Disentangling the influence of entanglement on recruitment in North Atlantic right whales.

North Atlantic right whales are Critically Endangered and declining, with entanglements in fishing gear a key contributor to their decline. Entanglement events can result in lethal and sub-lethal (i.e. increased energetic demands and reduced foraging ability) impacts, with the latter influencing critical life-history states, such as reproduction. Using a multi-event framework, we developed a Bayesian mark-recapture model to investigate the influence of entanglement severity on survival and recruitment for female right whales. We used information from 199 known-aged females sighted between 1977 and 2018, combined with known entanglements of varying severity that were classified as minor, moderate or severe. Severe entanglements resulted in an average decline in survival of 27% for experienced non-breeders, 9% for breeders and 26% for pre-breeding females compared with other entanglements and unentangled individuals. Surviving individuals with severe entanglements had low transitional probabilities to breeders, but surprisingly, individuals with minor entanglements had the lowest transitional probabilities, contrary to expectations underpinning current management actions. Management actions are needed to address the lethal and sub-lethal impacts of entanglements, regardless of severity classification.

Comparison of Predictive Models for Prevention of Missed Endoscopy Appointments- failure of a Predictive Model to Outperform Overbooking Model.

BACKGROUND: Patient late cancelation and nonattendance for endoscopy appointments is an ongoing problem affecting the productivity and wait times of endoscopy units. Previous research evaluated a model for predictive overbooking and had promising results. STUDY: All endoscopy visits at an outpatient endoscopy unit during 4 nonconsecutive months were included in the data analysis. Patients who did not attend their appointment, or canceled with 48 hours of their appointment were considered nonattendees. Demographic, health, and prior visit behavior data was collected and the groups compared. RESULTS: 1780 patients attended 2331 visits in the study period. Comparing the attendee versus non-attendees, there were significant differences in mean age, prior absenteeism, prior cancelations, and total number of hospital visits. No significant differences were seen between groups in winter versus non-winter months, the day of the week, sex distribution, type of procedure booked, or whether the referral was from specialist clinic or direct to procedure. The visit cancelation proportion (calculated excluding current visit) was substantially higher in the absentee group ( P <0.0001). A predictive model was developed and compared to current booking as well as a straight overbooking of 7%. Both overbooking models performed better than the current practice, but the predictive overbooking model did not outperform straight overbooking. CONCLUSIONS: Developing an endoscopy unit specific predictive model may not be more beneficial than straight overbooking as calculated by missed appointment percentage.

Comparative Analysis of Orthosteric and Allosteric GLP-1R Agonists' Effects on Insulin Secretion from Healthy, Diabetic, and Recovered INS-1E Pancreatic Beta Cells.

Despite the availability of different treatments for type 2 diabetes (T2D), post-diagnosis complications remain prevalent; therefore, more effective treatments are desired. Glucagon-like peptide (GLP)-1-based drugs are currently used for T2D treatment. They act as orthosteric agonists for the GLP-1 receptor (GLP-1R). In this study, we analyzed in vitro how the GLP-1R orthosteric and allosteric agonists augment glucose-stimulated insulin secretion (GSIS) and intracellular cAMP production (GSICP) in INS-1E pancreatic beta cells under healthy, diabetic, and recovered states. The findings from this study suggest that allosteric agonists have a longer duration of action than orthosteric agonists. They also suggest that the GLP-1R agonists do not deplete intracellular insulin, indicating they can be a sustainable and safe treatment option for T2D. Importantly, this study demonstrates that the GLP-1R agonists variably augment GSIS through GSICP in healthy, diabetic, and recovered INS-1E cells. Furthermore, we find that INS-1E cells respond differentially to the GLP-1R agonists depending on both glucose concentration during and before treatment and/or whether the cells have been previously exposed to these drugs. In conclusion, the findings described in this manuscript will be useful in determining in vitro how pancreatic beta cells respond to T2D drug treatments in healthy, diabetic, and recovered states.

