofuels policy. Conventional wisdom suggests the RFS played a major role in stimulating the ten-fold expansion in ethanol production and consumption in the United States from 2002 to 2019, but evidence increasingly suggests the RFS might have had a smaller effect than previously assumed. Price competitiveness, federal and state policies such as reformulated gasoline requirements, and octane content in ethanol also affect ethanol market attractiveness. This study explores the roles of policy and economic factors by comparing historical data with results from scenarios simulated in a system dynamics model. Results suggest price competitiveness explains much of the growth in the ethanol industry from 2002 to 2019. The Volumetric Ethanol Excise Tax Credit and phaseout of the oxygenate methyl tert-butyl ether contributed to earlier growth relative to expected timing of growth based on fuel price alone. The RFS (modeled through observed Renewable Identification Numbers [RINs]) contributed to increased ethanol production in later years and may have increased production in the earlier years if risk of investment was decreased.

Computational model for detector timing effects in Compton-camera based prompt-gamma imaging for proton radiotherapy.

This paper describes a realistic simulation of a Compton-camera (CC) based prompt-gamma (PG) imaging system for proton range verification for a range of clinical dose rates, and its comparison to PG measured data with a pre-clinical CC. We used a Monte Carlo plus Detector Effects (MCDE) model to simulate the production of prompt gamma-rays (PG) and their energy depositions in the CC. With Monte Carlo, we simulated PG emission resulting from irradiation of a high density polyethylene phantom with a 150 MeV proton pencil beam at dose rates of 5.0 × 108, 2.6 × 109, and 4.6 × 109 p+ s-1. Realistic detector timing effects (e.g. delayed triggering time, event-coincidence, dead time, etc,) were added in post-processing to allow for flexible count rate variations. We acquired PG emission measurements with our pre-clinical CC during irradiation with a clinical 150 MeV proton pencil beam at the same dose rates. For simulations and measurements, three primary changes could be seen in the PG emission data as the dose rate increased: (1) reduction in the total number of detected events due to increased dead-time percentage; (2) increase in false-coincidence events (i.e. multiple PGs interacting, rather than a single PG scatter); and (3) loss of distinct PG emission peaks in the energy spectrum. We used the MCDE model to estimate the quality of our measured PG data, primarily with regards to true and false double-scatters and triple-scatters recorded by the CC. The simulation results showed that of the recorded double-scatter PG interactions 22%, 57%, and 70% were false double-scatters and for triple-scatter interactions 3%, 21%, and 35% were false events at 5.0 × 108, 2.6 × 109, and 4.6 × 109 p+ s-1, respectively. These false scatter events represent noise in the data, and the high percentage of these events in the data represents a major limitation in our ability to produce usable PG images with our prototype CC.

The multifaceted impact of anxiety and depression on patients with rheumatoid arthritis.

BACKGROUND: The prevalence of mood disturbances such as anxiety and depression is greater in rheumatoid arthritis (RA) patients than in the general population. Given this association, the primary aim of this study was to assess the incremental impact of anxiety or depression on patients with RA from the United States of America (USA) and Europe, independent of the impact of the underlying RA disease. METHODS: Rheumatologists (n = 408) from the USA and 5 European countries completed patient record forms for a predetermined number of RA patients who consulted consecutively during the study period; these patients completed patient-reported questionnaires. Descriptive statistics and multivariate regression were used to investigate the relationship between anxiety and depression with treatment and economic outcomes in RA patients. RESULTS: Of 1015 physician and patient pairs who completed all relevant questionnaire sections, 390 (38.4%) patients self-reported anxiety or depression, while 180 (17.7%) patients were reported to have anxiety or depression by their physicians. Controlling for age, gender, body mass index and clinical factors (flaring and severity), multiple regression analyses suggested that patients with anxiety or depression more often experienced treatment dissatisfaction (odds ratio [OR] 2.28; P < .001), had greater impairment in work (coefficient [ß] = 11.82; P = .001) and usual activity (ß = 14.73; P < .001), greater disability (ß = .35; P < .001), and more often reported unemployment (OR 1.74; P = .001). Multinomial logistic regression revealed discordance between physician and patient satisfaction with treatment. For patients reporting anxiety or depression, physicians were more often satisfied with achievement of current disease control than patients (relative risk ratio 2.19; P = .002). CONCLUSION: Concomitant anxiety or depression was associated with a significant incremental impact on the health-related quality of life and economic aspects of life of patients with RA. In light of observed differences between physician recognition of patient anxiety and/or depression versus patient reporting of anxiety and/or depression symptoms, further research is warranted to develop optimal screening and management of depression and anxiety in patients with RA.

Long-Distance Transportation Causes Temperature Stress in the Honey Bee, Apis mellifera (Hymenoptera: Apidae).

