Dosimetric characterization of a new surface-conforming electron MLC prototype.

The purpose is to reduce normal tissue radiation toxicity for electron therapy through the creation of a surface-conforming electron multileaf collimator (SCEM). The SCEM combines the benefits of skin collimation, electron conformal radiotherapy, and modulated electron radiotherapy. An early concept for the SCEM was constructed. It consists of leaves that protrude towards the patient, allowing the leaves to conform closely to irregular patient surfaces. The leaves are made of acrylic to decrease bremsstrahlung, thereby decreasing the out-of-field dose. Water tank scans were performed with the SCEM in place for various field sizes for all available electron energies (6, 9, 12, and 15 MeV) with a 0.5 cm air gap to the water surface at 100 cm source-to-surface distance (SSD). These measurements were compared with Cerrobend cutouts with the field size-matched at 100 and 110 cm SSD. Output factor measurements were taken in solid water for each energy at dmax for both the cerrobend cutouts and SCEM at 100 cm SSD. Percent depth dose (PDD) curves for the SCEM shifted shallower for all energies and field sizes. The SCEM also produced a higher surface dose relative to Cerrobend cutouts, with the maximum being a 9.8% increase for the 3 cm × 9 cm field at 9 MeV. When compared to the Cerrobend cutouts at 110 cm SSD, the SCEM showed a significant decrease in the penumbra, particularly for lower energies (i.e., 6 and 9 MeV). The SCEM also showed reduced out-of-field dose and lower bremsstrahlung production than the Cerrobend cutouts. The SCEM provides significant improvement in the penumbra and out-of-field dose by allowing collimation close to the skin surface compared to Cerrobend cutouts. However, the added scatter from the SCEM increases shallow PDD values. Future work will focus on reducing this scatter while maintaining the penumbra and out-of-field benefits the SCEM has over conventional collimation.

Hydrogen sulfide decreases photodynamic therapy outcome through the modulation of the cellular redox state.

Photodynamic therapy (PDT) is a non-surgical treatment that has been approved for its human medical use in many cancers. PDT involves the interaction of a photosensitizer (PS) with light. The amino acid 5- aminolevulinic acid (ALA) can be used as a pro-PS, leading to the synthesis of Protoporphyrin IX. Hydrogen sulfide (H2S) is an endogenously produced gas that belongs to the gasotransmitter family, which can diffuse through biological membranes and have relevant physiological effects such as cardiovascular functions, vasodilatation, inflammation, cell cycle and neuro-modulation. It was also proposed to have cytoprotective effects. We aimed to study the modulatory effects of H2S on ALAPDT in the mammary adenocarcinoma cell line LM2. Exposure of the cells to NaHS (donor of H2S) in concentrations up to 10 mM impaired the response to ALA-PDT in a dose-dependent manner. The addition of 3 doses of NaHS showed the highest effect. This decreased response to the photodynamic treatment was correlated to an increase in the GSH levels, catalase activity, a dose dependent reduction of PpIX and increased intracellular ALA, decreased levels of oxidized proteins and a decrease of PDT-induced ROS. NaHS also reduced the levels of singlet oxygen in an in vitro assay. H2S also protected other cells of different origins against PDT mediated by ALA and other PSs. These results suggest that H2S has a role in the modulation of the redox state of the cells, and thus impairs the response to ALA-PDT through multifactor pathways. These findings could contribute to developing new strategies to improve the effectiveness of PDT particularly mediated by ALA or other ROS-related treatments.

End to end comparison of surface-guided imaging versus stereoscopic X-rays for the SRS treatment of multiple metastases with a single isocenter using 3D anthropomorphic gel phantoms.

