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Lung transplantation has been well described for COVID-19 patients in the acute setting, but less so for the resulting pulmonary sequelae. We share one of the first cases of lung transplantation for post COVID-19 pulmonary fibrosis. A 52-year-old female developed COVID-19 in July 2020 and mounted a partial recovery, but went on to have declining function over the ensuing three months and developed fibrocystic lung changes. She underwent bilateral lung transplantation and recovered rapidly, was discharged home POD 14, and has done well in follow-up. We demonstrate that lung transplantation is an acceptable therapy to treat post COVID-19 pulmonary fibrosis.

Objective To assess the efficacy of an intern surgical skills curriculum involving a boot camp for core open and laparoscopic skills, self-guided practice with positive and negative incentives, and semiannual performance evaluations. Design Longitudinal cohort study. Setting Academic tertiary care center. Participants Intervention group (n = 15): residents who completed the intern surgical skills curriculum and had performance evaluations in fall of intern year, spring of intern year, and fall of second year. Control group (n = 8): second-year residents who were 1 year ahead of the intervention group in the same residency program, did not participate in the curriculum, and had performance evaluations in fall of second year. Results In fall of second year of residency, the intervention group had better performance (presented as median values with interquartile ranges) than the control group on one-hand ties (left hand: 9.1 [6.3-10.1] vs 14.6 [13.5-15.4] seconds, p = 0.007; right hand: 8.7 [8.5-9.6] vs 11.5 [9.9-16.8] seconds, p = 0.039). The intervention group also had better performance on all open suturing skills, including mattress suturing (vertical: 33.4 [30.0-40.0] vs 55.8 [50.0-67.6] seconds, p = 0.001; horizontal: 28.7 [27.3-39.9] vs 52.7 [40.7-57.8] seconds, p = 0.003), and a water-filled glove clamp, divide, and ligate task (28.0 [25.0-31.0] vs 59.1 [53.0-93.0] seconds, p < 0.001). Finally, the intervention group had better performance on all laparoscopic skills, including peg transfer (66.0 [59.0-82.0] vs 95.2 [87.5-101.5] seconds, p = 0.018), circle cut (82.0 [69.0-124.0] seconds vs 191.8 [155.5-231.5] seconds, p = 0.002), and intracorporeal suturing (195.0 [117.0-200.0] seconds vs 359.5 [269.0-450.0] seconds, p = 0.002). Conclusions Implementation of a comprehensive surgical skills curriculum was associated with improved performance on core open and laparoscopic skills. Further research is needed to understand and optimize motivational factors for deliberate practice and surgical skill acquisition.

Introduction Blood-brain barrier (BBB) disruption and subsequent neuro-inflammation occur following traumatic brain injury (TBI), resulting in a spectrum of human nervous system disorders. [99mTc]Tc-tilmanocept is a receptor-binding radiopharmaceutical FDA-approved for sentinel lymph node mapping. We hypothesize that after an intravenous (i.v.) injection, [99mTc]Tc-tilmanocept, will traverse a disrupted BBB and bind to CD206-bearing microglial cells. Methods Age-matched mice were divided into three groups: 5-days post TBI (n = 4), and 5-days post sham (n = 4), and naive controls (n = 4). IRDye800CW-labeled [99mTc]Tc-tilmanocept (0.15 nmol per gram body weight) and FITC-labeled bovine serum albumin (FITC-BSA) were injected (i.v.) into each mouse. Mice were imaged with a high-resolution gamma camera for 45 min. Immediately after imaging, the brains were perfused with fixative, excised, imaged with a fluorescence scanner, assayed for radioactivity, and prepared for histology. Results In vivo nuclear imaging, ex vivo fluorescence imaging, ex vivo gamma well counting, and histo-microscopy demonstrated enhanced tilmanocept uptake in the TBI region. The normalized [99mTc]Tc-tilmanocept uptake value from nuclear imaging and the maximum pixel intensity from fluorescence imaging of the TBI group (1.12 ± 0.12 and 2288 ± 278 a.u., respectively) were significantly (P Conclusion [99mTc]Tc-tilmanocept traverses disrupted blood-brain barrier and localizes within the injured region. Advances in knowledge and implications for patient care [99mTc]Tc-tilmanocept could serve as an imaging biomarker for TBI-associated neuroinflammation and any disease process that involves a disruption of the blood-brain barrier.

Species is the fundamental unit to quantify biodiversity. In recent years, the model yeast Saccharomyces cerevisiae has seen an increased number of studies related to its geographical distribution, population structure, and phenotypic diversity. However, seven additional species from the same genus have been less thoroughly studied, which has limited our understanding of the macroevolutionary events leading to the diversification of this genus over the last 20 million years. Here, we show the geographies, hosts, substrates, and phylogenetic relationships for approximately 1,800 Saccharomyces strains, covering the complete genus with unprecedented breadth and depth. We generated and analyzed complete genome sequences of 163 strains and phenotyped 128 phylogenetically diverse strains. This dataset provides insights about genetic and phenotypic diversity within and between species and populations, quantifies reticulation and incomplete lineage sorting, and demonstrates how gene flow and selection have affected traits, such as galactose metabolism. These findings elevate the genus Saccharomyces as a model to understand biodiversity and evolution in microbial eukaryotes., Some computations were performed on Tirant III of the Spanish Supercomputing Network (“Servei d’Informàtica de la Universitat de València”) under the project BCV-2021-1-0001 granted to DP, while others were performed at the Wisconsin Energy Institute and the Center for High-Throughput Computing of the University of Wisconsin–Madison. During a portion of this project, DP was a researcher funded by the European Union’s Horizon 2020 research and innovation program Marie Sklodowska-Curie, grant agreement No. 747775, the Research Council of Norway (RCN) grant Nos. RCN 324253 and 274337, and the Generalitat Valenciana plan GenT grant No. CIDEGENT/2021/039. D.P. is a recipient of an Illumina Grant for Illumina Sequencing Saccharomyces strains in this study. Q.K.L. was supported by the National Science Foundation under Grant No. DGE-1256259 (Graduate Research Fellowship) and the Predoctoral Training Program in Genetics, funded by the National Institutes of Health (5T32GM007133). This material is based upon work supported in part by the Great Lakes Bioenergy Research Center, Office of Science, Office of Biological and Environmental Research under Award Numbers DE-SC0018409 and DE-FC02-07ER64494; the National Science Foundation under Grant Nos. DEB-1253634, DEB−1442148, and DEB-2110403; and the USDA National Institute of Food and Agriculture Hatch Project Number 1020204. C.T.H. is an H. I. Romnes Faculty Fellow, supported by the Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation. QMW was supported by the National Natural Science Foundation of China (NSFC) under Grant Nos. 31770018 and 31961133020. C.R.L. holds the Canada Research Chair in Cellular Systems and Synthetic Biology, and his research on wild yeast is supported by an NSERC Discovery Grant.

