Sustainable drainage systems (SuDS) could be made better for biodiversity and local people with the help of two new evaluation methods presented by a recent study. The methods, which assess the value of SuDS sites for wildlife habitat, carbon sequestration, recreation and education, are described by the study’s authors as cost-effective, quick and reliable, and could help designers plan and retrofit SuDS that are wildlife-friendly and socially inclusive.

The use of two methods to systematise evidence-evaluation methods is reviewed in nine EU regulations dealing with chemicals risk assessment. The majority of frameworks were found to promote the use of ‘weight of evidence’ or ‘systematic review’-style approaches, but the study found a lack of structured, consistent and detailed guidance for these approaches. The researchers recommend this guidance is developed collaboratively by European regulatory agencies and points to best practice for this guidance.

The Mesothelioma Compensation Center's top priority is seeing to it that a power plant worker with mesothelioma in any state receives the best compensation and to get the job done they recommend attorney Erik Karst of the law firm Karst von Oiste.

MDBerry is a New York-based company providing medical marijuana cards via an online, streamlined process.

Leading educational research firm announces formation of a group dedicated to providing independent, third-party, reviews of research studies

Are your employee reviews focused on improving your company and your team?

Margaret Parker, MD, MCCM, speaks with Katherine J. Steineck, PharmD, pediatric clinical pharmacist at the University of Minnesota Amplatz

We describe a food-based system for quantitatively evaluating habitat quality for deer called the Forage Resource Evaluation System for Habitat and provide its rationale and suggestions for use. The system was developed as a tool for wildlife biologists and other natural resource managers and planners interested in evaluating habitat quality and, especially, comparing two or more patches of habitat or the same patch at different seasons or under different conditions. It is based on the quantity (of biomass) and quality (digestible energy and digestible protein) of the habitat's food resources in relation to user-specified metabolic requirements of deer (which differ with species, age, sex, season, and reproductive status). It uses a linear programming algorithm to determine the suitable forage that can sustain deer at the specified requirements.

Biomass resources in Alaska are extensive and diverse, comprising millions of acres of standing small-diameter trees, diseased or dead trees, and trees having lowgrade timber.

In recent years, interest has increased in restoring Oregon white oak (Quercus garryana Dougl. ex Hook.) and prairie landscapes in the Pacific Northwest, especially where elements of historical plant communities are intact. We evaluated the effect of alternative management scenarios on the extent and condition of Oregon white oak, the extent of prairie, and the harvest and standing volumes of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) within a 2934-ha portion of Fort Lewis, Washington (named the Tenalquot Planning Area for the purpose of the project). A landscape-level analysis of the scenarios was completed using a geographic information system, a forest growth model (ORGANON), and landscape visualization software (EnVision). The scenarios ranged from no active management to restoration of the historical extent of oak and prairies within the planning area. The results indicate that the window of opportunity for restoring oak and prairie landscapes in the Puget Sound lowlands and other regions is small, and aggressive management is needed to maintain or enhance these landscapes. The project demonstrates the value of landscape level analyses and the use of new technologies for conveying the results of alternative management scenarios.

Many stands in southeast Alaska harvested since 1950, especially where there has been a high degree of disturbance of mineral soil, have regenerated to red alder (Alnus rubra Bong.) and are now approaching maturity. The availability of red alder raises questions addressed in this study about the recovery of lumber from this resource. Information in this study was obtained from trees estimated to be 46 years old on a site outside of Ketchikan. Rates of recovery using a thin-kerf portable band mill were higher than those reported by larger production mills in Washington and Oregon. Grade yields of the Alaska material are comparable to those attained in other regions. This study determined that there were no significant differences in material characteristics that would set this Alaska log resource apart from red alder in the other regions of North America. The potential value of the products is sufficient to allow production in Alaska for use in the manufacturing of value-added products within the state or shipment of finished lumber to domestic or export markets.

The Aquatic Conservation Strategy (ACS) of the Northwest Forest Plan guides management of riparian and aquatic ecosystems on federal lands in western Oregon, western Washington, and northern California.

In dry, open coniferous forests of the montane West, stand-replacing wildfires and land use activities alter the composition and abundance of native grasses and forbs by degrading the habitat and accelerating the invasion of exotic annuals. On these lands, native forbs and grasses delayed or prevented from recovery by natural processes may require intervention through supplementary seeding. However, effective seeding of native plants requires that their seed traits and the potential outcome of the seeding be better understood.

