197 results on '"Andrew Ryan"'
Search Results
2. Pharmacological Treatment of Disinhibition in Acquired Brain Injury
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Grace Song, Mira Koro, Leon Berzen, Anthony Tung, Andrew Ryan, and Joseph Chun Wearn Tham
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Psychiatry and Mental health ,Pharmacology (medical) - Published
- 2023
3. Comparative Safety of Sleeve Gastrectomy and Gastric Bypass up to 5 Years After Surgery in Patients With Medicaid
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Ryan, Howard, Jie, Yang, Jyothi, Thumma, Anne, Ehlers, Sean, O'Neill, David, Arterburn, Andrew, Ryan, Dana, Telem, and Justin B, Dimick
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Surgery - Abstract
Compare adverse outcomes up to 5 years after sleeve gastrectomy and gastric bypass in patients with Medicaid.Sleeve gastrectomy is the most common bariatric operation among patients with Medicaid, however its long-term safety in this population is unknown.Using Medicaid claims, we performed a retrospective cohort study of adult patients who underwent sleeve gastrectomy or gastric bypass from January 1, 2012 to December 31, 2018. Instrumental variables survival analysis was used to estimate the cumulative incidence and heterogeneity of outcomes up to 5 years after surgery.Among 132,788 patients with Medicaid, 84,717 (63.8%) underwent sleeve gastrectomy and 48,071 (36.2%) underwent gastric bypass. 69,225 (52.1%) patients were White, 33,833 (25.5%) were Black, and 29,730 (22.4%) were Hispanic. Compared to gastric bypass, sleeve gastrectomy was associated with a lower 5-year cumulative incidence of mortality (1.29% vs. 2.15%), complications (11.5% vs. 16.2%), hospitalization (43.7% vs. 53.7%), ED use (61.6% vs. 68.2%), and reoperation (18.5% vs. 22.8%), but a higher cumulative incidence of revision (3.3% vs. 2.0%). Compared to White patients, the magnitude of the difference between sleeve and bypass was smaller among Black patients for ED use (5-year aHR 1.01 [95% CI 0.94-1.08] vs. 0.94 [95% CI 0.88-1.00], P0.001) and Hispanic patients for reoperation (5-year aHR 0.95 [95% CI 0.86-1.05] vs. 0.76 [95% CI 0.69-0.83], P0.001).Among patients with Medicaid undergoing bariatric surgery, sleeve gastrectomy was associated with a lower risk of mortality, complications, hospitalization, ED use, and reoperations, but a higher risk of revision compared to gastric bypass. Although the difference between sleeve and bypass was generally similar among White, Black, and Hispanic patients, the magnitude of this difference was smaller among Black patients for ED use and Hispanic patients for reoperation.
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- 2022
4. Neonate personality affects early-life resource acquisition in a large social mammal
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Bawan Amin, Dómhnall J. Jennings, Alison Norman, Andrew Ryan, Vasiliki Ioannidis, Alice Magee, Hayley-Anne Haughey, Amy Haigh, and Simone Ciuti
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foraging ,juvenile ,vigilance ,Animal Science and Zoology ,temperament ,anti-predator ,Ecology, Evolution, Behavior and Systematics ,fallow deer - Abstract
Current debate in the field of animal personality revolves around whether personality is reflecting individual differences in resource allocation or acquisition. Despite the large body of literature, the proximate relationships between personality, resource allocation, and acquisition are still unclear, especially during early stages of development. Here we studied how among-individual differences in behaviour develop over the first 6 months of life, and their potential association with resource acquisition in a free-ranging population of fallow deer (Dama dama). We related proxies of neonate personality – i.e. neonate physiological (heart rate) and behavioural (latency to leave at release) anti-predator responses to human handling – to the proportion of time fawns allocated to scanning during their first summer and autumn of life. We then investigated whether there was a trade-off between scanning time and foraging time in these juveniles, and how it developed over their first 6 months of life. We found that neonates with longer latencies at capture (i.e. risk-takers) allocated less time scanning their environment, but that this relationship was only present when fawns were 3-6 months old during autumn, but not when fawns were only 1-2 months old during summer. We also found that time spent scanning was negatively related to time spent foraging – a relationship rarely tested in juveniles of large mammals - and that this relationship becomes stronger over time, as fawns gradually switch from a nutrition rich (milk) to a nutrition poor (grass) diet. Our results highlight a potential mechanistic pathway in which neonate personality may drive differences in early-life resource acquisition, through allocation, of a large social mammal.