Exposure to chronic hyperglycemia because of diabetes mellitus can lead to development and progression of diabetic kidney disease (DKD). We recently reported that reduced superoxide production is associated with mitochondrial dysfunction in the kidneys of mouse models of type 1 DKD. We also demonstrated that humans with DKD have significantly reduced levels of mitochondrion-derived metabolites in their urine. Here we examined renal superoxide production in a type 2 diabetes animal model, the db/db mouse, and the role of a mitochondrial protectant, MTP-131 (also called elamipretide, SS-31, or Bendavia) in restoring renal superoxide production and ameliorating DKD. We found that 18-week-old db/db mice have reduced renal and cardiac superoxide levels, as measured by dihydroethidium oxidation, and increased levels of albuminuria, mesangial matrix accumulation, and urinary H2O2. Administration of MTP-131 significantly inhibited increases in albuminuria, urinary H2O2, and mesangial matrix accumulation in db/db mice and fully preserved levels of renal superoxide production in these mice. MTP-131 also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice. These results indicate that, in type 2 diabetes, DKD is associated with reduced renal and cardiac superoxide levels and that MTP-131 protects against DKD and preserves physiological superoxide levels, possibly by regulating cardiolipin remodeling.

OBJECTIVE The index for mortality prediction after cardiac transplantation (IMPACT) risk score incorporates 12 preoperative recipient-specific variables, and has been validated as an accurate predictor of short- and long-term mortality after orthotopic heart transplantation (OHTx). We believe it can also be used to predict hospital costs, and we hypothesize that higher preoperative IMPACT risk scores are associated with increased hospital resource consumption. METHODS All OHTx patients ≥18 years of age at our institution were reviewed from 1 January 2000 to 31 December 2014. Total index hospitalization costs post-transplant were extracted and presented in 2014 consumer price index inflation-adjusted US dollars. Patients were stratified into quartiles (Q) according to IMPACT risk scores. Logarithmic transformation normalized cost data, and linear regression assessed for correlation. A comparison of cost between Q of IMPACT risk score was performed using rank-sum and Kruskal-Wallis tests. Survival was estimated using the Kaplan-Meier method. RESULTS Three hundred fifty-six (n = 356) OHTx were performed during the study period. The median IMPACT score for the cohort was five (interquartile range [IQR] 3-6). Eight (2.2%) patients died within 30-days and 1-year Kaplan-Meier survival was 88.3%. The median length of stay (LOS) was 16 (IQR 14-24) days. The median hospital cost for index admission was $222 200 (IQR:$169 200-$313 700). Median LOS was longer in Q4 vs Q1 (18 days vs 15 days, P = .01) and index hospital costs in Q4 were significantly higher compared to Q1 patients ($280 400 vs $205 000, P

Background: Increasing opioid-related deaths have heightened focus on combating the opioid epidemic. The impact of surgical trainees on opioid-related deaths is unclear, and there is little data examining the association between trainee pain management education and opioid prescribing practices. Methods: An anonymous, online survey was distributed to members of the Resident and Associate Society of the American College of Surgeons. The survey covered five themes: education and knowledge, prescribing practices, clinical case scenarios, policy, and beliefs and attitudes. Linear mixed models were used to evaluate the influence of respondent characteristics on reported morphine milligram equivalents (MME) prescribed for common general surgery clinical scenarios. Results: Of 427 respondents, 54 percent indicated receiving training in postoperative pain management during medical school and 66 percent during residency. Only 35 percent agreed that they had received adequate training in prescribing opioids. There was a significant association between undergoing formal pain management training in medical school and prescribing fewer MME for common outpatient general surgery scenarios (94 ± 15.2 vs 108 ± 15.0; p = 0.003). Similarly, formal pain management training in residency was associated with prescribing fewer MME in the survey scenarios (92.6 ± 15.2 vs 109 ± 15.2; p = 0.002). Conclusion: In this survey, nearly two-thirds of surgical residents felt that they were inadequately trained in opioid prescribing. Our findings additionally suggest that improving education may result in increased resident comfort with managing surgical pain, potentially leading to more responsible opioid prescribing. Further work will facilitate residency programs’ development of educational curricula for opioid prescribing best practices.

