Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.

A Review of Biodegradable Plastics: Chemistry, Applications, Properties, and Future Research Needs.

Environmental concerns over waste plastics' effect on the environment are leading to the creation of biodegradable plastics. Biodegradable plastics may serve as a promising approach to manage the issue of environmental accumulation of plastic waste in the ocean and soil. Biodegradable plastics are the type of polymers that can be degraded by microorganisms into small molecules (e.g., H2O, CO2, and CH4). However, there are misconceptions surrounding biodegradable plastics. For example, the term "biodegradable" on product labeling can be misconstrued by the public to imply that the product will degrade under any environmental conditions. Such misleading information leads to consumer encouragement of excessive consumption of certain goods and increased littering of products labeled as "biodegradable". This review not only provides a comprehensive overview of the state-of-the-art biodegradable plastics but also clarifies the definitions and various terms associated with biodegradable plastics, including oxo-degradable plastics, enzyme-mediated plastics, and biodegradation agents. Analytical techniques and standard test methods to evaluate the biodegradability of polymeric materials in alignment with international standards are summarized. The review summarizes the properties and industrial applications of previously developed biodegradable plastics and then discusses how biomass-derived monomers can create new types of biodegradable polymers by utilizing their unique chemical properties from oxygen-containing functional groups. The terminology and methodologies covered in the paper provide a perspective on directions for the design of new biodegradable polymers that possess not only advanced performance for practical applications but also environmental benefits.

From farm accountancy data to environmental indicators: Assessing the environmental performance of Spanish agriculture at a regional level.

Understanding the environmental impacts of current agricultural practices is a starting point for transitioning towards sustainable agriculture, which is a goal to be achieved by the European Union. This study aims to provide a set of environmental impact indicators with which to assess and compare the environmental performance of a broad group of agricultural reference holdings at the Spanish NUTS 2 level. A life cycle assessment approach based on statistical data on farm accountancy is applied. The unit of analysis is a reference holding on which a specific crop is grown in a NUTS 2 and follows a specific management system (open-field irrigated, open-field rainfed, or greenhouse). The system boundaries are set at the farm gate, and the impact results are expressed per 1 € of net value added. For most reference holdings, the EF scores per net value added are similar regardless of their EF scores per kg commodity, suggesting a correspondence between the use of resources and the economic results. The environmental footprint is clustered into four groups. The first one accounts for 78 % of the sample and represents the holdings with the lowest impact (between 9.7·10-5 and 2.88·10-3 EF score·NVAfc-1); the second cluster groups seven reference holdings (3 herbaceous and 4 Mediterranean perennial crops) with an environmental footprint of between 3.04·10-3 and 9.01·10-3 EF score·NVAfc-1; the third group comprises four irrigated herbaceous crops holdings with the highest impact (between 1.37·10-2 and 2.13·10-2 EF score·NVAfc-1); and the last group corresponds to the holdings with economic losses (mostly herbaceous and two Mediterranean perennial crops). This research highlights the challenge of improving the competitiveness and profitability of Spanish farming. In this way, agricultural practices that generate environmental impacts without achieving their economic goals would be avoided.

Simultaneous Fe2+/Fe3+ imaging shows Fe3+ over Fe2+ enrichment in Alzheimer's disease mouse brain.

Visualizing redox-active metal ions, such as Fe2+ and Fe3+ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe2+ and Fe3+ simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe2+ or Fe3+, revealing a decreased Fe3+/Fe2+ ratio during ferroptosis and an increased Fe3+/Fe2+ ratio in Alzheimer's disease mouse brain. The elevated Fe3+/Fe2+ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe3+ and/or conversion of Fe2+ to Fe3+. Our sensors can provide deep insights into the biological roles of labile iron redox cycling.

Dataset to monitor regionalised environmental impacts of the main agricultural products in Spain.

Estimating the average environmental impacts of a representative crop in a specific region is a helpful starting point from which to propose improvements in the agricultural sector. However, data collection from official representative sources is complex, and often they require subsequent treatment to be transformed into meaningful inventory data. This article shows a comprehensive dataset for obtaining inventory data and developing an environmental life cycle impact assessment of representative agricultural production corresponding to reference holdings at a regional level (NUTS 2) in Spain. The dataset comprises Excel files with the data compiled from secondary sources to be used in the assessment and the R code scripts to transform the data into relevant inventory data to estimate the environmental impacts of the reference holdings. This dataset is a reliable tool for researchers and other potential users to be used as a secondary information source for further studies. It can also be used to estimate the environmental impacts of the farming activity of agri-food products in other regions or countries by collecting similar data for the specific region and adjusting the R code.