Pollination services provided by the honey bee, Apis mellifera (Hymenoptera: Apidae, Linnaeus, 1758) have broad economic impacts and are necessary for production of a diversity of important crops. Hives may be transported multiple times per year to provide pollination. To test how temperature may contribute to transportation stress, temperature sensors were placed in hives in different locations and orientations on the trailer during shipping. Colony size prior to shipping significantly contributed to loss of population immediately after shipping which contributed to colony failure with smaller colonies more likely to fail and fail faster. Colony size also affects thermoregulation and temperature stress. Internal hive temperature varies significantly based on location and orientation. While colonies near the front and rear of the trailer and those oriented toward the center aisle had significantly different average internal temperatures, colony size best predicts loss of thermoregulation. Additionally, we profiled gene expression at departure, on arrival, and after a recovery period to identify transcriptional responses to transportation. Functional and enrichment analysis identified increased methylation and decreased ribosomal and protein-folding activity. Pheromone and odorant-binding transcripts were up-regulated after transportation. After recovery, transcripts associated with defense response, immune activity, and heat shock decreased, while production of antibiotic peptides increased. We conclude that hives experience considerable temperature stress possibly caused by turbulent airflow in exposed locations. Transportation stress should be considered an important component of annual colony losses which can be mitigated with improved management strategies.

The economic burden of depression among adults with rheumatoid arthritis in the United States.

AIMS: Depression is the most frequent comorbidity reported among patients with rheumatoid arthritis (RA). Comorbid depression negatively impacts RA patients' health-related quality-of-life, physical function, mental function, mortality, and experience of pain and symptom severity. The objective of this study was to assess healthcare utilization, expenditures, and work productivity among patients with RA with or without depression. MATERIALS AND METHODS: Data from adult patients who had at least two visits each related to RA and depression over a 1-year period were extracted from the Truven Health MarketScan research databases. Outcomes comprised healthcare resource utilization, work productivity loss, and direct healthcare costs comparing patients with RA with depression (n = 3,478) vs patients with RA without depression (n = 43,222). RESULTS: Patients with RA and depression had a significantly greater relative risk of hospitalization and number of all-cause and RA-related hospitalizations, utilization of emergency services, days spent in the hospital, physician visits, and RA-related surgeries compared with RA patients without depression. Patients with RA and depression had a higher risk of and experienced more events and days of short-term disability compared with patients without depression. The incremental adjusted annual all-cause and RA-related direct costs were $8,488 (95% CI = $6,793-$10,223) and $578 (95% CI = -$98-$1,243), respectively, when comparing patients with RA and depression vs RA only. LIMITATIONS: The current analysis is subject to the known limitations of retrospective studies based on administrative claims data. CONCLUSIONS: This study suggested increased healthcare utilization, work productivity loss, and economic burden among RA patients due to comorbid depression. These findings emphasize the importance of managing depression and including depression as a factor when devising treatment algorithms for patients with RA.

Penicillium gravinicasei, a new species isolated from cave cheese in Apulia, Italy.

Several species of the genus Penicillium were isolated during a survey of the mycobiota of Apulian cave cheeses ripened in a cave in Gravina di Puglia, Italy. A novel species, Penicillium gravinicasei, is described in Penicillium section Cinnamopurpurea. Its taxonomic novelty was determined using a polyphasic approach, combining phenotypic, molecular (ß-tubulin, calmodulin, ITS and DNA dependent RNA polymerase) DNA sequences and mycotoxin production data. Phylogenetic analyses of the RPB2 data showed that isolates of the novel species form a clade most closely related to Penicillium cinnamopurpureum and P. parvulum with high bootstrap support. The fungus did not produce ochratoxin A, citrinin, patulin, sterigmatocystin or aflatoxin B1 on standard agar media. The novel species had a high growth rate on agar media supplemented with 5% NaCl, and could be distinguished from other Penicillium section Cinnamopurpurea species by phenotypic and molecular characteristics.

Formation of inclusion complexes between high amylose starch and octadecyl ferulate via steam jet cooking.

Amylose-ligand inclusion complexes represent an interesting approach to deliver bioactive molecules. However, ferulic acid has been shown not to form single helical inclusion complexes with amylose from high amylose maize starch. To overcome this problem a lipophilic ferulic acid ester, octadecyl ferulate, was prepared and complexed with amylose via excess steam jet cooking. Jet-cooking octadecyl ferulate and high amylose starch gave an amylose-octadecyl ferulate inclusion complex in 51.0% isolated yield. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) confirmed that a 61 V-type inclusion complex was formed. Amylose and extraction assays showed the complex to be enriched in amylose (91.9±4.3%) and contain 70.6±5.6mgg(-1) octadecyl ferulate, although, minor hydrolysis (∼4%) of the octadecyl ferulate was observed under the excess steam jet-cooking conditions utilized. This study demonstrates that steam jet cooking is a rapid and scalable process in which to prepare amylose-octadecyl ferulate inclusion complexes.