Human visual attention is a complex phenomenon. A computational modeling of this phenomenon must take into account where people look in order to evaluate which are the salient locations (spatial distribution of the fixations), when they look in those locations to understand the temporal development of the exploration (temporal order of the fixations), and how they move from one location to another with respect to the dynamics of the scene and the mechanics of the eyes (dynamics). State-of-the-art models focus on learning saliency maps from human data, a process that only takes into account the spatial component of the phenomenon and ignore its temporal and dynamical counterparts. In this work we focus on the evaluation methodology of models of human visual attention. We underline the limits of the current metrics for saliency prediction and scanpath similarity, and we introduce a statistical measure for the evaluation of the dynamics of the simulated eye movements. While deep learning models achieve astonishing performance in saliency prediction, our analysis shows their limitations in capturing the dynamics of the process. We find that unsupervised gravitational models, despite of their simplicity, outperform all competitors. Finally, exploiting a crowd-sourcing platform, we present a study aimed at evaluating how strongly the scanpaths generated with the unsupervised gravitational models appear plausible to naive and expert human observers.

Similarity measure, also called information measure, is a concept used to distinguish different objects. It has been studied from different contexts by employing mathematical, psychological, and fuzzy approaches. Image steganography is the art of hiding secret data into an image in such a way that it cannot be detected by an intruder. In image steganography, hiding secret data in the plain or non-edge regions of the image is significant due to the high similarity and redundancy of the pixels in their neighborhood. However, the similarity measure of the neighboring pixels, i.e., their proximity in color space, is perceptual rather than mathematical. This paper proposes an interval type 2 fuzzy logic system (IT2 FLS) to determine the similarity between the neighboring pixels by involving an instinctive human perception through a rule-based approach. The pixels of the image having high similarity values, calculated using the proposed IT2 FLS similarity measure, are selected for embedding via the least significant bit (LSB) method. We term the proposed procedure of steganography as IT2 FLS LSB method. Moreover, we have developed two more methods, namely, type 1 fuzzy logic system based least significant bits (T1FLS LSB) and Euclidean distance based similarity measures for least significant bit (SM LSB) steganographic methods. Experimental simulations were conducted for a collection of images and quality index metrics, such as PSNR, UQI, and SSIM are used. All the three steganographic methods are applied on datasets and the quality metrics are calculated. The obtained stego images and results are shown and thoroughly compared to determine the efficacy of the IT2 FLS LSB method. Finally, we have done a comparative analysis of the proposed approach with the existing well-known steganographic methods to show the effectiveness of our proposed steganographic method.

Neural networks have opened up many new opportunities to utilize remotely sensed images in meteorology. Common applications include image classification, e.g., to determine whether an image contains a tropical cyclone, and image translation, e.g., to emulate radar imagery for satellites that only have passive channels. However, there are yet many open questions regarding the use of neural networks in meteorology, such as best practices for evaluation, tuning and interpretation. This article highlights several strategies and practical considerations for neural network development that have not yet received much attention in the meteorological community, such as the concept of effective receptive fields, underutilized meteorological performance measures, and methods for NN interpretation, such as synthetic experiments and layer-wise relevance propagation. We also consider the process of neural network interpretation as a whole, recognizing it as an iterative scientist-driven discovery process, and breaking it down into individual steps that researchers can take. Finally, while most work on neural network interpretation in meteorology has so far focused on networks for image classification tasks, we expand the focus to also include networks for image translation.

Techniques for evaluation and/or retraining of a classification model built using labeled training data. In some aspects, a classification model having a first set of weights is retrained by using unlabeled input to reweight the labeled training data to have a second set of weights, and by retraining the classification model using the labeled training data weighted according to the second set of weights. In some aspects, a classification model is evaluated by building a similarity model that represents similarities between unlabeled input and the labeled training data and using the similarity model to evaluate the labeled training data to identify a subset of the plurality of items of labeled training data that is more similar to the unlabeled input than a remainder of the labeled training data.