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- 2022
5. Combined Utility of 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Predicting Prostate Biopsy Pathology
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Shakher Ramdave, Jeremy Grummet, Andrew Ryan, Richard O'Sullivan, Arveen Kalapara, Badrinath R. Konety, Zita Ballok, and Mark Frydenberg
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Prostate biopsy ,medicine.diagnostic_test ,business.industry ,Urology ,030232 urology & nephrology ,Cancer ,Magnetic resonance imaging ,medicine.disease ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Positron emission tomography ,Prostate ,030220 oncology & carcinogenesis ,Biopsy ,medicine ,Radiology, Nuclear Medicine and imaging ,Surgery ,business ,Nuclear medicine ,Multiparametric Magnetic Resonance Imaging - Abstract
Background 68Gallium-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions. Objective To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI). Design, setting, and participants This was a retrospective analysis of 200 men who underwent 68Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018. Outcome measurements and statistical analysis The primary and secondary outcomes were detection of grade group (GG) 3–5 and GG 2–5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via 68Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy. Results and limitations The median SUVmax was greater for GG 3–5 tumours (6.40, interquartile range [IQR] 4.47–11.0) than for benign and GG 1–2 tumours (3.14, IQR 2.55–3.91; p Conclusions Greater SUVmax on 68Ga-PSMA-11 PET/CT is associated with detection of GG 3–5 cancer on biopsy. The combination of PI-RADS score and SUVmax provides higher sensitivity and NPV than either alone. 68Ga-PSMA-11 PET/CT may be useful alongside mpMRI in improving risk stratification for localised disease. Patient summary The amount of a radioactive tracer taken up in the prostate during a type of scan called PET (positron emission tomography) can predict whether aggressive prostate cancer is likely to be found on biopsy. This may complement the more usual type of scan, MRI (magnetic resonance imaging), used to detect prostate cancer.
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- 2022
6. Can <scp> 68 Ga‐PSMA positron emission tomography </scp> and multiparametric <scp>MRI</scp> guide treatment for biochemical recurrence after radical prostatectomy?
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Yash Khanna, Vidyasagar Chinni, Kavitha Gnanasambantham, Richard O'Sullivan, Zita E. Ballok, Andrew Ryan, Shakher Ramdave, Dinesh Sivaratnam, Patrick Bowden, Mario Guerrieri, Weranja K.B. Ranasinghe, and Mark Frydenberg
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Urology - Published
- 2023
7. Mitochondrial electron transport chain, ceramide and Coenzyme Q are linked in a pathway that drives insulin resistance in skeletal muscle
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Alexis Diaz-Vegas, Soren Madsen, Kristen C. Cooke, Luke Carroll, Jasmine X.Y. Khor, Nigel Turner, Xin Ying Lim, Miro A. Astore, Jonathan Morris, Anthony Don, Amanda Garfield, Simona Zarini, Karin A. Zemski Berry, Andrew Ryan, Bryan C. Bergman, Joseph T. Brozinick, David E. James, and James G. Burchfield
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SummaryInsulin resistance (IR) is a complex metabolic disorder that underlies several human diseases, including type 2 diabetes and cardiovascular disease. Despite extensive research, the precise mechanisms underlying IR development remain poorly understood. Here, we provide new insights into the mechanistic connections between cellular alterations associated with IR, including increased ceramides, deficiency of coenzyme Q (CoQ), mitochondrial dysfunction, and oxidative stress. We demonstrate that elevated levels of ceramide in the mitochondria of skeletal muscle cells results in CoQ depletion and loss of mitochondrial respiratory chain components, leading to mitochondrial dysfunction and IR. Further, decreasing mitochondrial ceramide levels in vitro and in animal models increased CoQ levels and was protective against IR. CoQ supplementation also rescued ceramide-associated IR. Examination of the mitochondrial proteome from human muscle biopsies revealed a strong correlation between the respirasome system and mitochondrial ceramide as key determinants of insulin sensitivity. Our findings highlight the mitochondrial Ceramide-CoQ-respiratory chain nexus as a potential foundation of an IR pathway that may also play a critical role in other conditions associated with ceramide accumulation and mitochondrial dysfunction, such as heart failure, cancer, and aging. These insights may have important clinical implications for the development of novel therapeutic strategies for the treatment of IR and related metabolic disorders.