INTRODUCTION: Two end-to-end tests evaluate the accuracy of a surface-guided radiation therapy (SGRT) system (CRAD Catalyst HD) for position verification in comparison to a stereoscopic x-ray imaging system (Brainlab Exactrac ) for single-isocenter, multiple metastases stereotactic radiosurgery (SRS) using 3D polymer gel inserts. MATERIALS AND METHODS: A 3D-printed phantom (Prime phantom, RTsafe PC, Athens, Greece) with two separate cylindrical polymer gel inserts were immobilized in open-face masks and treated with a single isocentric, multitarget SRS plan. Planning was done in Brainlab (Elements) to treat five metastatic lesions in one fraction, and initial setup was done using cone beam computed tomography. Positional verification was done using orthogonal X-ray imaging (Brainlab Exactrac) and/or a surface imaging system (CRAD Catalyst HD, Uppsala, Sweden), and shift discrepancies were recorded for each couch angle. Forty-two hours after irradiation, the gel phantom was scanned in a 1.5 Tesla MRI, and images were fused with the patient computed tomography data/structure set for further analysis of spatial dose distribution. RESULTS: Discrepancies between the CRAD Catalyst HD system and Brainlab Exactrac were <1 mm in the translational direction and <0.5° in the angular direction at noncoplanar couch angles. Dose parameters (DMean% , D95% ) and 3D gamma index passing rates were evaluated for both setup modalities for each planned target volume (PTV) at a variety of thresholds: 3%/2 mm (Exactrac≥93.1% and CRAD ≥87.2%), 5%/2 mm (Exactrac≥95.6% and CRAD ≥94.6%), and 5%/1 mm (Exactrac≥81.8% and CRAD ≥83.7%). CONCLUSION: Dose metrics for a setup with surface imaging was found to be consistent with setup using x-ray imaging, demonstrating high accuracy and reproducibility for treatment delivery. Results indicate the feasibility of using surface imaging for position verification at noncoplanar couch angles for single-isocenter, multiple-target SRS using end-to-end quality assurance (QA) testing with 3D polymer gel dosimetry.

Interprofessional communication in medical simulation: findings from a scoping review and implications for academic medicine.

BACKGROUND: Interprofessional communication is fundamental to the delivery of healthcare and can be taught in medical school and other health professional schools through interprofessional education (IPE) activities. Simulation centers have become a predominant location for simulation IPE activities with infrastructure able to support high fidelity activities in a controlled environment. In this secondary analysis of a scoping review conducted on simulation-based IPE, we describe the characteristics of previously reported simulation IPE activities involving undergraduate medical students in a simulation center focused on interprofessional communication. METHODS: Electronic searches of PubMed, CINAHL, and ERIC databases in accordance with PRISMA-ScR guidelines were conducted to isolate relevant articles from 2016-2020. In total, 165 peer-reviewed articles met inclusion criteria and data extraction linked to four research questions was applied by one individual and the accuracy was confirmed by a second individual. A secondary analysis was performed to describe what existing approaches for simulation IPE in simulation center settings have been used to explicitly achieve interprofessional communication competencies in undergraduate medical education. A sub-dataset was developed from the original scoping review and identified 21 studies describing simulation IPE activities that took place in dedicated simulation centers, targeted the IPEC interprofessional communication domain, and involved undergraduate medical students. RESULTS: Though diverse, the majority of simulation IPE activities described high-fidelity approaches involving standardized patients and utilized assessment tools with established validity evidence in IPE activities to measure learning outcomes. A minority of simulation IPE activities were described as hybrid and utilized more than one resource or equipment for the activity and only two were longitudinal in nature. Learning outcomes were focused predominantly on modification of attitudes/perceptions and few targeted higher levels of assessment. CONCLUSIONS: Educators charged with developing simulation IPE activities for medical students focused on interprofessional communication should incorporate assessment tools that have validity evidence from similar activities, target higher level learning outcomes, and leverage hybrid models to develop longitudinal simulation IPE activities. Though an ideal environment to achieve higher level learning outcomes, simulation centers are not required for meaningful simulation IPE activities.

Novel meso-substituted porphyrin derivatives and its potential use in photodynamic therapy of cancer.