Methods and apparatus are provided for evaluating potential resource capacity in a system where there is elasticity and competition between a plurality of containers. A dynamic potential capacity is determined for at least one container in a plurality of containers competing for a total capacity of a larger container. A current utilization by each of the plurality of competing containers is obtained, and an equilibrium capacity is determined for each of the competing containers. The equilibrium capacity indicates a capacity that the corresponding container is entitled to. The dynamic potential capacity is determined based on the total capacity, a comparison of one or more of the current utilizations to one or more of the corresponding equilibrium capacities and a relative resource weight of each of the plurality of competing containers. The dynamic potential capacity is optionally recalculated when the set of plurality of containers is changed or after the assignment of each work element.

A proposed feature vector for a first deign is received and an existing feature vector for an existing design is retrieved for a given task. The proposed design is evaluated against the existing design using task-based scores associated with each design and based on their performances for the given task.

A portable, tabletop fluid sampling device simplifies spectral analysis to produce an accurate but inexpensive chromatic fingerprint for fluid samples. In one embodiment, the sampling device uses an array of variable wavelength LED emitters and photodiode detectors to measure Rayleigh scattering of electromagnetic energy from the fluid sample contained in a cuvette. Either the fluid itself, or particles suspended in the fluid can then be identified by performing spectral pattern matching to compare results of a spectral scan against a library of known spectra. A wide range of applications include substance identification, security screening, authentication, quality control, and medical diagnostics.

A system and method for nodule boundary visualization superimposed on a scan image, including generating phantom image measurements of at least one synthetic calibration object in relation to a body to calibrate a scanner; acquiring a first image of a nodule on the calibrated scanner; computing and marking a boundary on the image; displaying the first image with the boundary superimposed over the first image; presenting the initial boundary to a user for modification where the user can add one or more modification points to the image to create a modified boundary that is encompassed by the one or more modification points; once the user has marked the one or more modification points on the image, computing an updated boundary that adapts to include the new points.

Device (10) for vehicle driving evaluation comprising: A means (11) to obtain at least one physical parameter whereby it possible at any time to determine the value of the speed and instantaneous acceleration of a traveling vehicle;A calculation and comparison unit (12) whereby it is possible, from said physical parameter, to calculate an effective parameter that depends on said instantaneous acceleration and to compare said effective parameter with a reference parameter;A driving evaluation unit (13), whereby it is possible to generate a vehicle driving energy score by measuring the variance between said effective parameter and said reference parameter. Corresponding vehicle driving evaluation process.

Provided is a method for simply evaluating defects caused in interface states in oxide semiconductor thin films and protective films in TFTs having protective films formed on the surface of oxide semiconductor thin films without actually measuring the characteristics of the same. This evaluation method evaluates defects caused in the interface states by measuring electron states in the oxide semiconductor thin film by a contact method or noncontact method. The defects caused in the interface states are any of the following (1)-(3). (1) Threshold value voltage (Vth,) when a positive bias is applied to the thin-film transistor(2) Difference in threshold value voltage (ΔVth) before and after applying the positive bias to the thin-film transistor(3) Threshold value during the first measurement when a plurality of measurements is made of the threshold value voltage when a positive bias is applied to the thin-film transistor.

Methods for multiplexed delivery of agents to a solid tissue in vivo followed by assessment of efficacy with mass spectrometry are described.

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In 2013-15, the Scottish Government funded 16 projects proposed by criminal justice partners across Scotland to develop community services for women who offend. Developments were based on existing service provision and to ensure changes could be sustained locally at the end of the funding. Funding varied in amount and timeframes. Most of the projects were undertaken by local authority criminal justice social work1 (CJSW) departments with partner providers, including public and third sector agencies. The national evaluation examined how the 16 women’s community justice services (WCJSs) were implemented and to what extent they contributed towards positive outcomes for women. A further aim was to build local capacity for self-evaluation in WCJSs. Findings were drawn from two phases of interviews with practitioners and women, secondary documents, and quantitative data for 1,778 women who were in the WCJSs between April and December 2014. This included outcomes data for 406 women.

This evaluation report is based on feedback from people living with dementia and carers who received an Individual Award from the Life Changes Trust. The Individual Awards Pilot Scheme was run in Argyll & Bute and Edinburgh in 2014-15 and aimed to provide a small amount of additional financial empowerment to a number of individuals whose lives have been affected by dementia, to help improve their well-being and quality of life. A secondary aim of the pilot scheme was to find out what people would spend the Award on when given relatively broad choice, and what benefit that might bring in the short and medium terms.