Novel reinforcement of corrugated nanofiber tissue-engineered vascular graft to prevent aneurysm formation for arteriovenous shunts in an ovine model.

Objective: Many patients who require hemodialysis treatment will often require a prosthetic graft after multiple surgeries. However, the patency rate of grafts currently available commercially has not been satisfactory. Tissue engineering vascular grafts (TEVGs) are biodegradable scaffolds created to promote autologous cell proliferation and functional neotissue regeneration and, accordingly, have antithrombogenicity. Therefore, TEVGs can be an alternative prosthesis for small diameter grafts. However, owing to the limitations of the graft materials, most TEVGs are rigid and can easily kink when implanted in limited spaces, precluding future clinical application. Previously, we developed a novel corrugated nanofiber graft to prevent graft kinking. Reinforcement of these grafts to ensure their safety is required in a preclinical study. In the present study, three types of reinforcement were applied, and their effectiveness was examined using large animals. Methods: In the present study, three different reinforcements for the graft composed of corrugated poly-ε-caprolactone (PCL) blended with poly(L-lactide-co-ε-caprolactone) (PLCL) created with electrospinning were evaluated: 1) a polydioxanone suture, 2) a 2-0 polypropylene suture, 3) a polyethylene terephthalate/polyurethane (PET/PU) outer layer, and PCL/PLCL as the control. These different grafts were then implanted in a U-shape between the carotid artery and jugular vein in seven ovine models for a total of 14 grafts during a 3-month period. In evaluating the different reinforcements, the main factors considered were cell proliferation and a lack of graft dilation, which were evaluated using ultrasound examinations and histologic and mechanical analysis. Results: No kinking of the grafts occurred. Overall, re-endothelialization was observed in all the grafts at 3 months after surgery without graft rupture or calcification. The PCL/PLCL grafts and PCL/PLCL grafts with a polydioxanone suture showed high cell infiltration; however, they had become dilated 10 weeks after surgery. In contrast, the PCL/PLCL graft with the 2-0 suture and the PCL/PLCL graft covered with a PET/PU layer did not show any graft expansion. The PCL/PLCL graft covered with a PET/PU layer showed less cell infiltration than that of the PCL/PLCL graft. Conclusions: Reinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

Location matters: Offset in tissue-engineered vascular graft implantation location affects wall shear stress in porcine models.

Objective: Although surgical simulation using computational fluid dynamics has advanced, little is known about the accuracy of cardiac surgical procedures after patient-specific design. We evaluated the effects of discrepancies in location for patient-specific simulation and actual implantation on hemodynamic performance of patient-specific tissue-engineered vascular grafts (TEVGs) in porcine models. Methods: Magnetic resonance angiography and 4-dimensional (4D) flow data were acquired in porcine models (n = 11) to create individualized TEVGs. Graft shapes were optimized and manufactured by electrospinning bioresorbable material onto a metal mandrel. TEVGs were implanted 1 or 3 months postimaging, and postoperative magnetic resonance angiography and 4D flow data were obtained and segmented. Displacement between intended and observed TEVG position was determined through center of mass analysis. Hemodynamic data were obtained from 4D flow analysis. Displacement and hemodynamic data were compared using linear regression. Results: Patient-specific TEVGs were displaced between 1 and 8 mm during implantation compared with their surgically simulated, intended locations. Greater offset between intended and observed position correlated with greater wall shear stress (WSS) in postoperative vasculature (P < .01). Grafts that were implanted closer to their intended locations showed decreased WSS. Conclusions: Patient-specific TEVGs are designed for precise locations to help optimize hemodynamic performance. However, if TEVGs were implanted far from their intended location, worse WSS was observed. This underscores the importance of not only patient-specific design but also precision-guided implantation to optimize hemodynamics in cardiac surgery and increase reproducibility of surgical simulation.

Lower Back Pain as an Occupational Hazard Among Ugandan Health Workers.