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- 2023
8. PD04-02 USING GENOMIC AND TRANSCRIPTOMIC PROPERTIES TO DETERMINE ANDROGEN RESPONSE IN DUCTAL PROSTATE CANCERS AND DETERMINE EFFICACY OF POLY(ADP-RIBOSE) POLYMERASE INHIBITORS WITH ANDROGEN SIGNALLING INHIBITORS THERAPY IN VITRO
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Weranja Ranasinghe, Melbourne, Australia Patricia Troncoso, Mitchell Lawrence, Nicholas Choo, Birunthi Niranjan, Melissa Papargiris, Hong Wang, Andrew Ryan, Peter Shepherd, Bradley Broom, Ganiraju Manyam, Renea Taylor, Timothy Thompson, Nora Navone, Gail Risbridger, and Brian Chapin
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Urology - Published
- 2023
9. Mouse strain-dependent variation in metabolic associated fatty liver disease (MAFLD): a comprehensive resource tool for pre-clinical studies
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Hamzeh Karimkhanloo, Stacey N. Keenan, Jacqueline Bayliss, William De Nardo, Paula M. Miotto, Camille J. Devereux, Shuai Nie, Nicholas A. Williamson, Andrew Ryan, Matthew J. Watt, and Magdalene K. Montgomery
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Multidisciplinary - Abstract
Non-alcoholic steatohepatitis (NASH), characterized as the joint presence of steatosis, hepatocellular ballooning and lobular inflammation, and liver fibrosis are strong contributors to liver-related and overall mortality. Despite the high global prevalence of NASH and the substantial healthcare burden, there are currently no FDA-approved therapies for preventing or reversing NASH and/or liver fibrosis. Importantly, despite nearly 200 pharmacotherapies in different phases of pre-clinical and clinical assessment, most therapeutic approaches that succeed from pre-clinical rodent models to the clinical stage fail in subsequent Phase I-III trials. In this respect, one major weakness is the lack of adequate mouse models of NASH that also show metabolic comorbidities commonly observed in NASH patients, including obesity, type 2 diabetes and dyslipidaemia. This study provides an in-depth comparison of NASH pathology and deep metabolic profiling in eight common inbred mouse strains (A/J, BALB/c, C3H/HeJ, C57BL/6J, CBA/CaH, DBA/2J, FVB/N and NOD/ShiLtJ) fed a western-style diet enriched in fat, sucrose, fructose and cholesterol for eight months. Combined analysis of histopathology and hepatic lipid metabolism, as well as measures of obesity, glycaemic control and insulin sensitivity, dyslipidaemia, adipose tissue lipolysis, systemic inflammation and whole-body energy metabolism points to the FVB/N mouse strain as the most adequate diet-induced mouse model for the recapitulation of metabolic (dysfunction) associated fatty liver disease (MAFLD) and NASH. With efforts in the pharmaceutical industry now focussed on developing multi-faceted therapies; that is, therapies that improve NASH and/or liver fibrosis, and concomitantly treat other metabolic comorbidities, this mouse model is ideally suited for such pre-clinical use.
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- 2023
10. 68 Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer
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Zita E. Ballok, Dinesh Sivaratnam, Jeremy Grummet, Andrew Ryan, Shakher Ramdave, Alan L. Xue, Richard O'Sullivan, Sidney M. Levy, Arveen Kalapara, Daniel Moon, and Mark Frydenberg
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education.field_of_study ,medicine.diagnostic_test ,business.industry ,Urology ,Population ,Standardized uptake value ,medicine.disease ,Gleason pattern ,Prostate cancer ,Positron emission tomography ,Biopsy ,Glutamate carboxypeptidase II ,Medicine ,business ,education ,Nuclear medicine ,Pathological - Abstract
Purpose Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (68Ga-PSMA PET/CT) and the maximum Standardized Uptake Value (SUVmax) may improve risk stratification within this population. Materials and methods We reviewed men with ISUP Grade Group 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per-segment at surgery, at three thresholds: >/ / / Results Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/ / / 50% (OR=1.39 [95%CI 1.18-1.65], p 20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathologic upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value (PPV) 75% and negative predictive value (NPV) 72%. Threshold 5.4 predicted pathologic upgrading with 91% specificity and NPV 94%. Conclusions SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.