Evaluation report for the inter-authority learning exchange between Shetland Islands, Falkirk and Glasgow Councils throughcare and aftercare teams. In February 2014 a member of the Throughcare and Aftercare team from Shetland, spent two weeks in each host authority as a means of developing and sharing practice, experience and learning. The report describes the planning process, in-situ experience, and post-exchange learning of participants, it also report highlights the positive learning outcomes and benefits achieved for all participating local authorities. The report identifies ideas for future applications of such a learning and practice exchange model to improve practice for looked after young people and care leavers.

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

Yu. S. Mishura and H. S. Zhelezniak
Theor. Probability and Math. Statist. 99 (2020), 199-210.
Abstract, references and article information

Last month a friend in the history department passed along a notice from the American Historical Association entitled “AHA Signs onto ASA Statement on Teaching Evaluations.” This ASA is the American Sociological Association, and their statement is a devastating takedown … Continue reading →

Ryan A. Ristau
Nov 1, 2013; 26:211-215
From Research to Practice

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

¹⁸F-PI-2620 is a next generation tau positron emission tomography (PET)-tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry and quantitative methods of ¹⁸F-PI-2620 in the human brain. Full kinetic modelling approaches to quantify tau load were investigated. Non-invasive kinetic modeling approaches and semi-quantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HC) and 4 Alzheimer disease (AD) subjects underwent two dynamic PET scans including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (2 Tissue Compartment (2TC) models, Logan Graphical Analysis (LGA)) and non-invasive kinetic models (Non-Invasive Logan Graphical Analysis (NI-LGA) and the multilinear reference tissue model (MRTM2)). Standardized uptake value ratio (SUVR) was determined at different imaging windows after injection. Correlation between DVR and SUVR, effect size (Cohen’s d) and test-retest variability (TRV) were evaluated. Additionally, 6 HC subjects received one tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: Strong correlation was found across different kinetic models (R2 >0.97) and between DVR(2TC) and SUVRs between 30 to 90 min with R2>0.95. Secular equilibrium was reached around 40 min post injection (p.i.) in most regions and subjects. The TRV and effect size for the SUVR across different regions was similar at 30-60 min (TRV=3.8%, d=3.80), 45-75 min (TRV=4.3%, d=3.77) and 60-90 min (TRV=4.9%, d=3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary system. The whole-body effective dose was determined to be 33.3±2.1 μSv/MBq for an adult female and 33.1±1.4 μSv/MBq for an adult male with a 1.5 hour urinary bladder voiding interval. Conclusion: ¹⁸F-PI-2620 exhibits fast kinetics, suitable dosimetry and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2 and SUVR. SUVR can be used for ¹⁸F-PI-2620 PET quantification of tau deposits avoiding arterial blood sampling. Static ¹⁸F-PI-2620 PET scans between 45-75min p.i. provide excellent quantification accuracy, large effect size and low TRV.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immuno-chemotherapy after two cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying two different methods of interpretation: the Deauville visual five-point scale (5-PS) and a change in standardised uptake value by semi-quantitative evaluation. Methods: 145 patients with newly diagnosed DLBCL underwent pre-treatment PET (PET-0) and PET-2 assessment. PET-2 was classified according to both the visual 5-PS and percentage SUV changes (SUV). Receiver operating characteristic (ROC) analysis was performed to compare the accuracy of the two methods for predicting progression-free survival (PFS). Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET–) groups and compared. Results: Both with visual and SUV-based evaluations significant differences were found between the PFS of iPET– and iPET+ patient groups (p<0.001). Visually the best negative (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if Deauville score 4-5 (89% and 59%, respectively). Using the 66% SUV cut-off value, reported previously, NPV and PPV were 80 and 76%, respectively. SUV at 48.9% cut-off point, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). Visual and semi-quantitative SUV<48.9% assessment of each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100% respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL, iPET had good prognostic value interpreted either visually or semi-quantitatively. We determined that the most effective SUV cut-off was at 48.9%, and that when combined with visual 5-PS assessment, a positive PET-2 was highly predictive of treatment failure.