Background: Lower back pain is a public health concern affecting 70-85% of the world's population. There is paucity of published data on the prevalence, disability and risk factors for lower back pain among health workers in Uganda. Objective: To determine the frequency rate (note that is it implicit that frequency is a rate like incidence so including rate seems redundant here. This is bounded by zero and infinity. In contrast, prevalence is bounded by 0 and 1 and is thus a proportion not a rate) of lower back pain and its associated risks amongst health professionals in the Arua District of Uganda. Methods: Cross-sectional descriptive study of 245 consecutive participants conducted during February-April 2020. We stratified risks as individual or work related and analyzed the data using IBM SPSS version 25. Chi-square was used to measure the significance of association between categorical variables at 95% confidence interval, regarding a p ≤ 0.05 as significant. Results: The mean age of participants was 40.87 years ± 8.74 (SD), with female predominance (69.8%). Majority were either general nurses or midwives (64.9%) and more than half had practiced for over 6-10 years. The frequency rate of lower back pain was 39.6% (n = 97). Individual factors associated with LBP were; cigarette smoking (X2 = 33.040; P ≤ 0.001), alcohol consumption (X2 = 13.581; P ≤ 0.001), age (X2 = 14.717; P = 0.002), and female gender (X2 = 4.802; P = 0.028). The work related factors significantly associated with lower back pain were: being a nurse/midwife (X2 = 9.829; P = 0.007), working in the outpatient department (X2 = 49.752; P ≤ 0.001), bending (X2 = 43.912; P ≤ 0.001), lifting (X2 = 33.279; P < 0.001), over standing (X2 = 40.096; P ≤ 0.001), being in awkward positions (X2 = 15.607; P= < 0.001), and pushing patients (X2 = 21.999; P ≤ 0.001). Conclusion: The frequency rate of low back pain was high amongst health workers and its main associated individual and work related factors could have been prevented. Health workers should strike a balance between caring for their personal back-health and meeting clients' needs while manually handling patients. Ergonomic structuring, job organization, back health care courses and use of assistive equipment could reduce such occupational hazards in our low resourced settings.

Software Training in HEP.

The long-term sustainability of the high-energy physics (HEP) research software ecosystem is essential to the field. With new facilities and upgrades coming online throughout the 2020s, this will only become increasingly important. Meeting the sustainability challenge requires a workforce with a combination of HEP domain knowledge and advanced software skills. The required software skills fall into three broad groups. The first is fundamental and generic software engineering (e.g., Unix, version control, C++, and continuous integration). The second is knowledge of domain-specific HEP packages and practices (e.g., the ROOT data format and analysis framework). The third is more advanced knowledge involving specialized techniques, including parallel programming, machine learning and data science tools, and techniques to maintain software projects at all scales. This paper discusses the collective software training program in HEP led by the HEP Software Foundation (HSF) and the Institute for Research and Innovation in Software in HEP (IRIS-HEP). The program equips participants with an array of software skills that serve as ingredients for the solution of HEP computing challenges. Beyond serving the community by ensuring that members are able to pursue research goals, the program serves individuals by providing intellectual capital and transferable skills important to careers in the realm of software and computing, inside or outside HEP.

Reducing Antisolvent Use in the STRAP Process by Enabling a Temperature-Controlled Polymer Dissolution and Precipitation for the Recycling of Multilayer Plastic Films.

The recently reported processing strategy called solvent-targeted recovery and precipitation (STRAP) enables deconstruction of multilayer plastic packaging films into their constituent resins by selective dissolution. It uses a series of solvent washes that are guided by thermodynamic calculations of polymer solubility. In this work, the use of antisolvents in the STRAP process was reduced and solvent mixtures were considered to enable the temperature-controlled dissolution and precipitation of the target polymers in multilayer films. This was considered as a means to further improve the STRAP process and its estimated costs. Two STRAP approaches were compared based on different polymer precipitation techniques: precipitation by the addition of an antisolvent (STRAP-A) and precipitation by decreasing the solvent temperature (STRAP-B). Both approaches were able to separate the constituent polymers in a post-industrial film composed primarily of polyethylene (PE), ethylene vinyl alcohol (EVOH), and polyethylene terephthalate (PET) with near 100 % material efficiency. Technoeconomic analysis indicates that the minimum selling price (MSP) of the recycled resins with STRAP-B is 21.0 % lower than that achieved with STRAP-A. This provides evidence that thermally driven polymer precipitation is an option to reduce the use of antisolvents, making the STRAP process more economically and environmentally attractive. A third process, STRAP-C, was demonstrated with another post-industrial multilayer film of a different composition. The results demonstrate that this process can also recover polymers at similar costs to those of virgin resins, indicating that the STRAP technology is flexible and can remain economically competitive as the plastic feed complexity is increased.

A serum-based DNA methylation assay provides accurate detection of glioma.