BACKGROUND: Photodynamic therapy (PDT) is an anticancer treatment that utilizes the interaction of light and a photosensitiser (PS), promoting tumour cell death mediated by generation of reactive oxygen species. In this study, we evaluated the in vitro photoactivity of four meso-substituted porphyrins and a porphyrin coupled to a fullerene. METHODS: The cell line employed was the LM3 mammary adenocarcinoma, and the PS with the best photokilling activity was administered to mice bearing the LM3 subcutaneously implanted adenocarcinoma. The TEMCP4+ porphyrin and its analogue TEMCC4+ chlorine contain four identical carbazoyl substituents at the meso positions of the tetrapyrrolic macrocycle and have A4 symmetry. The TAPP derivative also has A4 symmetry, and it is substituted at the meso positions by aminopropoxy groups. The DAPP molecule has ABAB symmetry with aminopropoxy and the trifluoromethyl substituents in trans positions. The TCP-C604+ dyad is formed by a porphyrin unit covalently attached to the fullerene C60. RESULTS: The PSs are taken up by the cells with the following efficiency: TAPP> TEMCP4+ = TEMCC4+ > DAPP >TCP-C604+, and the amount of intracellular PS correlates fairly with the photodamage degree, but also the quantum yields of singlet oxygen influence the PDT outcome. TAPP, DAPP, TEMCC4+ and TEMCP4+ exhibit high photoactivity against LM3 mammary carcinoma cells, being TAPP the most active. After topical application of TAPP on the skin of mice bearing LM3 tumours, the molecule is localized mainly in the stratum corneum, and at a lower extent in hair follicles and sebaceous glands. Systemic administration of TAPP produces a tumour: normal skin ratio of 31.4, and high accumulation in intestine and lung. CONCLUSION: The results suggest a potential use of topical TAPP for the treatment of actinic keratosis and skin adnexal neoplasms. In addition, selectivity for tumour tissue after systemic administration highlights the selectivity of and potentiality of TAPP as a new PS.

Apoptotic cell death induced by dendritic derivatives of aminolevulinic acid in endothelial and foam cells co-cultures.

Photodynamic therapy (PDT) is an effective procedure for the treatment of lesions diseases based on the selectivity of a photosensitising compound with the ability to accumulate in the target cell. Atherosclerotic plaque is a suitable target for PDT because of the preferential accumulation of photosensitisers in atherosclerotic plaques. Dendrimers are hyperbranched polymers conjugated to drugs. The dendrimers of ALA hold ester bonds that inside the cells are cleaved and release ALA, yielding PpIX production. The dendrimer 6m-ALA was chosen to perform this study since in previous studies it induced the highest porphyrin macrophage: endothelial cell ratio (Rodriguez et al. in Photochem Photobiol Sci 14:1617-1627, 2015). We transformed Raw 264.7 macrophages to foam cells by exposure to oxidised LDLs, and we employed a co-culture model of HMEC-1 endothelial cells and foam cells to study the affinity of ALA dendrimers for the foam cells. In this work it was proposed an in vitro model of atheromatous plaque, the aim was to study the selectivity of an ALA dendrimer for the foam cells as compared to the endothelial cells in a co-culture system and the type of cell death triggered by the photodynamic treatment. The ALA dendrimer 6m-ALA showed selectivity PDT response for foam cells against endothelial cells. A light dose of 1 J/cm2 eliminate foam cells, whereas less than 50% of HMEC-1 is killed, and apoptosis cell death is involved in this process, and no necrosis is present. We propose the use of ALA dendrimers as pro-photosensitisers to be employed in photoangioplasty to aid in the treatment of obstructive cardiovascular diseases, and these molecules can also be employed as a theranostic agent.

On the evaluation of mobile target trajectory between four-dimensional computer tomography and four-dimensional cone-beam computer tomography.