Comparing First-Year Engineering Student Conceptions of Ethical Decision-Making to Performance on Standardized Assessments of Ethical Reasoning.

The Defining Issues Test 2 (DIT-2) and Engineering Ethical Reasoning Instrument (EERI) are designed to measure ethical reasoning of general (DIT-2) and engineering-student (EERI) populations. These tools-and the DIT-2 especially-have gained wide usage for assessing the ethical reasoning of undergraduate students. This paper reports on a research study in which the ethical reasoning of first-year undergraduate engineering students at multiple universities was assessed with both of these tools. In addition to these two instruments, students were also asked to create personal concept maps of the phrase "ethical decision-making." It was hypothesized that students whose instrument scores reflected more postconventional levels of moral development and more sophisticated ethical reasoning skills would likewise have richer, more detailed concept maps of ethical decision-making, reflecting their deeper levels of understanding of this topic and the complex of related concepts. In fact, there was no significant correlation between the instrument scores and concept map scoring, suggesting that the way first-year students conceptualize ethical decision making does not predict the way they behave when performing scenario-based ethical reasoning (perhaps more situated). This disparity indicates a need to more precisely quantify engineering ethical reasoning and decision making, if we wish to inform assessment outcomes using the results of such quantitative analyses.

The Regulation of Metabolic Homeostasis by Incretins and the Metabolic Hormones Produced by Pancreatic Islets.

In healthy humans, the complex biochemical interplay between organs maintains metabolic homeostasis and pathological alterations in this process result in impaired metabolic homeostasis, causing metabolic diseases such as diabetes and obesity, which are major global healthcare burdens. The great advancements made during the last century in understanding both metabolic disease phenotypes and the regulation of metabolic homeostasis in healthy individuals have yielded new therapeutic options for diseases like type 2 diabetes (T2D). However, it is unlikely that highly desirable more efficacious treatments will be developed for metabolic disorders until the complex systemic regulation of metabolic homeostasis becomes more intricately understood. Hormones produced by pancreatic islet beta-cells (insulin) and alpha-cells (glucagon) are pivotal for maintaining metabolic homeostasis; the activity of insulin and glucagon are reciprocally correlated to achieve strict control of glucose levels (normoglycaemia). Metabolic hormones produced by other pancreatic islet cells and incretins produced by the gut are also crucial for maintaining metabolic homeostasis. Recent studies highlighted the incomplete understanding of metabolic hormonal synergism and, therefore, further elucidation of this will likely lead to more efficacious treatments for diseases such as T2D. The objective of this review is to summarise the systemic actions of the incretins and the metabolic hormones produced by the pancreatic islets and their interactions with their respective receptors.

Experimental and simulation-based characterization of surfactant adsorption layers at fluid interfaces.

Adsorption of surfactants to fluid interfaces occurs in numerous technological and daily-life contexts. The coverage at the interface and other properties of the formed adsorption layers determine the performance of a surfactant with regard to the desired application. Given the importance of these applications, there is a great demand for the comprehensive characterization and understanding of surfactant adsorption layers. In this review, we provide an overview of suitable experimental and simulation-based techniques and review the literature in which they were used for the investigation of surfactant adsorption layers. We come to the conclusion that, while these techniques have been successfully applied to investigate Langmuir monolayers of water-insoluble surfactants, their application to the study of Gibbs adsorption layers of water-soluble surfactants has not been fully exploited. Finally, we emphasize the great potential of these methods in providing a deeper understanding of the behavior of soluble surfactants at interfaces, which is crucial for optimizing their performance in various applications.

Intrafraction displacement of prone versus supine prostate positioning monitored by real-time electromagnetic tracking.