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- 2022
11. Evidence-Based Opioid Prescribing Guidelines and New Persistent Opioid Use After Surgery
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Ryan Howard, Andrew Ryan, Hsou Mei Hu, Craig S. Brown, Jennifer Waljee, Mark C. Bicket, Michael Englesbe, and Chad M. Brummett
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Surgery - Published
- 2023
12. Loss of SNAI2 in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy
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Stefano Mangiola, Jeremy Grummet, Michael Kerger, Paul Ruljancich, Ryan Stuchbery, David Clarke, Justin S. Peters, Andrew Ryan, Niall M. Corcoran, Phillip Parente, Nicholas Howard, Christopher M. Hovens, Natalie Kurganovs, Sam Norden, Anthony J. Costello, Anne Ngyuen, Corrina A Grima, Patrick McCoy, Geoff Macintyre, Philip Dundee, Marek Cmero, and Ken Chow
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Male ,0301 basic medicine ,Cancer Research ,Epithelial-Mesenchymal Transition ,Antineoplastic Agents, Hormonal ,Bicalutamide ,Regulator ,Tosyl Compounds ,Androgen deprivation therapy ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Downregulation and upregulation ,Nitriles ,Humans ,Medicine ,Anilides ,Degarelix ,Aged ,business.industry ,Hormonal Therapy ,Androgen Antagonists ,ORIGINAL REPORTS ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Androgen receptor ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Androstenes ,Snail Family Transcription Factors ,business ,Oligopeptides ,Reprogramming ,Signal Transduction ,medicine.drug - Abstract
PURPOSE Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2, a key regulator of EMT reprogramming. CONCLUSION We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2, a key transcriptional regulator of EMT, correlates with clinical response.
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- 2021
13. Fine-regolith production on asteroids controlled by rock porosity
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G. Poggiali, Marco Delbo, M. A. Barucci, Benjamin Rozitis, Kevin J. Walsh, J. D. P. Deshapriya, Dante S. Lauretta, John Robert Brucato, Josh Emery, Andrew Ryan, Erik Asphaug, K. N. Burke, R. L. Ballouz, Daniella DellaGiustina, Carina Bennett, Edward A. Cloutis, William F. Bottke, C. Avdellidou, and Saverio Cambioni
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Multidisciplinary ,Meteoroid ,Asteroid ,Carbonaceous chondrite ,Breccia ,Compaction ,Geochemistry ,Porosity ,Cementation (geology) ,Regolith ,Geology - Abstract
Spacecraft missions have observed regolith blankets of unconsolidated subcentimetre particles on stony asteroids1–3. Telescopic data have suggested the presence of regolith blankets also on carbonaceous asteroids, including (101955) Bennu4 and (162173) Ryugu5. However, despite observations of processes that are capable of comminuting boulders into unconsolidated materials, such as meteoroid bombardment6,7 and thermal cracking8, Bennu and Ryugu lack extensive areas covered in subcentimetre particles7,9. Here we report an inverse correlation between the local abundance of subcentimetre particles and the porosity of rocks on Bennu. We interpret this finding to mean that accumulation of unconsolidated subcentimetre particles is frustrated where the rocks are highly porous, which appears to be most of the surface10. The highly porous rocks are compressed rather than fragmented by meteoroid impacts, consistent with laboratory experiments11,12, and thermal cracking proceeds more slowly than in denser rocks. We infer that regolith blankets are uncommon on carbonaceous asteroids, which are the most numerous type of asteroid13. By contrast, these terrains should be common on stony asteroids, which have less porous rocks and are the second-most populous group by composition13. The higher porosity of carbonaceous asteroid materials may have aided in their compaction and cementation to form breccias, which dominate the carbonaceous chondrite meteorites14. The absence of fine regolith on the asteroid Bennu is due to the high porosity of its rocks, which compress rather than fragment after impacts and exhibit slow thermal cracking.