[S-Methyl-¹¹C](±)-7-methoxy-3-(4-(4-(methylthio)phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol (¹¹C-NR2B-SMe) and its enantiomers were synthesized as candidates for imaging the NR2B subunit within the N-methyl-D-aspartate receptor with positron emission tomography (PET). Methods: Brains were scanned with PET for 90 min after intravenous injection of one of the candidate radioligands into rats. To detect any NR2B specific binding of radioligand in brain, various pre-blocking or displacing agents were evaluated for their impact on the PET brain imaging data. Radiometabolites from brain and other tissues were measured ex vivo and in vitro. Results: Each radioligand gave high early whole brain uptake of radioactivity, followed by a brief fast decline and then a slow final decline. ¹¹C-(S)-NR2B-SMe was studied extensively. Ex vivo measurements showed that radioactivity in rat brain at 30 min after radioligand injection was virtually unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. High-affinity NR2B ligands, Ro-25-6981, ifenprodil, and CO10124, showed increasing preblock of whole brain radioactivity retention with increasing dose (0.01 to 1.25 mg/kg, i.v.). Five 1 antagonists (FTC146, BD1407, F3, F4, and NE100) and four 1 agonists ((+)-pentazocine, (±)-PPCC, PRE-084, (+)-SKF10047) were ineffective preblocking agents, except FTC146 and F4 at high dose. Two potent 1 receptor agonists, TC1 and SA4503, showed dose-dependent preblocking effects in the presence or absence of pharmacological 1 receptor blockade with FTC146. Conclusion: ¹¹C-(S)-NR2B-SMe has adequate NR2B-specific PET signal in rat brain to warrant further evaluation in higher species. TC1 and SA4503 likely have off-target binding to NR2B in vivo.

We aimed to evaluate the diagnostic performance of ¹⁸F-FDG PET/CT for the detection of post-transplantation lymphoproliferative disorder (PTLD) in a pediatric population and explore its feasibility during response assessment. Methods: This retrospective study included 28 pediatric transplant recipients who underwent a total of 32 ¹⁸F-FDG PET/CT scans due to clinical suspicion of PTLD within an 8-year period. Pathology reports and 2-year follow-up were used as reference standard. Twenty-one response assessment ¹⁸F-FDG PET/CT scans were re-evaluated according to the Lugano criteria. Results: The diagnosis of PTLD was established in 14 patients (49%). Sensitivity, specificity, positive predictive value, and negative predictive value of ¹⁸F-FDG PET/CT for the detection of PTLD in children with a clinical suspicion of this disease, was 50% (7/14), 100% (18/18), 100% (7/7), and 72% (18/25), respectively. False-negative results occurred in patients with PTLD in the Waldeyer’s ring, cervical lymph nodes or small bowel with either non-destructive or polymorphic PTLD. Two of 5 interim ¹⁸F-FDG PET/CT scans and 3 of 9 end-of-treatment ¹⁸F-FDG PET/CT scans were false-positive. Conclusion: ¹⁸F-FDG PET/CT had good specificity and positive predictive value but low to moderate sensitivity and negative predictive value for the detection of PTLD in a 28 pediatric patient cohort with a clinical suspicion of this disease. False-negative results were confirmed in the Waldeyer’s ring, cervical lymph nodes and small bowel with either non-destructive or polymorphic PTLD subtypes. ¹⁸F-FDG PET/CT appears to have a limited role in the response assessment setting of pediatric PTLD, given the observed high proportions of false-positives both at interim and end-of-treatment evaluations.

Respiratory gating is the standard to overcome respiration effects degrading image quality in positron emission tomography (PET). Data-driven gating (DDG) using signals derived from PET raw data are promising alternatives to gating approaches requiring additional hardware. However, continuous bed motion (CBM) scans require dedicated DDG approaches for axially-extended PET, compared to DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort, comparing it to hardware-based gating using gated and fully motion-corrected reconstructions. Methods: 56 patients with suspected malignancies in thorax or abdomen underwent whole-body ¹⁸F-FDG CBM-PET/CT imaging using DDG and hardware-based respiratory gating (pressure-sensitive belt gating, BG). Correlation analyses were performed on both gating signals. Besides static reconstructions, BG and DDG were used for optimally-gated PET (BG-OG, DDG-OG) and fully motion-corrected PET (elastic motion correction; BG-EMOCO, DDG-EMOCO). Metabolic volumes, SUV_max and SUVmean of lesions were compared amongst the reconstructions. Additionally, the quality of lesion delineation in different PET reconstructions was independently evaluated by three experts. Results: Global correlation coefficients between BG and DDG signals amounted to 0.48±0.11, peaking at 0.89±0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO and DDG-EMOCO compared to static images (P<0.001; median SUV_max: static, 14.3±13.4; BG-EMOCO, 19.8±15.7; DDG-EMOCO, 20.5±15.6; BG-OG, 19.6±17.1; DDG-OG, 18.9±16.6). No significant differences between BG-OG and DDG-OG, and BG-EMOCO and DDG-EMOCO, respectively, were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P<0.001); no significant difference was found comparing BG and DDG (EMOCO, OG, respectively). Conclusion: DDG-based motion-compensation of CBM-PET acquisitions outperforms static reconstructions, delivering qualities comparable to hardware-based approaches. The new algorithm may be a valuable alternative for CBM-PET systems.