Background Lung transplantation for patients with end-stage lung disease continues to grow worldwide. Increasing demand for this therapy generates significant waitlist mortality, indicating that alternative sources of donor lungs, such as older donors, are needed. The effect of the donor–recipient age relationship on outcomes remains unclear. Methods A retrospective review of the United Network for Organ Sharing Standard Transplant Analysis and Research database was performed for adult lung recipients from 2005 to 2015. Variables examined included donor age, recipient age, listing diagnosis, episodes of acute cellular rejection in the first year, and survival. Both donors and recipients were stratified according to age ranges. Survival was compared with the log-rank test. Propensity score matching was done stratifying donors younger than 60 years versus older than 60 years for the recipient population of 60 to 69 years. Results From May 2005 to February 2015, 15,844 patients underwent lung transplantation. Unadjusted comparisons of donor-to-recipient age showed that older donor age appeared to be more relevant for recipients 60 to 69 years old (p = 0.002). Nevertheless, when propensity matching was done based on relevant covariates for recipients in this age range by donors younger or older than 60 years, there were no differences in survival. Conclusions Our results suggest that even though donor and recipient age may be important in lung transplantation, the interplay between donor and recipient age alone is not an independent determinant of survival. Careful selection of lungs from donors older than 60 years old should be exercised, taking into consideration the totality of donor demographics and risk factors rather than dismissing lungs based on advanced age alone.

An unmet need for the clinical management of chronic kidney disease is a predictive tool of kidney function during the first decade of the disease, when there is silent loss of glomerular function. The objective of this study was to demonstrate receptor-mediated binding of tilmanocept to CD206 within the kidney and provide evidence of kinetic sensitivity of this binding to renal function. Methods: Rats were positioned in a PET scanner with the liver and kidneys within the field of view. After an intravenous injection of (68)Ga-IRDye800-tilmanocept, using 1 of 2 scaled molar doses (0.02 nmol/g, n = 5; or 0.10 nmol/g, n = 5), or coinjection (n = 3) of (68)Ga-IRDye800-tilmanocept (0.10 nmol/g) and unlabeled tilmanocept (5.0 nmol/g), or a negative control, (68)Ga-IRDye800-DTPA-galactosyl-dextran (0.02 nmol/g, n = 5), each animal was imaged for 20 min followed by a whole-body scan. Frozen kidney sections were stained for podocytes and CD206 using immunofluorescence. Molecular imaging of diabetic db/db mice (4.9 wk, n = 6; 7.3 wk, n = 4; 13.3 wk, n = 6) and nondiabetic db/m mice (n = 6) was performed with fluorescence-labeled (99m)Tc-tilmanocept (18.5 MBq, 2.6 nmol). Thirty minutes after injection, blood, liver, kidneys, and urine were assayed for radioactivity. Renal time–activity curves were generated. Results: Rat PET whole-body images and time–activity curves of (68)Ga-IRDye800-tilmanocept demonstrated receptor-mediated renal accumulation with evidence of glomerular uptake. Activity within the renal cortex persisted during the 40-min study. Histologic examination demonstrated colocalization of CD206 and IRDye800-tilmanocept within the glomerulus. The glomerular accumulation of the coinjection and the negative control studies were significantly less than the CD206-targeted agent. The db/db mice displayed a multiphasic renal time–activity curve with high urinary bladder accumulation; the nondiabetic mice exhibited renal uptake curves dominated by a single phase with low bladder accumulation. Conclusion: This study demonstrated receptor-mediated binding to the glomerular mesangial cells and kinetic sensitivity of tilmanocept to chronic renal disease. Given the role of mesangial cells during the progression of diabetic nephropathy, PET or SPECT renal imaging with radiolabeled tilmanocept may provide a noninvasive quantitative assessment of glomerular function.

The control of the highly invasive zebra mussel (Dreissena polymorpha) has been flagged as a priority but success has been variable. A better understanding of the growth and drivers of settlement of zebra mussel is necessary for a more efficient management of this invasive species, but seasonal data are still relatively scant. We monitored the seasonal changes in settlement rates, density, and growth of zebra mussel in artificial substrates over one year in Cardiff Bay (UK), an artificial amenity lake invaded by zebra mussels in 2003 and where the species is rapidly expanding. Mean settling rates varied from 4,200 to 6,200 mussel m-2 over June to September mirroring changes in water temperature, and peaked at 17,960 mussels m-2, the highest density reported in Britain. Density was highest at the deepest panels (3 m). Growth varied significantly among sampling stations, with growth taking place during the summer and ceasing during winter and spring. Mixture analysis reveals the existence of multiple cohorts displaying different growth and settling rates and that follow different density dependent mechanisms, being positive density-dependent at low densities, and negative density-dependent at high densities. We suggest this creates the conditions necessary for source and sink metapopulations to develop which may need to be taken into account in management. Targeting mussels for removal in deep waters during the summer and early autumn might prove beneficial, but the existence of contrasting density-dependent mechanisms suggests that removal may be beneficial or counterproductive depending on local conditions.

Blood-brain barrier (BBB) disruption and subsequent neuro-inflammation occur following traumatic brain injury (TBI), resulting in a spectrum of human nervous system disorders. [Age-matched mice were divided into three groups: 5-days post TBI (n = 4), and 5-days post sham (n = 4), and naïve controls (n = 4). IRDye800CW-labeled [In vivo nuclear imaging, ex vivo fluorescence imaging, ex vivo gamma well counting, and histo-microscopy demonstrated enhanced tilmanocept uptake in the TBI region. The normalized [[