The effects of Doppler broadening and detector resolution on the performance of three-stage Compton cameras.

PURPOSE: The authors investigated how the characteristics of the detectors used in a three-stage Compton camera (CC) affect the CC's ability to accurately measure the emission distribution and energy spectrum of prompt gammas (PG) emitted by nuclear de-excitations during proton therapy. The detector characteristics they studied included the material (high-purity germanium [HPGe] and cadmium zinc telluride [CZT]), Doppler broadening (DB), and resolution (lateral, depth, and energy). METHODS: The authors simulated three-stage HPGe and CZT CCs of various configurations, detecting gammas from point sources with energies ranging from 0.511 to 7.12 MeV. They also simulated a proton pencil beam irradiating a tissue target to study how the detector characteristics affect the PG data measured by CCs in a clinical proton therapy setting. They used three figures of merit: the distance of closest approach (DCA) and the point of closest approach (PCA) between the measured and actual position of the PG emission origin, and the calculated energy resolution. RESULTS: For CCs with HPGe detectors, DB caused the DCA to be greater than 3 mm for 14% of the 6.13 MeV gammas and 20% of the 0.511 MeV gammas. For CCs with CZT detectors, DB caused the DCA to be greater than 3 mm for 18% of the 6.13 MeV gammas and 25% of the 0.511 MeV gammas. The full width at half maximum (FWHM) of the PCA in the z direction for HPGe and CZT detectors ranged from 1.3 to 0.4 mm for gammas with incident energy ranging from 0.511 to 7.12 MeV. For CCs composed of HPGe detectors, the resolution of incident gamma energy calculated by the CC ranged from 6% to 1% for gammas with true incident energies from 0.511 to 7.12 MeV. For CCs composed of CZT detectors, the resolution of gamma energy calculated by the CC ranged from 10% to 1% for gammas with true incident energies from 0.511 to 7.12 MeV. For HPGe and CZT CCs in which all detector effect were included, the DCA was less than 3 mm for 75% and 68% of the detected gammas, respectively, and restricting gammas to those having energy greater than 2.0 MeV increased these percentages to 83% and 77% for HPGe and CZT, respectively. Distributions of the true gamma origins and the PCA after detector characteristics had been included showed good agreement on beam range and some loss of resolution for the lateral profile of the PG emission. Characteristic energy lines were evident in the calculated gamma energy spectrum. CONCLUSIONS: The authors found the following: (1) DB is the dominant source of spatial and energy resolution loss in the CCs at all energy levels; (2) the largest difference in the spatial resolution of HPGe and CZT CCs is that the spatial resolution distributions of CZT have broader tails. The differences in the FWHM of these distributions are small; (3) the energy resolution of both HPGe and CZT three-stage CCs is adequate for PG spectroscopy; and (4) restricting the gammas to those having energy greater than 2.0 MeV can improve the achievable image resolution.

Ethanol distribution, dispensing, and use: analysis of a portion of the biomass-to-biofuels supply chain using system dynamics.

The Energy Independence and Security Act of 2007 targets use of 36 billion gallons of biofuels per year by 2022. Achieving this may require substantial changes to current transportation fuel systems for distribution, dispensing, and use in vehicles. The U.S. Department of Energy and the National Renewable Energy Laboratory designed a system dynamics approach to help focus government action by determining what supply chain changes would have the greatest potential to accelerate biofuels deployment. The National Renewable Energy Laboratory developed the Biomass Scenario Model, a system dynamics model which represents the primary system effects and dependencies in the biomass-to-biofuels supply chain. The model provides a framework for developing scenarios and conducting biofuels policy analysis. This paper focuses on the downstream portion of the supply chain-represented in the distribution logistics, dispensing station, and fuel utilization, and vehicle modules of the Biomass Scenario Model. This model initially focused on ethanol, but has since been expanded to include other biofuels. Some portions of this system are represented dynamically with major interactions and feedbacks, especially those related to a dispensing station owner's decision whether to offer ethanol fuel and a consumer's choice whether to purchase that fuel. Other portions of the system are modeled with little or no dynamics; the vehicle choices of consumers are represented as discrete scenarios. This paper explores conditions needed to sustain an ethanol fuel market and identifies implications of these findings for program and policy goals. A large, economically sustainable ethanol fuel market (or other biofuel market) requires low end-user fuel price relative to gasoline and sufficient producer payment, which are difficult to achieve simultaneously. Other requirements (different for ethanol vs. other biofuel markets) include the need for infrastructure for distribution and dispensing and widespread use of high ethanol blends in flexible-fuel vehicles.

Evaluation of a stochastic reconstruction algorithm for use in Compton camera imaging and beam range verification from secondary gamma emission during proton therapy.