Recently, N-(4-¹⁸F-fluorobenzoyl)-interleukin-2 (¹⁸F-FB-IL2) was introduced as PET tracer for T-cell imaging. However, production is complex and time-consuming. Therefore, we developed two radiolabeled interleukin-2 (IL-2) variants, namely aluminum ¹⁸F-fluoride-(restrained complexing agent)-IL-2 (¹⁸F-AlF-RESCA-IL2) and ⁶⁸Ga-gallium-(1,4,7-triazacyclononane-4,7-diacetic acid-1-glutaric acid)-IL-2 (⁶⁸Ga-Ga-NODAGA-IL2) and compared their in-vitro and in-vivo characteristics with ¹⁸F-FB-IL2. Methods: Radiolabeling of ¹⁸F-AlF-RESCA-IL2 and ⁶⁸Ga-Ga-NODAGA-IL2 was optimized and stability was evaluated in human serum. Receptor binding was studied with activated human peripheral blood mononuclear cells (hPBMCs). Ex-vivo tracer biodistribution in immunocompetent BALB/cOlaHsd (BALB/c) mice was performed at 15, 60 and 90 min after tracer injection. In-vivo binding characteristics were studied in severe combined immune-deficient (SCID) mice inoculated with activated hPBMCs in Matrigel. Tracer was injected 15 min after hPBMCs inoculation and a 60-min dynamic PET scan was acquired, followed by ex-vivo biodistribution studies. Specific uptake was determined by co-injection of tracer with unlabeled IL2 and by evaluating uptake in a control group inoculated with Matrigel only. Results: ⁶⁸Ga-Ga-NODAGA-IL2 and ¹⁸F-AlF-RESCA-IL2 were produced with radiochemical purity >95% and radiochemical yield of 13.1±4.7% and 2.4±1.6% within 60 and 90 min, respectively. Both tracers were stable in serum, with >90% being intact tracer after 1h. In-vitro, both tracers displayed preferential binding to activated hPBMCs. Ex-vivo biodistribution studies in BALB/c mice showed higher uptake of ¹⁸F-AlF-RESCA-IL2 than ¹⁸F-FB-IL2 in liver, kidney, spleen, bone and bone marrow. ⁶⁸Ga-Ga-NODAGA-IL2 uptake in liver and kidney was higher than ¹⁸F-FB-IL2 uptake. In-vivo, all tracers revealed uptake in activated hPBMCs in SCID mice. Low uptake was seen after a blocking dose of IL2 or in the Matrigel control group. In addition, ¹⁸F-AlF-RESCA-IL2 yielded highest contrast PET images of target lymph nodes. Conclusion: Production of ¹⁸F-AlF-RESCA-IL2 and ⁶⁸Ga-Ga-NODAGA-IL2 is simpler and faster than ¹⁸F-FB-IL2. Both tracers showed good in-vitro and in-vivo characteristics with high uptake in lymphoid tissue and hPBMC xenografts.

Purpose: To determine the effect of smooth filter and partial volume correction (PVC) method on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on the molecular imaging (mi) PSMA scoring. Materials & Methods: Men with biochemical recurrence of prostate cancer with negative CT and bone scintigraphy were referred for ¹⁸F-DCFPyL PET/CT. Examinations were performed on one of 2 PET/CT scanners (GE Discovery 610 or Siemens mCT40). All suspected tumor sites were manually contoured on co-registered CT and PET images, and each was assigned a miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomical CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified "rule of thumb" (RoT) correction factor (CF) was derived for lesions at various sizes (<4mm, 4-7mm, 7-9mm, 9-12mm). This was then applied to the original dataset and miPSMA scores obtained using the RoT CF were compared to those found using the actual corrections. Results: There were 75 men (median age, 69 years; median serum PSA of 3.69 ug/L) with 232 metastatic nodes < 12 mm in diameter (mean lesion volume of 313.5 ± 309.6 mm³). Mean SUV_max before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively (p<0.00001). The mean CF for lesions <4mm (n = 22), 4-7mm (n = 140), 7-9mm (n = 50), 9-12 mm (n = 20) was 4 (range: 2.5-6.4), 2.8 (range: 1.6-4.9), 2.3 (range: 1.6-3.3) and 1.8 (range 1.4-2.4), respectively. Overall miPSMA scores were concordant between the corrected dataset and RoT in 205/232 lesions (88.4%). Conclusion: There is a significant effect of smooth filter and partial volume correction on measured PSMA activity in small nodal metastases, impacting the miPSMA score.