Increasing mortality from opioid overdoses has prompted increased focus on prescribing practices of physicians. Unfortunately, resident physicians rarely receive formal education in effective opioid prescribing practices or postoperative pain management. Data to inform surgical training programs regarding the utility and feasibility of formal training are lacking.Following Institutional Review Board approval, a single institution's resident physicians who had completed at least one surgical rotation were surveyed to assess knowledge of pain management and evaluate opioid prescribing practices.Fifty-three respondents (68% males and 32% females) completed the survey. Most respondents denied receiving formal instruction in opioid pain medication prescribing practices during either medical school (62.3%) or residency (56.6%); however, nearly all respondents stated they were aware of the side effects of opioid pain medications, and a majority felt confident in their knowledge of opioid pharmacokinetics and pharmacodynamics. Of the respondents, 47% either "agreed" or "strongly agreed" that they prescribed more opioid medications than necessary to patients being discharged following a surgical procedure. Individual case scenario responses demonstrated variability in the number of morphine milligram equivalents prescribed across scenarios (P 0.001). Male and nonsurgical specialty respondents reported prescribing significantly fewer overall morphine milligram equivalents in these scenarios.This pilot study shows wide variability in opioid prescribing practices and attitudes toward pain management among surgical trainees, illustrating the potential utility of formal education in pain management and effective prescribing of these medications. A broader assessment of surgical trainees' knowledge and perception of opioid prescribing practices is warranted to facilitate the development of such a program.

AIMS The microbial diversity of backyard compost piles is poorly understood compared to large-scale, highly regulated composting systems. The purpose of this study was the identification of the microbial community composition and associated change over time among three different backyard composting styles. METHODS AND RESULTS Food waste was composted in a household backyard compost bin, a small-scale aerated windrow or a semi-aerated static pile. Samples were obtained from each sequential phase of the composting process for 16s rRNA sequencing and relationships between temperature, moisture and microbial communities were examined. The Bacilli dominated in the early phases of composting then transitioned to Proteobacteria in the later stages. Different bacterial species increased and decreased dramatically in different composting systems and at different phases of the composting process. We performed qPCR to quantify gene abundance of nirS to profile the nitrogen-metabolizing bacteria present in each composting system. Gene abundance of nirS varied with temperature, but peaked during the cooling phase in the aerated windrow. CONCLUSIONS Although the phases of decomposition were not as distinct as large-scale regulated piles, the microbial diversity mirrored the appropriate phases. Interestingly, different backyard composting styles were marked by the predominance of certain bacterial species. In particular, nitrogen-metabolizing bacterial communities peaked in the later stages of decomposition. SIGNIFICANCE AND IMPACT OF THE STUDY A profile of the compost microbiome yields important clues about how differences in backyard food waste composting systems influence bacterial species that may facilitate or hinder nitrogen metabolism.

Many aspects of life involve sensitive photodetection, which is now widely implemented in solid-state devices made from semiconductor materials due to their relatively low cost, high scalability, and better compatibility with the existing CMOS technology. State-of-the-art Geiger-mode avalanche detectors and the challenges they faced in single-photon detection efficiency and timing resolution are covered. Emerging classes of solid-state detectors are then reviewed, including bandgap engineering and the use of a heavily doped emitter. A novel class of detector is introduced exhibiting monolithic incorporation of impact ionization and bipolar gain in a single device structure by using bandgap engineering. Finally, we discuss a recent detector concept which involves using disorder in solid-state material to substantially increase the probability of carrier excitation and reduce noise. The recent breakthroughs in solid-state photodetection can significantly impact areas of quantum information processing, optic communications, and imaging.

We implemented a flipped classroom curriculum for our institution’s resident physicians entering their internship year. This curriculum included instructional videos on ACLS, supplemental oxygen delivery, trans-thoracic echocardiography, and line placement, followed by a 3-day simulation-based curriculum. Overall self-efficacy of interns increased following the curriculum. This increased self-efficacy, particularly in procedural ability, was similar to that of PGY-2 residents who had 1 year of experience. Our work suggests that a flipped classroom/simulation-based curriculum for interns can effectively teach a clinical skill set in a short period, yielding self-efficacy in implementing that skill set, particularly in procedural ability, comparable to that after 1 year of residency.

The primary objective was to test the ability of a laparoscopic camera system to detect the fluorescent signal emanating from sentinel lymph nodes (SLNs) approximately 2 d after injection and imaging of a positron-emitting molecular imaging agent into the submucosa of the porcine urinary bladder. Methods: Three female pigs underwent a submucosal injection of the bladder with fluorescent-tagged tilmanocept, radiolabeled with both (68)Ga and (99m)Tc. One hour after injection, a pelvic PET/CT scan was acquired for preoperative SLN mapping. Approximately 36 h later, robotic SLN mapping was performed using a fluorescence-capable camera system. After identification of the fluorescent lymph nodes, a pelvic lymph node dissection was completed with robotic assistance. All excised nodal packets (n = 36) were assayed for (99m)Tc activity, which established a lymph node as an SLN. (99m)Tc activity was also used to calculate the amount of dye within each lymph node. Results: All of the SLNs defined by the ex vivo γ-well assay of (99m)Tc activity were detected by fluorescence mode imaging. The time between injection and robotic SLN mapping ranged from 32 to 38 h. A total of 5 fluorescent lymph nodes were detected; 2 pigs had 2 fluorescent lymph nodes and 1 pig exhibited a single lymph node. Four of the 5 SLNs exhibited increased SUVs of 12.4–139.0 obtained from PET/CT. The dye content of the injection sites ranged from 371 to 1,441 pmol, which represented 16.5%–64.1% of the injected dose; the amount of dye within the SLNs ranged from 8.5 to 88 pmol, which was equivalent to 0.38%–3.91% of the administered dose. Conclusion: Fluorescent-labeled (68)Ga-tilmanocept allows for PET imaging and real-time intraoperative detection of SLNs during robotic surgery.