In this paper, we study the feasibility of using the stochastic origin ensemble (SOE) algorithm for reconstructing images of secondary gammas emitted during proton radiotherapy from data measured with a three-stage Compton camera. The purpose of this study was to evaluate the quality of the images of the gamma rays emitted during proton irradiation produced using the SOE algorithm and to measure how well the images reproduce the distal falloff of the beam. For our evaluation, we performed a Monte Carlo simulation of an ideal three-stage Compton camera positioned above and orthogonal to a proton pencil beam irradiating a tissue phantom. Scattering of beam protons with nuclei in the phantom produces secondary gamma rays, which are detected by the Compton camera and used as input to the SOE algorithm. We studied the SOE reconstructed images as a function of the number of iterations, the voxel probability parameter, and the number of detected gammas used by the SOE algorithm. We quantitatively evaluated the capabilities of the SOE algorithm by calculating and comparing the normalized mean square error (NMSE) of SOE reconstructed images. We also studied the ability of the SOE reconstructed images to predict the distal falloff of the secondary gamma production in the irradiated tissue. Our results show that the images produced with the SOE algorithm converge in ~10,000 iterations, with little improvement to the image NMSE for iterations above this number. We found that the statistical noise of the images is inversely proportional to the ratio of the number of gammas detected to the SOE voxel probability parameter value. In our study, the SOE predicted distal falloff of the reconstructed images agrees with the Monte Carlo calculated distal falloff of the gamma emission profile in the phantom to within ±0.6 mm for the positions of maximum emission (100%) and 90%, 50% and 20% distal falloff of the gamma emission profile. We conclude that the SOE algorithm is an effective method for reconstructing images of a proton pencil beam from the data collected by an ideal Compton camera and that these images accurately model the distal falloff of secondary gamma emission during proton irradiation.

Material efficiency studies for a Compton camera designed to measure characteristic prompt gamma rays emitted during proton beam radiotherapy.

Prompt gamma rays emitted from biological tissues during proton irradiation carry dosimetric and spectroscopic information that can assist with treatment verification and provide an indication of the biological response of the irradiated tissues. Compton cameras are capable of determining the origin and energy of gamma rays. However, prompt gamma monitoring during proton therapy requires new Compton camera designs that perform well at the high gamma energies produced when tissues are bombarded with therapeutic protons. In this study we optimize the materials and geometry of a three-stage Compton camera for prompt gamma detection and calculate the theoretical efficiency of such a detector. The materials evaluated in this study include germanium, bismuth germanate (BGO), NaI, xenon, silicon and lanthanum bromide (LaBr(3)). For each material, the dimensions of each detector stage were optimized to produce the maximum number of relevant interactions. These results were used to predict the efficiency of various multi-material cameras. The theoretical detection efficiencies of the most promising multi-material cameras were then calculated for the photons emitted from a tissue-equivalent phantom irradiated by therapeutic proton beams ranging from 50 to 250 MeV. The optimized detector stages had a lateral extent of 10 × 10 cm(2) with the thickness of the initial two stages dependent on the detector material. The thickness of the third stage was fixed at 10 cm regardless of material. The most efficient single-material cameras were composed of germanium (3 cm) and BGO (2.5 cm). These cameras exhibited efficiencies of 1.15 × 10(-4) and 9.58 × 10(-5) per incident proton, respectively. The most efficient multi-material camera design consisted of two initial stages of germanium (3 cm) and a final stage of BGO, resulting in a theoretical efficiency of 1.26 × 10(-4) per incident proton.

A community-based systems learning approach to understanding youth violence in Boston.

BACKGROUND: Youth violence in general and gang violence in particular continues to be a pernicious problem facing the majority of large U.S. cities. Attempts to reduce youth violence are hindered by the absence of a shared framework that crosses multiple disciplines. OBJECTIVE: The goal of the Youth Violence Systems Project (YVSP) is to help communities strategize for and achieve sustained reductions in youth violence in Boston. METHODS: A distinction of YVSP is the engagement of community residents in a group model building process to develop a conceptual framework and create a system dynamics computer model of youth violence in Boston. Community residents including youth participated in the design, execution, and evaluation of the project. We also partnered with community agencies to gain insight from individuals with a history of gang involvement or violent offense. The computer model highlights the dynamics of movement into and out of gangs, and the relationships that influence violent interactions among individuals and gangs. The model serves as a simulation-based laboratory for examining initiatives aimed at reducing youth violence within a community. It considers the positive feedback between traumatic stress and violence; as violence levels rise in the community, this increases individual traumatic stress, which further increases violent responses by community members. CONCLUSION: The project's community-based approach coupled with its system dynamics methodology produced a new understanding of youth violence in Boston. This understanding undergirds the model's logic, making it more useful to community residents and more accurate in describing the behavior of youth in high-violence neighborhoods.