PURPOSE: For mobile lung tumors, four-dimensional computer tomography (4D CT) is often used for simulation and treatment planning. Localization accuracy remains a challenge in lung stereotactic body radiation therapy (SBRT) treatments. An attractive image guidance method to increase localization accuracy is 4D cone-beam CT (CBCT) as it allows for visualization of tumor motion with reduced motion artifacts. However, acquisition and reconstruction of 4D CBCT differ from that of 4D CT. This study evaluates the discrepancies between the reconstructed motion of 4D CBCT and 4D CT imaging over a wide range of sine target motion parameters and patient waveforms. METHODS: A thorax motion phantom was used to examine 24 sine motions with varying amplitudes and cycle times and seven patient waveforms. Each programmed motion was imaged using 4D CT and 4D CBCT. The images were processed to auto segment the target. For sine motion, the target centroid at each phase was fitted to a sinusoidal curve to evaluate equivalence in amplitude between the two imaging modalities. The patient waveform motion was evaluated based on the average 4D data sets. RESULTS: The mean difference and root-mean-square-error between the two modalities for sine motion were -0.35 ± 0.22 and 0.60 mm, respectively, with 4D CBCT slightly overestimating amplitude compared with 4D CT. The two imaging methods were determined to be significantly equivalent within ±1 mm based on two one-sided t tests (p < 0.001). For patient-specific motion, the mean difference was 1.5 ± 2.1 (0.8 ± 0.6 without outlier), 0.4 ± 0.3, and 0.8 ± 0.6 mm for superior/inferior (SI), anterior/posterior (AP), and left/right (LR), respectively. CONCLUSION: In cases where 4D CT is used to image mobile tumors, 4D CBCT is an attractive localization method due to its assessment of motion with respect to 4D CT, particularly for lung SBRT treatments where accuracy is paramount.

Quantifying false positional corrections due to facial motion using SGRT with open-face Masks.

PURPOSE: Studies have evaluated the viability of using open-face masks as an immobilization technique to treat intracranial and head and neck cancers. This method offers less stress to the patient with comparable accuracy to closed-face masks. Open-face masks permit implementation of surface guided radiation therapy (SGRT) to assist in positioning and motion management. Research suggests that changes in patient facial expressions may influence the SGRT system to generate false positional corrections. This study aims to quantify these errors produced by the SGRT system due to face motion. METHODS: Ten human subjects were immobilized using open-face masks. Four discrete SGRT regions of interest (ROIs) were analyzed based on anatomical features to simulate different mask openings. The largest ROI was lateral to the cheeks, superior to the eyebrows, and inferior to the mouth. The smallest ROI included only the eyes and bridge of the nose. Subjects were asked to open and close their eyes and simulate fear and annoyance and peak isocenter shifts were recorded. This was performed in both standard and SRS specific resolutions with the C-RAD Catalyst HD system. RESULTS: All four ROIs analyzed in SRS and Standard resolutions demonstrated an average deviation of 0.3 ± 0.3 mm for eyes closed and 0.4 ± 0.4 mm shift for eyes open, and 0.3 ± 0.3 mm for eyes closed and 0.8 ± 0.9 mm shift for eyes open. The average deviation observed due to changing facial expressions was 1.4 ± 0.9 mm for SRS specific and 1.6 ± 1.6 mm for standard resolution. CONCLUSION: The SGRT system can generate false positional corrections for face motion and this is amplified at lower resolutions and smaller ROIs. These errors should be considered in the overall tolerances and treatment plan when using open-face masks with SGRT and may warrant additional radiographic imaging.

A customizable aluminum compensator system for total body irradiation.

PURPOSE: To develop a simplified aluminum compensator system for total body irradiation (TBI) that is easy to assemble and modify in a short period of time for customized patient treatments. METHODS: The compensator is composed of a combination of 0.3 cm thick aluminum bars, two aluminum T-tracks, spacers, and metal bolts. The system is mounted onto a plexiglass block tray. The design consists of 11 fixed sectors spanning from the patient's head to feet. The outermost sectors utilize 7.6 cm wide aluminum bars, while the remaining sectors use 2.5 cm wide aluminum bars. There is a magnification factor of 5 from the compensator to the patient treatment plane. Each bar of aluminum is interconnected at each adjacent sector with a tongue and groove arrangement and fastened to the T-track using a metal washer, bolt, and nut. Inter-bar leakage of the compensator was tested using a water tank and diode. End-to-end measurements were performed with an ion chamber in a solid water phantom and also with a RANDO phantom using internal and external optically stimulated luminescent detectors (OSLDs). In-vivo patient measurements from the first 20 patients treated with this aluminum compensator were compared to those from 20 patients treated with our previously used lead compensator system. RESULTS: The compensator assembly time was reduced to 20-30 min compared to the 2-4 h it would take with the previous lead design. All end-to-end measurements were within 10% of that expected. The median absolute in-vivo error for the aluminum compensator was 3.7%, with 93.8% of measurements being within 10% of that expected. The median error for the lead compensator system was 5.3%, with 85.1% being within 10% of that expected. CONCLUSION: This design has become the standard compensator at our clinic. It allows for quick assembly and customization along with meeting the Task Group 29 recommendations for dose uniformity.