Implanted radiofrequency transponders were used for real-time monitoring of the intrafraction prostate displacement between patients in the prone position and the same patients in the supine position. Thirteen patients had three transponders implanted transperineally and were treated prone with a custom-fitted thermoplastic immobilization device. After collecting data from the last fraction, patients were realigned in the supine position and the displacements of the transponders were monitored for 5-7 minutes. Fourier transforms were applied to the data from each patient to determine periodicity and its amplitude. To remove auto correlation from the stream of displacement data, the distribution of short-term and long-term velocity components were calculated from Poincaré plots of paired sequential vector displacements. The mean absolute displacement was significantly greater prone than supine in the superior-inferior (SI) plane (1.2 ± 0.6 mm vs. 0.6 ± 0.4 mm, p= 0.015), but not for the lateral or anterior-posterior (AP) planes. Displacements were least in the lateral direction. Fourier analyses showed the amplitude of respiratory oscillations was much greater for the SI and AP planes in the prone versus the supine position. Analysis of Poincaré plots confirmed greater short-term variance in the prone position, but no difference in the long-term variance. The centroid of the implanted transponders was offset from the treatment isocenter by > 5 mm for 1.9% of the time versus 0.8% of the time for supine. These results confirmed significantly greater net intrafraction prostate displacement of patients in the prone position than in the supine position, but most of the difference was due to respiration-induced motion that was most pronounced in the SI and AP directions. Because the respiratory motion remained within the action threshold and also within our 5 mm treatment planning margins, there is no compelling reason to choose one treatment position over the other.

Impact of initial biopsy type on the time to final diagnostic biopsy in patients with follicular lymphoma and suspected histologic transformation.

Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively; p=.27), despite more subsequent biopsies performed following initial FNAB. Periprocedural complications were uniformly minimal. Biopsy-proven HT was more common in the initial surgery group and in workups including positron emission tomography/computed tomography (PET/CT). Our findings, derived from US academic centers with specialized procedural and pathology expertise, suggest that FNAB, CNB, and surgical biopsy are all viable initial diagnostic procedures that can inform clinical decision-making in select FL patients with suspected HT.

Air-kerma strength determination of a new directional (103)Pd source.

PURPOSE: A new directional (103)Pd planar source array called a CivaSheet™ has been developed by CivaTech Oncology, Inc., for potential use in low-dose-rate (LDR) brachytherapy treatments. The array consists of multiple individual polymer capsules called CivaDots, containing (103)Pd and a gold shield that attenuates the radiation on one side, thus defining a hot and cold side. This novel source requires new methods to establish a source strength metric. The presence of gold material in such close proximity to the active (103)Pd region causes the source spectrum to be significantly different than the energy spectra of seeds normally used in LDR brachytherapy treatments. In this investigation, the authors perform air-kerma strength (S(K)) measurements, develop new correction factors for these measurements based on an experimentally verified energy spectrum, and test the robustness of transferring S(K) to a well-type ionization chamber. METHODS: S(K) measurements were performed with the variable-aperture free-air chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center. Subsequent measurements were then performed in a well-type ionization chamber. To realize the quantity S(K) from a directional source with gold material present, new methods and correction factors were considered. Updated correction factors were calculated using the MCNP 6 Monte Carlo code in order to determine S(K) with the presence of gold fluorescent energy lines. In addition to S(K) measurements, a low-energy high-purity germanium (HPGe) detector was used to experimentally verify the calculated spectrum, a sodium iodide (NaI) scintillating counter was used to verify the azimuthal and polar anisotropy, and a well-type ionization chamber was used to test the feasibility of disseminating S(K) values for a directional source within a cylindrically symmetric measurement volume. RESULTS: The UW VAFAC was successfully used to measure the S(K) of four CivaDots with reproducibilities within 0.3%. Monte Carlo methods were used to calculate the UW VAFAC correction factors and the calculated spectrum emitted from a CivaDot was experimentally verified with HPGe detector measurements. The well-type ionization chamber showed minimal variation in response (<1.5%) as a function of source positioning angle, indicating that an American Association of Physicists in Medicine (AAPM) Accredited Dosimetry Calibration Laboratory calibrated well chamber would be a suitable device to transfer an S(K)-based calibration to a clinical user. S(K) per well-chamber ionization current ratios were consistent among the four dots measured. Additionally, the measurements and predictions of anisotropy show uniform emission within the solid angle of the VAFAC, which demonstrates the robustness of the S(K) measurement approach. CONCLUSIONS: This characterization of a new (103)Pd directional brachytherapy source helps to establish calibration methods that could ultimately be used in the well-established AAPM Task Group 43 formalism. Monte Carlo methods accurately predict the changes in the energy spectrum caused by the fluorescent x-rays produced in the gold shield.