BACKGROUND: The detection of somatic mutations in cell-free DNA (cfDNA) from liquid biopsy has emerged as a noninvasive tool to monitor the follow-up of cancer patients. However, the significance of cfDNA clinical utility remains uncertain in patients with brain tumors, primarily because of the limited sensitivity cfDNA has to detect real tumor-specific somatic mutations. This unresolved challenge has prevented accurate follow-up of glioma patients with noninvasive approaches. METHODS: Genome-wide DNA methylation profiling of tumor tissue and serum cfDNA of glioma patients. RESULTS: Here, we developed a noninvasive approach to profile the DNA methylation status in the serum of patients with gliomas and identified a cfDNA-derived methylation signature that is associated with the presence of gliomas and related immune features. By testing the signature in an independent discovery and validation cohorts, we developed and verified a score metric (the "glioma-epigenetic liquid biopsy score" or GeLB) that optimally distinguished patients with or without glioma (sensitivity: 100%, specificity: 97.78%). Furthermore, we found that changes in GeLB score reflected clinicopathological changes during surveillance (eg, progression, pseudoprogression, and response to standard or experimental treatment). CONCLUSIONS: Our results suggest that the GeLB score can be used as a complementary approach to diagnose and follow up patients with glioma.

Review of Neurologic Comorbidities in Hospitalized Patients With Opioid Abuse.

PURPOSE OF REVIEW: To determine the prevalence and burden of neurologic comorbidities in hospitalized patients with opioid abuse. RECENT FINDINGS: From 1 year of hospital discharges, 2,182 patients with opioid abuse were identified (prevalence 6.3%), with abuse greater among younger patients (p < 0.0001), women (p < 0.0001), Whites (p < 0.0001), and urban population (p = 0.028). Matching for age, sex, race, and urban-rural residence, 347 patients were reviewed, and 179 (52%) had a neurologic comorbidity. The comorbidities frequently overlapped and included encephalopathy (130), neuromuscular disorders (42), seizures (23), spine disorders (23), strokes (20), CNS infections (3), and movement disorders (2). Abuse patients with neurologic comorbidities experienced substantially greater number of hospital and intensive care unit days and mortality, independent of overdose. SUMMARY: Neurologic comorbidities are a frequent and heretofore underappreciated contributor to the disease burden of hospitalized patients with opioid abuse. The importance of neurologic comorbidities should be included in the public health discussions surrounding the opioid epidemic.

A Novel Negative Pressure-Flow Waveform to Ventilate Lungs for Normothermic Ex Vivo Lung Perfusion.

Ex vivo lung perfusion (EVLP) is increasingly used to treat and assess lungs before transplant. Minimizing ventilator induced lung injury (VILI) during EVLP is an important clinical need, and negative pressure ventilation (NPV) may reduce VILI compared with conventional positive pressure ventilation (PPV). However, it is not clear if NPV is intrinsically lung protective or if differences in respiratory pressure-flow waveforms are responsible for reduced VILI during NPV. In this study, we quantified lung injury using novel pressure-flow waveforms during normothermic EVLP. Rat lungs were ventilated-perfused ex vivo for 2 hours using tidal volume, positive end-expiratory pressure (PEEP), and respiratory rate matched PPV or NPV protocols. Airway pressures and flow rates were measured in real time and lungs were assessed for changes in compliance, pulmonary vascular resistance, oxygenation, edema, and cytokine secretion. Negative pressure ventilation lungs demonstrated reduced proinflammatory cytokine secretion, reduced weight gain, and reduced pulmonary vascular resistance (p < 0.05). Compliance was higher in NPV lungs (p < 0.05), and there was no difference in oxygenation between the two groups. Respiratory pressure-flow waveforms during NPV and PPV were significantly different (p < 0.05), especially during the inspiratory phase, where the NPV group exhibited rapid time-dependent changes in pressure and airflow whereas the PPV group exhibited slower changes in airflow/pressures. Lungs ventilated with PPV also had a greater transpulmonary pressure (p < 0.05). Greater improvement in lung function during NPV EVLP may be caused by favorable airflow patterns and/or pressure dynamics, which may better mimic human respiratory patterns.

Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C.

Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. CONCLUSIONS: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

Corrugated nanofiber tissue-engineered vascular graft to prevent kinking for arteriovenous shunts in an ovine model.