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- 2021
14. The modified International Society of Urological Pathology system improves concordance between biopsy and prostatectomy tumour grade
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Niall M. Corcoran, Anthony J. Costello, Andrew Ryan, David M.Z.B. Hennes, James Sewell, Justin S. Peters, M Kerger, and Christopher M. Hovens
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Male ,medicine.medical_specialty ,Pathology ,Biopsy ,Urology ,Concordance ,medicine.medical_treatment ,Adenocarcinoma ,Prostate cancer ,Prostate ,medicine ,Humans ,Sampling (medicine) ,Multiparametric Magnetic Resonance Imaging ,Retrospective Studies ,Prostatectomy ,medicine.diagnostic_test ,business.industry ,Transperineal biopsy ,Prostatic Neoplasms ,Prostate-Specific Antigen ,medicine.disease ,medicine.anatomical_structure ,Histopathology ,Neoplasm Grading ,business - Abstract
OBJECTIVES: To assess the concordance between biopsy and radical prostatectomy (RP) specimens using the 2005 Gleason score (GS) and the International Society of Urological Pathology (ISUP) 2014/World Health Organization 2016 modified system, accounting for the introduction of transperineal biopsy and pre-biopsy multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: Between 2002 and 2019, we identified 2431 patients with paired biopsy and RP histopathology from a prospectively recorded and maintained prostate cancer database. Biopsy specimens were graded according to the 2005 GS or ISUP 2014 modified system, according to the year of diagnosis. Multivariable logistic regression analysis was conducted to retrospectively assess the impact of prostate-specific antigen (PSA), PSA density, age, pre-biopsy mpMRI, and biopsy method, on the rate of upgraded disease. The kappa coefficient was used to establish the degree of change in concordance between groups. RESULTS: Overall, 24% of patients had upgraded disease and 8% of patients had downgraded disease when using the modified ISUP 2014 criteria. Agreement in the updated ISUP 2014 cohort was 68%, compared with 55% in the 2005 GS group, which was validated by a kappa coefficient that was good (k = 0.5 ± 0.4) and poor (k = 0.3 ± 0.1), respectively. In multivariable models, a change in grading system independently improved overall disease concordance (P = 0.02), and there were no other co-segregated patient or pathological factors such as PSA, total number of cores, maximum cancer length, biopsy route or the use of mpMRI that impacted this finding. CONCLUSION: The 2014 ISUP modifed system improves overall concordance between biopsy and surgical specimens, and thus allows more accurate prognostication and management in high-grade disease, independent of more extensive prostate sampling and the use of mpMRI.
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- 2021
15. Focal low dose-rate brachytherapy for low to intermediate risk prostate cancer: preliminary experience at an Australian institution
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Elliot Anderson, Nathan Lawrentschuk, Lloyd M. L. Smyth, Jeremy Grummet, Richard O'Sullivan, Andrew Ryan, and Andrew W. See
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Urology ,medicine.medical_treatment ,Brachytherapy ,Retrospective cohort study ,medicine.disease ,Low-Dose Rate Brachytherapy ,Prostate cancer ,medicine.anatomical_structure ,Reproductive Medicine ,Prostate ,Interquartile range ,Biopsy ,medicine ,Original Article ,Radiology ,Intermediate Grade ,business - Abstract
BACKGROUND: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa. METHODS: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion. RESULTS: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1–31.3] and 24.2 (IQR 17.9–30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12–24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF). CONCLUSIONS: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12–18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.