103Pd strings: Monte Carlo assessment of a new approach to brachytherapy source design.

PURPOSE: A new type of (103)Pd source (CivaString and CivaThin by CivaTech Oncology, Inc.) is examined. The source contains (103)Pd and Au radio-opaque marker(s), all contained within low-Zeff organic polymers that permit source flexibility. The CivaString source is available in lengths L of 10, 20, 30, 40, 50, and 60 mm, and referred to in the current study as CS10-CS60, respectively. A thinner design, CivaThin, has sources designated as CT10-CT60, respectively. The CivaString and CivaThin sources are 0.85 and 0.60 mm in diameter, respectively. The source design is novel and offers an opportunity to examine its interesting dosimetric properties in comparison to conventional (103)Pd seeds. METHODS: The MCNP5 radiation transport code was used to estimate air-kerma rate and dose rate distributions with polar and cylindrical coordinate systems. Doses in water and prostate tissue phantoms were compared to determine differences between the TG-43 formalism and realistic clinical circumstances. The influence of Ti encapsulation and 2.7 keV photons was examined. The accuracy of superposition of dose distributions from shorter sources to create longer source dose distributions was also assessed. RESULTS: The normalized air-kerma rate was not highly dependent on L or the polar angle θ, with results being nearly identical between the CivaString and CivaThin sources for common L. The air-kerma strength was also weakly dependent on L. The uncertainty analysis established a standard uncertainty of 1.3% for the dose-rate constant Λ, where the largest contributors were µen/ρ and µ/ρ. The Λ values decreased with increasing L, which was largely explained by differences in solid angle. The radial dose function did not substantially vary among the CivaString and CivaThin sources for r ≥ 1 cm. However, behavior for r < 1 cm indicated that the Au marker(s) shielded radiation for the sources having L = 10, 30, and 50 mm. The 2D anisotropy function exhibited peaks and valleys that corresponded to positions adjacent to (103)Pd wells and Au markers, respectively. Dose distributions of both source types had minimal anisotropy in comparison to conventional (103)Pd seeds. Contributions by 2.7 keV photons comprised ≤ 0.1% of the dose from all photons at positions farther than 0.13 mm from the polymer source surface. Differences between absorbed dose to water and prostate became more substantial as distance from the sources increased, with prostate dose being about 13% lower for r = 5 cm. Using a cylindrical coordinate system, dose superposition of small length sources to replicate the dose distribution for a long length source proved to be a robust technique; a 2.0% tolerance compared with the reference dose distribution did not exceed 0.1 cm(3) for any of the examined source combinations. CONCLUSIONS: By design, the CivaString and CivaThin sources have novel dosimetric characteristics in comparison to Ti-encapsulated (103)Pd seeds. The dosimetric characterization has determined the reasons for these differences through analysis using Monte Carlo-based radiation transport simulations.

Experimental and Monte Carlo dosimetric characterization of a 1 cm (103)Pd brachytherapy source.