OBJECTIVE: Prosthetic grafts are often needed in open vascular procedures. However, the smaller diameter prosthetic grafts (<6 mm) have low patency and often result in complications from infection. Tissue-engineered vascular grafts (TEVGs) are a promising replacement for small diameter prosthetic grafts. TEVGs start as a biodegradable scaffold to promote autologous cell proliferation and functional neotissue regeneration. Owing to the limitations of graft materials; however, most TEVGs are rigid and easily kinked when implanted in limited spaces, which precludes clinical application. We have developed a novel corrugated nanofiber graft to prevent kinking. METHODS: TEVGs with corrugated walls (5-mm internal diameter by 10 cm length) were created by electrospinning a blend of poly-ε-caprolactone and poly(L-lactide-co-caprolactone). The biodegradable grafts were then implanted between the carotid artery and the external jugular vein in a U-shape using an ovine model. TEVGs were implanted on both the left and right side of a sheep (n = 4, grafts = 8). The grafts were explanted 1 month after implantation and inspected with mechanical and histologic analyses. Graft patency was confirmed by measuring graft diameter and blood flow velocity using ultrasound, which was performed on day 4 and every following week after implantation. RESULTS: All sheep survived postoperatively except for one sheep that died of acute heart failure 2 weeks after implantation. The graft patency rate was 87.5% (seven grafts out of eight) with one graft becoming occluded in the early phase after implantation. There was no significant kinking of the grafts. Overall, endothelial cells were observed in the grafts 1 month after the surgeries without graft rupture, calcification, or aneurysmal change. CONCLUSIONS: Our novel corrugated nanofiber vascular graft displayed neotissue formation without kinking in large animal model.

In vivo implantation of 3-dimensional printed customized branched tissue engineered vascular graft in a porcine model.

BACKGROUND: The customized vascular graft offers the potential to simplify the surgical procedure, optimize physiological function, and reduce morbidity and mortality. This experiment evaluated the feasibility of a flow dynamic-optimized branched tissue engineered vascular graft (TEVG) customized based on medical imaging and manufactured by 3-dimensional (3D) printing for a porcine model. METHODS: We acquired magnetic resonance angiography and 4-dimensional flow data for the native anatomy of the pigs (n = 2) to design a custom-made branched vascular graft of the pulmonary bifurcation. An optimal shape of the branched vascular graft was designed using a computer-aided design system informed by computational flow dynamics analysis. We manufactured and implanted the graft for pulmonary artery (PA) reconstruction in the porcine model. The graft was explanted at 4 weeks after implantation for further evaluation. RESULTS: The custom-made branched PA graft had a wall shear stress and pressure drop (PD) from the main PA to the branch PA comparable to the native vessel. At the end point, magnetic resonance imaging revealed comparable left/right pulmonary blood flow balance. PD from main PA to branch between before and after the graft implantation was unchanged. Immunohistochemistry showed evidence of endothelization and smooth muscle layer formation without calcification of the graft. CONCLUSIONS: Our animal model demonstrates the feasibility of designing and implanting image-guided, 3D-printed, customized grafts. These grafts can be designed to optimize both anatomic fit and hemodynamic properties. This study demonstrates the tremendous potential structural and physiological advantages of customized TEVGs in cardiac surgery.

Different degradation rates of nanofiber vascular grafts in small and large animal models.

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.

Radiation Safety Observations Associated with 177Lu Dotatate Patients.

Lutetium-177 dotatate, marketed under the name Lutathera®, is proving to be a valuable tool for physicians treating patients with neuroendocrine somatostatin-receptive tumors. Treatment consists of four cycles of 7.4 GBq of Lu dotatate infused intravenously over 30 to 40 minutes. This paper focuses on the radiation safety implications of patients undergoing Lu dotatate treatments at two large medical centers in the United States under the manufacturer's Expanded Access Protocol. Radiation safety precautions are described for the treatment of patients to control for radiation exposure and potential contamination. Ideally, the room used for administration should have a toilet, or one that is in close proximity, and covering should be provided to minimize contamination and clean up. The patient will meet the requirements in 10 CFR Part 35.75 for immediate release based on administered activity or measured exposure rate, but will need to be provided with written instruction on how to keep doses to other individuals ALARA. Disposal of the radioactive waste from Lu dotatate therapy can present some hazard control issues due to the long-lived Lu contaminant.Based on our experience, Lu dotatate therapy is an effective outpatient procedure that can safely occur in any hospital procedural room without the need for additional local shielding. Administration can be accomplished safely with attention paid to the administration set-up and proper administration procedures. Exposure to staff or to adjacent areas is minimal.