Dual Antiplatelet Therapy Is Associated With Coagulopathy Detectable by Thrombelastography in Acute Stroke.

BACKGROUND: Thrombelastography (TEG) provides a global, dynamic measure of coagulation. We examined the effect of antiplatelet (AP) medications on coagulation in patients with acute stroke as measured by TEG. METHODS: We reviewed prospectively collected data on patients presenting with acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH) between 2009 and 2014. Patient demographics and baseline TEG values were compared among 4 different drug use groups: aspirin only, clopidogrel only, both aspirin and clopidogrel, and no AP. Multivariable regression models were conducted to compare the differences in TEG components. RESULTS: A total of 202 patients were included, 139 with AIS and 63 with ICH. Forty-eight (24%) patients were taking aspirin alone, 12 (6%) were taking clopidogrel, 16 (8%) dual AP, and 126 (62%) no AP. Dual AP use was associated with prolonged mean R (time to initiate clotting) of 5.5 minutes as compared to no AP use (4.6 minutes, P = .04). Additionally, mean maximal amplitude (MA; final clot strength) and angle (rate of clot formation) were decreased in the dual AP group (MA = 59.3 mm, angle = 57.8°) as compared to the no AP group (MA = 64.5 mm, angle = 64.5°; P = .04 and P = .01, respectively). Patients on single AP therapy (either aspirin or clopidogrel) did not differ from those on no AP therapy in any TEG parameters measured. CONCLUSION: Dual AP therapy is associated with a detectable coagulopathy which may have implications in the management of patients with AIS and hemorrhagic stroke. The effects of single AP therapy may not be demonstrated by TEG.

Deep learning-based survival analysis for brain metastasis patients with the national cancer database.

PURPOSE: Prognostic indices such as the Brain Metastasis Graded Prognostic Assessment have been used in clinical settings to aid physicians and patients in determining an appropriate treatment regimen. These indices are derivative of traditional survival analysis techniques such as Cox proportional hazards (CPH) and recursive partitioning analysis (RPA). Previous studies have shown that by evaluating CPH risk with a nonlinear deep neural network, DeepSurv, patient survival can be modeled more accurately. In this work, we apply DeepSurv to a test case: breast cancer patients with brain metastases who have received stereotactic radiosurgery. METHODS: Survival times, censorship status, and 27 covariates including age, staging information, and hormone receptor status were provided for 1673 patients by the NCDB. Monte Carlo cross-validation with 50 samples of 1400 patients was used to train and validate the DeepSurv, CPH, and RPA models independently. DeepSurv was implemented with L2 regularization, batch normalization, dropout, Nesterov momentum, and learning rate decay. RPA was implemented as a random survival forest (RSF). Concordance indices of test sets of 140 patients were used for each sample to assess the generalizable predictive capacity of each model. RESULTS: Following hyperparameter tuning, DeepSurv was trained at 32 min per sample on a 1.33 GHz quad-core CPU. Test set concordance indices of 0.7488 ± 0.0049, 0.6251 ± 0.0047, and 0.7368 ± 0.0047, were found for DeepSurv, CPH, and RSF, respectively. A Tukey HSD test demonstrates a statistically significant difference between the mean concordance indices of the three models. CONCLUSION: Our results suggest that deep learning-based survival prediction can outperform traditional models, specifically in a case where an accurate prognosis is highly clinically relevant. We recommend that where appropriate data are available, deep learning-based prognostic indicators should be used to supplement classical statistics.