PURPOSE: To determine the in-air azimuthal anisotropy and in-water dose distribution for the 1 cm length of a new elongated (103)Pd brachytherapy source through both experimental measurements and Monte Carlo (MC) simulations. Measured and MC-calculated dose distributions were used to determine the American Association of Physicists in Medicine Task Group No. 43 (TG-43) dosimetry parameters for this source. METHODS AND MATERIALS: The in-air azimuthal anisotropy of the source was measured with a NaI scintillation detector and was simulated with the MCNP5 radiation transport code. Measured and MC results were normalized to their respective mean values and then compared. The source dose distribution was determined from measurements with LiF:Mg,Ti thermoluminescent dosimeter (TLD) microcubes and MC simulations. TG-43 dosimetry parameters for the source, including the dose-rate constant, Λ, two-dimensional anisotropy function, F(r, θ), and line-source radial dose function, gL(r), were determined from the TLD measurements and MC simulations. RESULTS: NaI scintillation detector measurements and MC simulations of the in-air azimuthal anisotropy of the source showed that ≥95% of the normalized values for each source were within 1.2% of the mean value. TLD measurements and MC simulations of Λ, F(r, θ), and gL(r) agreed to within the associated uncertainties. CONCLUSIONS: This new (103)Pd source exhibits a high level of azimuthal symmetry as indicated by the measured and MC-calculated results for the in-air azimuthal anisotropy. TG-43 dosimetry parameters for the source were determined through TLD measurements and MC simulations.

Electromagnetic transponders indicate prostate size increase followed by decrease during the course of external beam radiation therapy.

PURPOSE: Real-time image guidance enables more accurate radiation therapy by tracking target movement. This study used transponder positions to monitor changes in prostate volume that may be a source of dosimetric and target inaccuracy. METHODS AND MATERIALS: Twenty-four men with biopsy-proven T1c-T3a prostate cancer each had three electromagnetic transponders implanted transperineally. Their coordinates were recorded by the Calypso system, and the perimeter of the triangle formed by the transponders was used to calculate prostate volumes at sequential time points throughout the course of radiation therapy to a dose of 81 Gy in 1.8-Gy fractions. RESULTS: There was a significant decrease in mean prostate volume of 10.9% from the first to the final day of radiation therapy. The volume loss did not occur monotonically but increased in most patients (75%) during the first several weeks to a median maximum on Day 7. The volume increased by a mean of 6.1% before decreasing by a mean maximum difference of 18.4% to nadir (p < 0.001 for both increase and decrease). Glandular shrinkage was asymmetric, with the apex to right base dimension varying more than twice that of the lateral dimension. For all dimensions, the mean change was <0.5 cm. CONCLUSION: Real-time transponder positions indicated a volume increase during the initial days of radiation therapy and then significant and asymmetric shrinkage by the final day. Understanding and tracking volume fluctuations of the prostate during radiation therapy can help real-time imaging technology perform to its fullest potential.

Postimplant rectal dosimetry is not dependent on 103Pd or 125I seed activity.

PURPOSE: In this study, the effect of prostate brachytherapy seed activity on postimplant rectal dosimetry was evaluated in Pro-Qura (Prostate Brachytherapy Quality Assurance; Seattle, WA) proctored, community-based programs. METHODS AND MATERIALS: Twenty-three hundred patients (1563 iodine-125 [(125)I] and 737 palladium-103 [(103)Pd]) from 78 brachytherapists with postimplant rectal dosimetry were identified. Seed activity was stratified into three tertiles for each isotope (≤0.300, 0.301-0.326, and >0.326 mCi/seed for (125)I and ≤1.330, 1.331-1.547, and >1.547 mCi/seed for (103)Pd). Postimplant dosimetry was performed in a standardized fashion. The rectum was contoured by outlining the outer rectal wall. The volume of the rectum receiving 100% of the prescription dose (R(100)) was calculated in cubic centimeters. The prostate V(100) and D(90) volumes were also calculated. RESULTS: The mean prostate volume was 35.8 and 32.3 cm(3) for (125)I and (103)Pd. The median time to postimplant CT was 30 days. For (125)I, the V(100) increased from 91.0% to 93.7% (p=0.012) and the D(90) increased from 105.9% to 108.7% (p<0.001) for the lowest to the highest (125)I seed activities. In contrast, no significant changes in V(100) (p=0.751) or D(90) (p=0.200) were discerned when stratified by seed activity. For both isotopes, there was no correlation between seed activity and R(100), and R(100) was highest for the intermediate seed activities. Overall, the R(100) was lower for (103)Pd vs. (125)I (0.63 vs. 0.82 cm(3), p<0.001). CONCLUSIONS: Within the confines of seed activities used in this study, higher activity seeds did not result in a deleterious effect on rectal dose. Higher activity seeds were associated with improved prostate dosimetry for (125)I, whereas (103)Pd dosimetry was not dependent on seed activity.