The control of the highly invasive zebra mussel (Dreissena polymorpha) has been flagged as a priority but success has been variable. A better understanding of the growth and drivers of settlement of zebra mussel is necessary for a more efficient management of this invasive species, but seasonal data are still relatively scant. We monitored the seasonal changes in settlement rates, density, and growth of zebra mussel in artificial substrates over one year in Cardiff Bay (UK), an artificial amenity lake invaded by zebra mussels in 2003 and where the species is rapidly expanding. Mean settling rates varied from 4,200 to 6,200 mussel m−2over June to September mirroring changes in water temperature, and peaked at 17,960 mussels m−2, the highest density reported in Britain. Density was highest at the deepest panels (3 m). Growth varied significantly among sampling stations, with growth taking place during the summer and ceasing during winter and spring. Mixture analysis reveals the existence of multiple cohorts displaying different growth and settling rates and that follow different density dependent mechanisms, being positive density-dependent at low densities, and negative density-dependent at high densities. We suggest this creates the conditions necessary for source and sink metapopulations to develop which may need to be taken into account in management. Targeting mussels for removal in deep waters during the summer and early autumn might prove beneficial, but the existence of contrasting density-dependent mechanisms suggests that removal may be beneficial or counterproductive depending on local conditions.

Invasion facilitation, whereby one species has a positive effect on the establishment of another species, could help explain the rapid colonisation shown by some freshwater invasive species, but the underlying mechanisms remain unclear. We employed two-choice test arenas to test whether the presence of zebra mussel (Dreissena polymorpha) could facilitate the establishment of the killer shrimp (Dikerogammarus villosus). Killer shrimp preferred to settle on mats of zebra mussel, but this was unrelated to mat size, and was not different from attraction shown to artificial grass, suggesting that zebra mussel primarily provides substrate and refuge to the killer shrimp. Killer shrimp were strongly attracted to water scented by zebra mussel, but not to water scented by fish. Chemical attraction to the zebra mussel’s scent did not differ between sympatric and allopatric populations of killer shrimp, suggesting that chemical attraction is not an acquired or learned trait. Our study shows, for the first time, chemical attraction between two highly invasive freshwater species, thereby providing a plausible mechanism for invasion facilitation. This has implications for managing the spread of killer shrimp, and perhaps other freshwater invasive species, because chemical attraction could significantly increase establishment success in mutualistic systems. Failure to consider invasion facilitation may underestimate the risk of establishment, and likely also the impact of some aquatic invaders.

Invasion facilitation, whereby one species has a positive effect on the establishment of another species, could help explain the rapid colonisation shown by some freshwater invasive species, but the underlying mechanisms remain unclear. We employed two-choice test arenas to test whether the presence of zebra mussel (Dreissena polymorpha) could facilitate the establishment of the killer shrimp (Dikerogammarus villosus). Killer shrimp preferred to settle on mats of zebra mussel, but this was unrelated to mat size, and was not different from attraction shown to artificial grass, suggesting that zebra mussel primarily provides substrate and refuge to the killer shrimp. Killer shrimp were strongly attracted to water scented by zebra mussel, but not to water scented by fish. Chemical attraction to the zebra mussel’s scent did not differ between sympatric and allopatric populations of killer shrimp, suggesting that chemical facilitation is not an acquired or learned trait. Our results have implications for managing the spread of killer shrimp, and perhaps other freshwater invasive species, because invasion facilitation could significantly increase establishment success. Failure to consider invasion facilitation may underestimate the risk of establishment and likely impact of some aquatic invaders.

Thoracic aortic disease has a variety of presentations and acuities requiring meticulous planning for intervention. Patients typically present with a wide variety of comorbidities and preoperative states.

Several aspects of medical training may contribute to the ultimate goal of producing excellent physicians whose patients will have the best possible outcomes. However, the relative importance of education, evaluation and feedback, duty hours, practice structure, and program culture in achieving this goal is unclear. This study assessed associations among in-training exam performance, Accreditation Council for Graduate Medical Education (ACGME) Resident Survey responses, and American Board of Medical Specialties (ABMS) national board exam performance. Residency training programs at a university teaching hospital were classified as having 5-year first-time ABMS pass rates above (n=12) or below (n=3) the national average for their specialty. These groups were compared by ACGME Resident Survey data and in-training exam performance. Surveys were collected from 484/543 eligible residents (89%), including 177 surveys from programs with below-average board pass rates and 307 surveys from programs with aboveaverage board pass rates. In-training exam performance was similar between groups. Aboveaverage programs had stronger agreement with statements that their culture reinforced patient safety (4.72 vs. 4.30, p=0.006) and that information was not lost during transitions of care (4.14 vs. 3.63, p=0.001). Although the occurrence of interprofessional teamwork was similar between groups, above-average programs had stronger agreement with the statement that interprofessional teamwork was effective (4.60 vs. 4.17, p=0.003). Residency programs emphasizing patient safety and effective interprofessional teamwork had above-average first-time national board pass rates.

Quantitative objective measures to determine fusion achievement further enable the comparison of new technologies, such as interbody cage surface enhancement. Our aims were to compare in vivo biomechanical responses of ovine L4/5 lumbar motion segments with two cages: 1) Polyetheretherketone or 2) Polyetheretherketone with a nanosurfaced titanium porous scaffold from Nanovis, Inc.Fourteen Merino sheep randomly received either 1) standard Polyetheretherketone cage or 2) Nanocoated Polyetheretherketone cage at L4/L5 with autologous bone graft. At baseline and one-year follow-up, dynamic spinal stiffness was quantified in vivo using a validated mechanical assessment at 2 Hz, 6 Hz, and 12 Hz. The dorsoventral secant stiffness (kBoth implants increased spinal stiffness at 2 Hz (21 and 39%, respectively, p .005), and at 6 Hz (12 and 27%, p .0001). Significantly greater spinal stiffness was observed with Nanocoated Polyetheretherketone at one-year for both frequencies (p .05). No significant differences were observed at 12 Hz within or between groups. L4-L5 dorsoventral accelerations were significantly decreased one year following cage placement only with Nanocoated Polyetheretherketone (p .05) and greater reductions in acceleration were observed with Nanocoated Polyetheretherketone compared to standard Polyetheretherketone (p .05).Both cages increased spinal stiffness, yet, nanosurfaced cages resulted in greater spinal stiffness changes and decreases in L4-L5 accelerations. These findings may assist in clinical decision making and post-operative recovery strategies.