Fibroblast activation protein (FAP) has emerged as an interesting molecular target used in the imaging and therapy of various types of cancers. Gallium-68–labeled chelator-linked FAP inhibitors (FAPIs) have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To broaden the spectrum of applicable PET tracers for extended imaging studies of FAP-dependent diseases, we herein report the radiosynthesis and preclinical evaluation of an ¹⁸F–labeled glycosylated FAP inhibitor ([¹⁸F]FGlc-FAPI). Methods: An alkyne-bearing precursor was synthesized and subjected to click chemistry–based radiosynthesis of [¹⁸F]FGlc-FAPI by two-step ¹⁸F-fluoroglycosylation. FAP-expressing HT1080hFAP cells were used to study competitive binding to FAP, cellular uptake, internalization, and efflux of [¹⁸F]FGlc-FAPI in vitro. Biodistribution studies and in vivo small animal PET studies of [¹⁸F]FGlc-FAPI compared to [⁶⁸Ga]Ga-FAPI-04 were conducted in nude mice bearing HT1080hFAP tumors or U87MG xenografts. Results: [¹⁸F]FGlc-FAPI was synthesized with a 15% radioactivity yield and a high radiochemical purity of >99%. In HT1080hFAP cells, [¹⁸F]FGlc-FAPI showed specific uptake, a high internalized fraction, and low cellular efflux. Compared to FAPI-04 (IC50 = 32 nM), the glycoconjugate, FGlc-FAPI (IC50 = 167 nM), showed slightly lower affinity for FAP in vitro, while plasma protein binding was higher for [¹⁸F]FGlc-FAPI. Biodistribution studies revealed significant hepatobiliary excretion of [¹⁸F]FGlc-FAPI; however, small animal PET studies in HT1080hFAP xenografts showed higher specific tumor uptake of [¹⁸F]FGlc-FAPI (4.5 % injected dose per gram of tissue [ID/g]) compared to [⁶⁸Ga]Ga-FAPI-04 (2 %ID/g). In U87MG tumor–bearing mice, both tracers showed similar tumor uptake, but [¹⁸F]FGlc-FAPI showed a higher tumor retention. Interestingly, [¹⁸F]FGlc-FAPI demonstrated high specific uptake in bone structures and joints. Conclusion: [¹⁸F]FGlc-FAPI is an interesting candidate for translation to the clinic, taking advantage of the longer half-life and physical imaging properties of F-18. The availability of [¹⁸F]FGlc-FAPI may allow extended PET studies of FAP-related diseases, such as cancer, but also arthritis, heart diseases, or pulmonary fibrosis.