High-risk prostate cancer with Gleason score 8-10 and PSA level ≤15 ng/mL treated with permanent interstitial brachytherapy.

PURPOSE: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) ≥8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS ≥8 and a PSA level ≤15 ng/mL with or without androgen-deprivation therapy (ADT). METHODS AND MATERIALS: From April 1995 to October 2005, 174 patients with GS ≥8 and a PSA level ≤15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level ≤0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. RESULTS: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. CONCLUSIONS: Patients with GS ≥8 and PSA level ≤15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

Electromagnetic tracking of intrafraction prostate displacement in patients externally immobilized in the prone position.

PURPOSE: To evaluate intrafraction prostate displacement among patients immobilized in the prone position using real-time monitoring of implanted radiofrequency transponders. METHODS AND MATERIALS: The Calypso localization system was used to track prostate motion in patients receiving external beam radiation therapy (XRT) for prostate cancer. All patients were treated in the prone position and immobilized with a thermoplastic immobilization device. Real-time measurement of prostate displacement was recorded for each treatment fraction. These measurements were used to determine the duration and magnitude of displacement along the three directional axes. RESULTS: The calculated centroid of the implanted transponders was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 38.0%, 13.9%, and 4.5% of the time. In the lateral dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 2.7%, 0.4%, and 0.06% of the time. In the superior-inferior dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 16.1%, 4.7%, and 1.5% of the time, respectively. In the anterior-posterior dimension, the centroid was offset from the treatment isocenter by >or=2 mm, >or=3 mm, and >or=4 mm for 13.4%, 3.0%, and 0.5% of the time. CONCLUSIONS: Intrafraction prostate displacement in the prone position is comparable to that in the supine position. For patients with large girth, in whom the supine position may preclude accurate detection of implanted radiofrequency transponders, treatment in the prone position is a suitable alternative.

Permanent prostate brachytherapy in prostate glands <20 cm(3).

PURPOSE: To investigate the dosimetry, treatment-related morbidity, and biochemical outcomes for brachytherapy in patients with prostate glands <20 cm(3). METHODS AND MATERIALS: From November 1996 to October 2006, 104 patients with prostate glands <20 cm(3) underwent brachytherapy. Multiple prostate, urethral, and rectal dosimetric parameters were evaluated. Treatment-related urinary and rectal morbidity were assessed from patient questionnaires. Cause-specific survival, biochemical progression-free survival, and overall survival were recorded. RESULTS: The median patient age, follow up, and pre-treatment ultrasound volume was 64 years, 5.0 years and 17.6cm(3), respectively. Median day 0 dosimetry was significant for the following: V100 98.5%, D90 126.1% and R100 <0.5% of prescription dose. The mean urethral and maximum urethral doses were 119.6% and 133.8% of prescription. The median time to International Prostate Symptom Score resolution was 4 months. There were no RTOG grade III or IV rectal complications. The cause-specific survival, biochemical progression-free survival, and overall survival rates were 100%, 92.5%, and 77.8% at 9 years. For biochemically disease-free patients, the median most recent postbrachytherapy PSA value was 0.02 ng/mL. CONCLUSION: Our results demonstrate that brachytherapy for small prostate glands is highly effective, with an acceptable morbidity profile, excellent postimplant dosimetry, acceptable treatment-related morbidity, and favorable biochemical outcomes.