Molecular imaging with a fluorescent version of Tilmanocept may permit an accurate and facile detection of sentinel nodes of endometrial cancer. Tilmanocept accumulates in sentinel lymph nodes (SLN) by binding to a cell surface receptor unique to macrophages and dendritic cells. Four female Yorkshire pigs underwent cervical stromal injection of IRDye800-Tilmanocept, a molecular imaging agent tagged with near-infrared fluorescent dye and radiolabeled with gallium-68 and technetium-99m. PET/CT scans 1.5 hours post-injection provided pre-operative SLN mapping. Robotic-assisted lymphadenectomy was performed two days after injection, using the FireFly imaging system to identify nodes demonstrating fluorescent signal. After removal of fluorescent nodes, pelvic and periaortic node dissections were performed. Nodes were assayed for technetium-99m activity, and SLNs were established using the "10%-rule", requiring that the radioactivity of additional SLNs be greater than 10% of the "hottest" SLN. Thirty-four nodal samples were assayed ex vivo for radioactivity. All the SLNs satisfying the "10%-rule" were detected using the FireFly system. Five fluorescent nodes were detected, corresponding with preoperative PET/CT scan. Three pigs had one SLN and one pig had two SLNs, with 100% concordance between fluorescence and radioactivity. Fluorescent-labeled Tilmanocept permits real-time intraoperative detection of SLNs during robotic-assisted lymphadenectomy for endometrial cancer in a porcine model. When radiolabeled with gallium-68, Tilmanocept allows for preoperative localization of SLNs using PET/CT, and shows specificity to SLNs with persistent fluorescent signal, detectable using the FireFly system, for two days post-injection. In conclusion, these findings suggest that a phase I trial in human subjects is warranted, and that a long-term goal of an intra-operative administration of non-radioactive fluorescent-labeled Tilmanocept is possible.

Among all congenital heart disease, Ebstein anomaly is the lesion with the widest spectrum of presentation. It can present as early as the neonatal period where immediate intervention is often needed to the adult with no discernable symptoms. It is also one where overall outcome greatly relates to age at presentation. Generally, presentation in the neonatal period is associated with poor outcomes while presentation beyond the neonatal period has excellent outcomes with low operative mortality. It is thus apparent that understanding every aspect of the anatomy and physiology of Ebstein anomaly and how it manifests clinically is paramount to successful treatment. The purpose of this review is to outline the current concepts and strategies in the surgical management of Ebstein anomaly, and to discuss the current expert consensus on how best to tackle this congenital heart disease at different ages of diagnosis.

Purpose Despite a donor shortage, transplantation of lungs from donors identified as Public Health Service (PHS) Increased Risk Donors (IRDs) remains controversial, representing a potential bridge to this supply gap. While these donors are seronegative for HIV , Hepatitis B, and Hepatitis C, they have factors that place them at increased risk. Prior work has shown that the use of IRDs for lung transplantation does not result in worse survival; however, an updated definition of IRD from the PHS in 2013 has led to greater percentages of IRD classification. Methods The UNOS Standard Transplant Analysis and Research database was queried for adult lung transplantations performed between June 2013 through March 2017. Kaplan-Meier analysis compared survival of recipients receiving IRD lungs versus non-IRD lungs. A multivariate logistic regression model was then constructed to control for donor and recipient factors significant on univariate analysis . Results In the examined period, 7254 lung transplantations were performed, 1471 (20.3%) of which were from IRD, a more than two-fold increase from the years prior to the definition change (Table). IRD and non-IRD cohorts differed significantly in terms of donor age, gender, race, and cause of death, as well as recipient gender and diagnosis. Unadjusted 1-year and 3-year survival was 87.6% and 67.8% for the IRD cohort vs. 88.5% and 70.1% for the non-IRD cohort (Figure, log-rank p=0.0268). When controlling for other donor and recipient factors, IRD status was not an independent predictor of mortality (OR 1.055, 95% CI 0.91-1.22; p=0.47). Conclusion Since 2013, the relative percentage of IRD has increased dramatically, relating to the inclusion of Hepatitis C in the definition. Despite several important differences between cohorts, IRD status itself does not confer a mortality disadvantage and in the era of treatability and cure in most instances for Hepatitis C, the practice of avoiding these donors is outdated.

The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium-free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys–Gly–Lys–Arg–Lys) tumor-targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor-specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor-targeted multimodal imaging including near-infrared, time-gated, and two-photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe.

While silicon single-photon avalanche diodes (SPAD) have reached very high detection efficiency and timing resolution, their use in fibre-optic communications, optical free space communications, and infrared sensing and imaging remains limited. III-V compounds including InGaAs and InP are the prevalent materials for 1550 nm light detection. However, even the most sensitive 1550 nm photoreceivers in optical communication have a sensitivity limit of a few hundred photons. Today, the only viable approach to achieve single-photon sensitivity at 1550 nm wavelength from semiconductor devices is to operate the avalanche detectors in Geiger mode, essentially trading dynamic range and speed for sensitivity. As material properties limit the performance of Ge and III-V detectors, new conceptual insight with regard to novel quenching and gain mechanisms could potentially address the performance limitations of III-V SPADs. Novel designs that utilise internal self-quenching and negative feedback can be used to harness the sensitivity of single-photon detectors,while drastically reducing the device complexity and increasing the level of integration. Incorporation of multiple gain mechanisms, together with self-quenching and built-in negative feedback, into a single device also hold promise for a new type of detector with single-photon sensitivity and large dynamic range.