An open-source tool to visualize potential cone collisions while planning SRS cases.

PURPOSE: To create an open-source visualization program that allows one to find potential cone collisions while planning intracranial stereotactic radiosurgery cases. METHODS: Measurements of physical components in the treatment room (gantry, cone, table, localization stereotactic radiation surgery frame, etc.) were incorporated into a script in MATLAB (MathWorks, Natick, MA) that produces three-dimensional visualizations of the components. A localization frame, used during simulation, fully contains the patient. This frame was used to represent a safety zone for collisions. Simple geometric objects are used to approximate the simulated components. The couch is represented as boxes, the gantry head and cone are represented by cylinders, and the patient safety zone can be represented by either a box or ellipsoid. These objects are translated and rotated based upon the beam geometry and the treatment isocenter to mimic treatment. A simple graphical user interface (GUI) was made in MATLAB (compatible with GNU Octave) to allow users to pass the treatment isocenter location, the initial and terminal gantry angles, the couch angle, and the number of angular points to visualize between the initial and terminal gantry angle. RESULTS: The GUI provides a fast and simple way to discover collisions in the treatment room before the treatment plan is completed. Twenty patient arcs were used as an end-to-end validation of the system. Seventeen of these appeared the same in the software as in the room. Three of the arcs appeared closer in the software than in the room. This is due to the treatment couch having rounded corners, whereas the software visualizes sharp corners. CONCLUSIONS: This simple GUI can be used to find the best orientation of beams for each patient. By finding collisions before a plan is being simulated in the treatment room, a user can save time due to replanning of cases.

Patient-specific dose quality assurance of single-isocenter multiple brain metastasis stereotactic radiosurgery using PTW Octavius 4D.

PURPOSE: Single-isocenter multiple brain metastasis stereotactic radiosurgery is an efficient treatment modality increasing in clinical practice. The need to provide accurate, patient-specific quality assurance (QA) for these plans is met by several options. This study reviews some of these options and explores the use of the Octavius 4D as a solution for patient-specific plan quality assurance. METHODS: The Octavius 4D Modular Phantom (O4D) with the 1000 SRS array was evaluated in this study. The array consists of 977 liquid-filled ion chambers. The center 5.5 cm × 5.5 cm area has a detector spacing of 2.5 mm. The ability of the O4D to reconstruct three-dimensional (3D) dose was validated against a 3D gel dosimeter, ion chamber, and film measurements. After validation, 15 patients with 2-11 targets had their plans delivered to the phantom. The criteria used for the gamma calculation was 3%/1 mm. The portion of targets which were measurable by the phantom was countable. The accompanying software compiled the measured doses allowing each target to be counted from the measured dose distribution. RESULTS: Spatial resolution was sufficient to verify the high dose distributions characteristic of SRS. Amongst the 15 patients there were 74 targets. Of the 74 targets, 61 (82%) of them were visible on the measured dose distribution. The average gamma passing rate was 99.3% (with sample standard deviation of 0.68%). CONCLUSIONS: The high resolution provided by the O4D with 1000 SRS board insert allows for very high-resolution measurement. This high resolution in turn can allow for high gamma passing rates. The O4D with the 1000 SRS array is an acceptable method of performing quality assurance for single-isocenter multiple brain metastasis SRS.

A dosimetric analysis of a spine SBRT specific treatment planning system.