The value of interim ¹⁸F-fluorodeoxyglucose positron emission tomography (iPET) guided treatment decisions in patients with diffuse large B-cell lymphoma (DLBCL) has been the subject of much debate. This investigation focuses on a comparison of the Deauville score and the deltaSUV_max (SUV_max) approach – two methods to assess early metabolic response to standard chemotherapy in DLBCL. Methods: Of 609 DLBCL patients participating in the Positron Emission Tomography-guided Therapy of Aggressive non-Hodgkin Lymphomas (PETAL) trial, iPET scans of 596 patients originally evaluated using the SUV_max method were available for post-hoc assessment of the Deauville score. A commonly used definition of an unfavorable iPET result according to the Deauville score is an uptake greater than that of the liver, whereas an unfavorable iPET scan with regard to the SUV_max approach is characterized as a relative reduction of the maximum standardized uptake value between baseline and iPET staging of less than or equal to 66%. We investigated the two methods’ correlation and concordance by Spearman’s rank correlation coefficient and the agreement in classification, respectively. We further used Kaplan-Meier curves and Cox regression to assess differences in survival between patient subgroups defined by the pre-specified cut-offs. Time-dependent receiver operating curve analysis provided information on the methods’ respective discrimination performance. Results: Deauville score and SUV_max approach differed in their iPET-based prognosis. The SUV_max approach outperformed the Deauville score in terms of discrimination performance – most likely due to a high number of false-positive decisions by the Deauville score. Cut-off-independent discrimination performance remained low for both methods, but cut-off-related analyses showed promising results. Both favored the SUV_max approach, e.g. for the segregation by iPET response, where the event-free survival hazard ratio was 3.14 (95% confidence interval (CI): 2.22 – 4.46) for SUV_max and 1.70 (95% CI: 1.29 – 2.24) for the Deauville score. Conclusion: When considering treatment intensification, the currently used Deauville score cut-off of an uptake above that of the liver seems to be inappropriate and associated with potential harm for DLBCL patients. The SUV_max criterion of a relative reduction of the maximum standardized uptake value of less than or equal to 66% should be considered as an alternative.

Top-down proteomics studies intact proteoform mixtures and offers important advantages over more common bottom-up proteomics technologies, as it avoids the protein inference problem. However, achieving complete molecular characterization of investigated proteoforms using existing technologies remains a fundamental challenge for top-down proteomics. Here, we benchmark the performance of ultraviolet photodissociation (UVPD) using 213 nm photons generated by a solid-state laser applied to the study of intact proteoforms from three organisms. Notably, the described UVPD setup applies multiple laser pulses to induce ion dissociation, and this feature can be used to optimize the fragmentation outcome based on the molecular weight of the analyzed biomolecule. When applied to complex proteoform mixtures in high-throughput top-down proteomics, 213 nm UVPD demonstrated a high degree of complementarity with the most employed fragmentation method in proteomics studies, higher-energy collisional dissociation (HCD). UVPD at 213 nm offered higher average proteoform sequence coverage and degree of proteoform characterization (including localization of post-translational modifications) than HCD. However, previous studies have shown limitations in applying database search strategies developed for HCD fragmentation to UVPD spectra which contains up to nine fragment ion types. We therefore performed an analysis of the different UVPD product ion type frequencies. From these data, we developed an ad hoc fragment matching strategy and determined the influence of each possible ion type on search outcomes. By paring down the number of ion types considered in high-throughput UVPD searches from all types down to the four most abundant, we were ultimately able to achieve deeper proteome characterization with UVPD. Lastly, our detailed product ion analysis also revealed UVPD cleavage propensities and determined the presence of a product ion produced specifically by 213 nm photons. All together, these observations could be used to better elucidate UVPD dissociation mechanisms and improve the utility of the technique for proteomic applications.

VOLUME 295 (2020) PAGES 4079–4092There was an error in the abstract. “The pyridinium cation hampers uptake of OPs into the central nervous system (CNS)” should read as “The pyridinium cation hampers uptake into the central nervous system (CNS).”

¹⁸F-DCFPyL (2-(3-{1-carboxy-5-[(6-¹⁸F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of ¹⁸F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52–91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), ¹⁸F-fluciclovine PET/CT (18), or ¹⁸F-NaF PET (14). Findings from ¹⁸F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on ¹⁸F-DCFPyL PET/CT was recorded from clinical chart review. Results: ¹⁸F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). ¹⁸F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with ¹⁸F-DCFPyL, whereas ¹⁸F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or ¹⁸F-NaF PET scans were congruent with ¹⁸F-DCFPyL PET, whereas ¹⁸F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or ¹⁸F-NaF PET scans. In 8 of 18 (44%) patients, ¹⁸F-fluciclovine PET had located the same lesions as did ¹⁸F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative ¹⁸F-fluciclovine findings had positive ¹⁸F-DCFPyL PET findings and 1 of 18 (6%) patients with negative ¹⁸F-DCFPyL findings had uptake in the prostate bed on ¹⁸F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, ¹⁸F-DCFPyL and ¹⁸F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after ¹⁸F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on ¹⁸F-DCFPyL PET, despite negative results on conventional imaging. Conclusion: ¹⁸F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration–approved currently available imaging modalities and its impact on clinical management in 60% of patients.

Ingrid Kruse
Apr 1, 2006; 24:91-93
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