OBJECTIVE The Ages and Stages Questionnaire (ASQ) and Modified Checklist for Autism in Toddlers (M-CHAT) are commonly used screening tools for developmental delay and autism, respectively. This study aimed to evaluate the effectiveness of implementing 18-month developmental and autism screening by mail, with a standardized follow-up process for abnormal screen results. METHODS Within a prospective cohort study design, parents of 892 children received by mail the 18-month ASQ and M-CHAT questionnaires between December 2008 and September 2009. A registered nurse scored the questionnaires and, if needed, administered follow-up screening or set up a referral to Early Intervention or subspecialty pediatrics. Medical record reviews determined clinical outcomes of children who required intervention after initial screening through September 2010. Additionally, demographic factors were evaluated for association with responding to the questionnaires. RESULTS The ASQ and M-CHAT questionnaires were returned by 529 (59.3%) of the parents. Parents of White children (390/575 [67.8%]) and those with private insurance (457/660 [69.2%]) were significantly more likely to return screening questionnaires than parents of non-White (64/171 [37.4%]; P < .001) and government-insured children (58/169 [34.3%]; P < .001), respectively. Of the 529 children with returned surveys, 109 (20.6%) did not pass at least 1 of the initial screens and 12 (2.3%) were referred after not passing the follow-up screening process. CONCLUSIONS Developmental and autism screening by mail is not a sufficient method to comprehensively screen a general pediatric population. A nurse-completed, standardized follow-up process after an initial failed developmental screen may increase the yield of appropriate Early Intervention or subspecialty referrals.

PurposeTo summarize data on computed tomographic (CT) radiation doses collected from consecutive CT examinations performed at 12 facilities that can contribute to the creation of reference levels.Materials and methodsThe study was approved by the institutional review boards of the collaborating institutions and was compliant with HIPAA. Radiation dose metrics were prospectively and electronically collected from 199 656 consecutive CT examinations in 83 181 adults and 3871 consecutive CT examinations in 2609 children at the five University of California medical centers during 2013. The median volume CT dose index (CTDIvol), dose-length product (DLP), and effective dose, along with the interquartile range (IQR), were calculated separately for adults and children and stratified according to anatomic region. Distributions for DLP and effective dose are reported for single-phase examinations, multiphase examinations, and all examinations.ResultsFor adults, the median CTDIvol was 50 mGy (IQR, 37-62 mGy) for the head, 12 mGy (IQR, 7-17 mGy) for the chest, and 12 mGy (IQR, 8-17 mGy) for the abdomen. The median DLPs for single-phase, multiphase, and all examinations, respectively, were as follows: head, 880 mGy · cm (IQR, 640-1120 mGy · cm), 1550 mGy · cm (IQR, 1150-2130 mGy · cm), and 960 mGy · cm (IQR, 690-1300 mGy · cm); chest, 420 mGy · cm (IQR, 260-610 mGy · cm), 880 mGy · cm (IQR, 570-1430 mGy · cm), and 550 mGy · cm (IQR 320-830 mGy · cm); and abdomen, 580 mGy · cm (IQR, 360-860 mGy · cm), 1220 mGy · cm (IQR, 850-1790 mGy · cm), and 960 mGy · cm (IQR, 600-1460 mGy · cm). Median effective doses for single-phase, multiphase, and all examinations, respectively, were as follows: head, 2 mSv (IQR, 1-3 mSv), 4 mSv (IQR, 3-8 mSv), and 2 mSv (IQR, 2-3 mSv); chest, 9 mSv (IQR, 5-13 mSv), 18 mSv (IQR, 12-29 mSv), and 11 mSv (IQR, 6-18 mSv); and abdomen, 10 mSv (IQR, 6-16 mSv), 22 mSv (IQR, 15-32 mSv), and 17 mSv (IQR, 11-26 mSv). In general, values for children were approximately 50% those for adults in the head and 25% those for adults in the chest and abdomen.ConclusionThese summary dose data provide a starting point for institutional evaluation of CT radiation doses.

In this Communication, we describe an enzyme-responsive, paclitaxel-loaded nanoparticle and assess its safety and efficacy in vivo in a human fibrosarcoma murine xenograft. The material was generated via graft-through block copolymerization of norbornene monomers with hydrophilic targeting peptides together with hydrophobic paclitaxel prodrugs. This work represents a proof-of-concept study demonstrating the utility of enzyme-responsive nanoscale drug carriers capable of targeted accumulation and retention in tumor tissue in response to overexpressed endogenous enzymes. Critically, we observed low systemic toxicity in healthy mice following intravenous administration, with the maximum tolerated dose (MTD) exceeding 240 mg/kg with respect to paclitaxel. Furthermore, we observed efficacy against tumorigenesis paralleling that of paclitaxel at equivalent intravenous dosing, and near complete tumor growth suppression when administered intratumorally. This work represents a significant departure from traditional targeted drug delivery systems and presents a new avenue of exploration for nanomedicine.

The development of new medicines holds particular fascination for chemistry, biochemistry, and biology students interested in a career in medicine or the life sciences. The identification and refinement of lead compounds to treat diseases requires researchers to be facile in a number of different disciplines including organic synthesis, biochemistry, cell biology, and molecular biology. We have developed an interdisciplinary, inquiry-based laboratory spanning both organic chemistry and biochemistry classes that acquaints students with research in medicinal chemistry. The first part of the exercise takes place in the second semester of organic chemistry, where pairs of students design and execute their own multistep synthesis of a novel compound with anti-inflammatory and/or antimalarial potential. Later, in first semester biochemistry, many of the same students then test these synthesized compounds for cytotoxicity, inhibition of the enzyme nitric oxide synthase, and inhibition of the transcription factor NF-kB. Learning outcomes, measured by the Classroom Undergraduate Research Experience (CURE) survey, suggest that students participating in both classes had higher gains than an average student. © 2018 International Union of Biochemistry and Molecular Biology, 46(5):424-434, 2018.