PURPOSE: The Brainlab Elements treatment planning system utilizes distinct modules for treatment planning specific to stereotactic treatment sites including single or multiple brain lesions as well as spine. This work investigates the hypothesis that an optimization tailored specifically to spine can in fact create dosimetrically superior plans to those created in more general use treatment planning systems (TPS). METHODS: Ten spine patients at our institution were replanned in Brainlab Elements, Phillips Pinnacle3 , and Elekta Monaco. The planning target volume (PTV) included the vertebral body (in either the thoracic or lumbar spine), pedicles, and transverse processes. In all plans, the target was prescribed 20 Gy to 95% of the PTV. Objectives for the study included D5%<25 Gy and spinal cord D0.035cc < 14 Gy. Plans were evaluated by the satisfaction of the objectives as well total monitor units (MU), gradient index (GI), conformity index (CI), and dose gradient (distance between 100% and 50% isodose lines) in a selected slice between the vertebral body and spinal cord. RESULTS: All TPS produced clinically acceptable plans. The sharpest dose gradient was achieved with Elements (mean 3.3 ± 0.2 mm). This resulted in lowest spinal cord maximum point doses (6.6 ± 1.0 Gy). Gradient indices were also the smallest for Elements (3.6 ± 0.5). Further improvement in gradient index and spinal cord sparing were not performed due to the subsequent violation of the PTV D5% < 25 Gy constraint or the loss of conformity due to the loss of coverage at the PTV-spinal canal interface. CONCLUSIONS: Brainlab Elements planning which relies on arc duplication to specifically optimize for spine anatomy did result in dosimetrically superior plans while holding prescription levels constant. While any planning system can improve upon specific dosimetric objectives, the simultaneous satisfaction of all constraints was best achieved with Brainlab Elements.

Shifts in phenological distributions reshape interaction potential in natural communities.

Climate change has changed the phenologies of species worldwide, but it remains unclear how these phenological changes will affect species interactions and the structure of natural communities. Using a novel approach to analyse long-term data of 66 amphibian species pairs across eight communities, we demonstrate that phenological shifts can significantly alter the interaction potential of coexisting competitors. Importantly, these changes in interaction potential were mediated by non-uniform, species-specific shifts in entire phenological distributions and consequently could not be captured by metrics traditionally used to quantify phenological shifts. Ultimately, these non-uniform shifts in phenological distributions increased the interaction potential for 25% of species pairs (and did not reduce interaction potential for any species pair), altering temporal community structure and potentially increasing interspecific competition. These results demonstrate the potential of phenological shifts to reshape temporal structure of natural communities, emphasising the importance of considering entire phenological distributions of natural populations.

A method to predict patient-specific table coordinates for quality assurance in external beam radiation therapy.

PURPOSE: While external beam radiotherapy treatment planning determines nearly every mechanical and dosimetric parameter of the linear accelerator (LINAC), the table coordinates in all three dimensions are generally unknown until initial patient setup at the LINAC. Knowing these parameters in advance could help verify the direction of patient shifts and prevent wrong-site errors. This study aims to determine the feasibility and accuracy of table coordinate prediction for indexed immobilization devices. METHODS: A total of 303 table coordinates were predicted for patients on Varian and Elekta linear accelerators with immobilization devices including Orfit mask with baseplate, wingboard, breastboard and BodyFix. Predictions were made for all three spatial dimensions except for Body Fix setups due to the lack of a radiographically apparent indexing-related landmark. Coordinates were predicted by measuring baseline table coordinates in all dimensions at specified landmark positions. RESULTS: Predictions were accurate within 2 cm for 86% of coordinates (71% within 1 cm). Table coordinates were predicted most accurately for head and neck patients with a base plate and the most difficult prediction was in the lateral direction for breastboard patients. CONCLUSIONS: With proper indexing, table coordinates can be predicted with reasonable accuracy. The data suggest an action of level of 2 cm with certain exceptions for specific immobilization devices and directions.

Thrombelastography Suggests Hypercoagulability in Patients with Renal Dysfunction and Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to quantify coagulopathy using thrombelastography (TEG) in patients with renal dysfunction and intracerebral hemorrhage (ICH). METHODS: We reviewed patients admitted with spontaneous ICH between November 2009 and May 2015. TEG was performed at the time of admission. Creatinine clearance (CCr) was calculated using the Cockroft-Gault equation. Patients were divided into 2 groups based on normal (CCr ≥ 90) or reduced renal function (CCr < 90). Multivariable regression models were conducted to compare the differences of TEG components. RESULTS: A total of 120 patients were included in the analysis. The normal CCr group was younger (56.1 versus 62.3 years, P < .01), was more often male (73.6% versus 53.7%, P = .03), and had higher mean admission hemoglobin (14.2 versus 13.2 mEq/L, P < .01) than the reduced renal function group. The 2 groups were similar with respect to antiplatelet or anticoagulant use, coagulation studies, and baseline ICH volume. Following multivariate analysis, the reduced renal function group was found to have shorter K (1.5 versus 2.2 min, P = 004), increased angle (66 versus 62.2 degrees, P = .04), increased MA (67.3 versus 62.3, P = .02), and increased G (11.3 versus 9.9 dynes/cm2, P = .04) compared with the normal group. Mortality, poor functional outcome (modified Rankin Scale score 4-6), hematoma enlargement, hospital length of stay, and surgical interventions were not different between the 2 groups. CONCLUSIONS: Patients with ICH and reduced CCr display faster clotting rate and increased clot strength, suggesting that patients with renal dysfunction present with a relatively hypercoagulable state based on TEG parameters thought to reflect platelet activity.

Reversal of the Migratory and Invasive Phenotype of Ras-Transfected Mammary Cells by Photodynamic Therapy Treatment.

Photodynamic therapy (PDT) is a non-thermal technique for inducing tumor damage following administration of a light-activated photosensitizing drug (PS). In a previous work we found that PDT induces cytoskeleton changes in HB4a-Ras cells (human mammary breast carcinoma HB4a cells transfected with the RAS oncogene). In the present work we have studied the migratory and invasive features and the expression of proteins related to these processes on HB4a-Ras cells after three successive cycles of PDT using different PSs: 5-aminolevulinic acid (ALA), Verteporfin (Verte), m-tetrahydroxyphenylchlorin (m-THPC), and Merocyanine 540 (MC). A slight (1.25- to 2-fold) degree of resistance was acquired in cell populations subjected to the three successive PDT treatments. However, complete cell killing was achieved after a light dose increase. Regardless of the PS employed, all the PDT-treated populations had shorter stress fibres than the untreated control HB4a-Ras cells, and the number of dorsal stress fibres was decreased in the PDT-treated populations. E-Cadherin distribution, which was already aberrant in HB4a-Ras cells, became even more diffuse in the PDT-treated populations, though its expression was increased in some of them. The strong migratory and invasive ability of HB4a-Ras cells in vitro was impaired in all the PDT-treated populations, with a behavior that was similar to the parental non-tumoral HB4a cells. MMP-2 and -9 metalloproteinase activities were also impaired in the PDT-treated populations. The evidence presented herein suggests that the cells surviving PDT would be less metastatic than the initial population. These findings encourage the use of PDT in combination with other treatments such as intraoperative or post-surgery therapeutic procedures. J. Cell. Biochem. 118: 464-477, 2017. © 2016 Wiley Periodicals, Inc.

NCCN Guidelines Insights: Hepatobiliary Cancers, Version 1.2017.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

Methods for the detection of reactive oxygen species employed in the identification of plant photosensitizers.

Over the past ten years, alternative methods for the rapid screening of PSs have been developed. In the present work, a study was undertaken to correlate the phototoxicity of plant extracts on either prokaryotic or eukaryotic cells, with the total oxidation status (TOS) as well as with their ability to produce 1O2. Results demonstrated that the extracts containing PSs that were active either on eukaryotic cells or bacteria increased their TOS after illumination, and that there was a certain degree of positive correlation between the extract phototoxic efficacy and TOS levels. The production of 1O2 by the illuminated extracts was indirectly measured by the use of the fluorescence of "singlet oxygen sensor green", which is a method that has proved highly sensitive for such measurement. 1O2 was detectable only upon illumination of the most active extracts. In addition, the oxidation of tryptophan and was employed as a method capable of measuring ROS generated by both type I and II ROS reactions. However, it turned out to be not sensitive enough to detect the species generated by plant extracts. Results demonstrated that the TOS method, initially developed to measure the oxidant status in plasma, can be readily applied to plant extracts. Unlike the method used to detect 1O2, the method employed for the detection of TOS proved to be accurate, since all the extracts that displayed a high phototoxic activity on either prokaryotic or eukaryotic cells, presented high TOS levels after illumination.