Cycling excitation process (CEP) is a signal amplification mechanism showing high gain, low noise at low operation bias1,2. Depending on Auger excitation that involves localized states, CEP effect may be prominent in amorphous silicon, which has abundant localized states as a disordered material. Here we present a carbon-doped amorphous Si photodiode with ultra-high gain-bandwidth product with exceedingly low excess noise factor.

Importance Radiation doses for computed tomography (CT) vary substantially across institutions. Objective To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. Design, Setting, and Participants In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. Main Outcomes and Measures We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Results Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After the audit and meeting, head CT doses varied less, although some institutions increased and some decreased mean head CT doses and the proportion above benchmarks. Conclusions and Relevance Reviewing institutional doses and sharing dose-optimization best practices resulted in lower radiation doses for chest and abdominal CT and more consistent doses for head CT.

Recently we discovered a signal amplification mechanism to amplify photocurrent with high efficiency and low noise. Unlike conventional impact ionization used in avalanche photodetectors, the new amplification mechanism can produce high (>1000) gain with very low excess noise factor (

Purpose To determine patient, vendor, and institutional factors that influence computed tomography (CT) radiation dose. Materials and Methods The relevant institutional review boards approved this HIPAA-compliant study, with waiver of informed consent. Volume CT dose index (CTDIvol) and effective dose in 274 124 head, chest, and abdominal CT examinations performed in adult patients at 12 facilities in 2013 were collected prospectively. Patient, vendor, and institutional characteristics that could be used to predict (a) median dose by using linear regression after log transformation of doses and (b) high-dose examinations (top 25% of dose within anatomic strata) by using modified Poisson regression were assessed. Results There was wide variation in dose within and across medical centers. For chest CTDIvol, overall median dose across all institutions was 11 mGy, and institutional median dose was 7-16 mGy. Models including patient, vendor, and institutional factors were good for prediction of median doses (R2 = 0.31-0.61). The specific institution where the examination was performed (reflecting the specific protocols used) accounted for a moderate to large proportion of dose variation. For chest CTDIvol, unadjusted median CTDIvol was 16.5 mGy at one institution and 6.7 mGy at another (adjusted relative median dose, 2.6 mGy [95% confidence interval: 2.5, 2.7]). Several variables were important predictors that a patient would undergo high-dose CT. These included patient size, the specific institution where CT was performed, and the use of multiphase scanning. For example, while 49% of patients (21 411 of 43 696) who underwent multiphase abdominal CT had a high-dose examination, 8% of patients (4977 of 62 212) who underwent single-phase CT had a high-dose examination (adjusted relative risk, 6.20 [95% CI: 6.17, 6.23]). If all patients had been examined with single-phase CT, 69% (18 208 of 26 388) of high-dose examinations would have been eliminated. Patient size, institutional-specific protocols, and multiphase scanning were the most important predictors of dose (change in R2 = 8%-32%), followed by manufacturer and iterative reconstruction (change in R2, 0.2%-15.0%). Conclusion CT doses vary considerably within and across facilities. The primary factors that influenced dose variation were multiphase scanning and institutional protocol choices. It is unknown if the variation in these factors influenced diagnostic accuracy. © RSNA, 2016.

Background Dendritic cells (DC) are localized in close proximity to cancer cells in many well-known tumors, and thus maybe a useful target for tumor margin assessment. Materials and methods [ 99m Tc]- cyanine 7 (Cy7)-tilmanocept was synthesized and in vitro binding assays to bone marrow-derived DC were performed. Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma tumors, were administered 1.0 nmol of [ 99m Tc]-Cy7-tilmanocept via tail vein injection. After fluorescence imaging 1 or 2 h after injection, the tumor, muscle, and blood were assayed for radioactivity to calculate percent-injected dose. Digital images of the tumors after immunohistochemical staining for DC were analyzed to determine DC density. Results In vitro binding demonstrated subnanomolar affinity of [ 99m Tc]-Cy7-tilmanocept to DC (K A = 0.31 ± 0.11 nM). After administration of [ 99m Tc]-Cy7-tilmanocept, fluorescence imaging showed a 5.5-fold increase in tumor signal as compared with preinjection images and a 3.3-fold difference in fluorescence activity when comparing the tumor with the surgical bed after tumor excision. Immunohistochemical staining analysis demonstrated that DC density positively correlated with tumor percent of injected dose per gram ( r = 0.672, P = 0.03), and higher DC density was observed at the periphery versus center of the tumor (186 ± 54 K versus 64 ± 16 K arbitrary units, P = 0.001). Conclusions [ 99m Tc]-Cy7-tilmanocept exhibits in vitro and in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.

BACKGROUND Transanal endoscopic microsurgery is used in the surgical management of advanced rectal polyps and early rectal cancers. There are case reports of transanal endoscopic microsurgery colorectal anastomoses being performed with laparoscopic assistance in humans. METHODS The concept of a transanal endoscopic microsurgery colorectal anastomosis without laparoscopic assistance has been discussed and trialed on animal and cadaveric specimens; however, to date, there have been no technical reports of this particular procedure in the literature. RESULTS We present a technical note describing a transanal endoscopic microsurgery intraperitoneal colorectal anastomosis in a live human without laparoscopic assistance.