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- 2021
16. The MURAL collection of prostate cancer patient-derived xenografts enables discovery through preclinical models of uro-oncology
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Melissa Papargiris, Natalie Lister, Hong Wang, Renea A. Taylor, Sam Norden, Shivakumar Keerthikumar, Andrew Ryan, Mahesh Iddawala, Michelle Richards, David L Goode, Mitchell G. Lawrence, Shomik Sengupta, Andrew Bakshi, Shahneen Sandhu, Jeremy Grummet, Laurence Harewood, John F. Ouyang, David Clouston, Heather Thorne, Luc Furic, Jeremy Goad, Rosalia Quezada Urban, Birunthi Niranjan, Nicholas Choo, Ashlee K. Clark, Carmel Pezaro, Samantha O'Dea, Daniel Moon, Declan G. Murphy, Lisa Devereux, Gail P. Risbridger, Jenna Kraska, Laura H Porter, Mark Frydenberg, Linda Teng, Rodney J. Hicks, Zhuoer Li, Heather B Madsen, David Pook, William Wheelahan, Arun Azad, John Pedersen, Roxanne Toivanen, John Kourambas, and Edmond M. Kwan
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Male ,Oncology ,Drug Evaluation, Preclinical ,General Physics and Astronomy ,Mice, SCID ,Mice ,chemistry.chemical_compound ,Prostate cancer ,Mice, Inbred NOD ,Prostate ,Cancer genomics ,Prospective Studies ,Neoplasm Metastasis ,Prospective cohort study ,Genome ,Multidisciplinary ,Organoids ,medicine.anatomical_structure ,Tissue bank ,Adenocarcinoma ,Heterografts ,medicine.medical_specialty ,Urology ,Science ,MEDLINE ,Mural ,Tissue Banks ,General Biochemistry, Genetics and Molecular Biology ,Article ,Targeted therapies ,Internal medicine ,medicine ,Animals ,Enzalutamide ,Humans ,Cancer models ,business.industry ,Cancer ,Prostatic Neoplasms ,General Chemistry ,medicine.disease ,Xenograft Model Antitumor Assays ,Clinical trial ,Disease Models, Animal ,Abiraterone ,chemistry ,Mutation ,Transcriptome ,business - Abstract
Preclinical testing is a crucial step in evaluating cancer therapeutics. We aimed to establish a significant resource of patient-derived xenografts (PDXs) of prostate cancer for rapid and systematic evaluation of candidate therapies. The PDX collection comprises 59 tumors collected from 30 patients between 2012–2020, coinciding with availability of abiraterone and enzalutamide. The PDXs represent the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumors to castration-resistant metastases. Inter- and intra-tumor heterogeneity in adenocarcinoma and neuroendocrine phenotypes is evident from bulk and single-cell RNA sequencing data. Organoids can be cultured from PDXs, providing further capabilities for preclinical studies. Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. To govern the distribution of PDXs, we formed the Melbourne Urological Research Alliance (MURAL). This PDX collection is a substantial resource, expanding the capacity to test and prioritize effective treatments for prospective clinical trials in prostate cancer., The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.
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- 2021
17. Changes in Shared Savings Program Participation After Launch of Pathways to Success
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Meiling Ying, Richard A. Hirth, Phyllis Yan, Addison Shay, Sitara Murali, Andrew Ryan, and John M. Hollingsworth
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Internal Medicine - Published
- 2022
18. Author response: Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex
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Shelly Applen Clancey, Andrew Ryan Passer, Terrance Shea, Márcia David-Palma, Anna Floyd Averette, Teun Boekhout, Betina M Porcel, Minou Nowrousian, Christina A Cuomo, Sheng Sun, Joseph Heitman, and Marco A Coelho
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- 2022
19. Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival
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Daniel Moon, Damien M Bolton, Declan G. Murphy, Laurence Harewood, Homayoun Zargar, Justin S. Peters, Uri Hanegbi, Alastair D. Lamb, Dennis King, Paul Ruljancich, Niall M. Corcoran, Dennis Gyomber, Philip Dundee, Mark Frydenberg, Ken Chow, Yee Chan, Anthony J. Costello, David R Webb, Clare Verrill, Lih-Ming Wong, Jeremy Goad, Anthony T. Papenfuss, Andrew Ryan, Marc A. Furrer, Peter Liodakis, Dinesh Agarwal, Nathan Lawrentschuk, Christopher M. Hovens, and Justin Bedő
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0301 basic medicine ,Oncology ,Biochemical recurrence ,Cancer Research ,medicine.medical_specialty ,Prostatectomy ,business.industry ,medicine.medical_treatment ,Cancer ,Salvage therapy ,Acinar adenocarcinoma ,medicine.disease ,03 medical and health sciences ,Prostate cancer ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Adenocarcinoma ,business ,Survival analysis - Abstract
Background Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. Methods Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). Results A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p Conclusions The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.
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- 2021
20. Oxytocin receptor antagonists as a novel pharmacological agent for reducing smooth muscle tone in the human prostate
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Sophie N, Lee, Jenna, Kraska, Melissa, Papargiris, Linda, Teng, Birunthi, Niranjan, Johanna, Hammar, Andrew, Ryan, Mark, Frydenberg, Nathan, Lawrentschuk, Ralf, Middendorff, Stuart J, Ellem, Michael, Whittaker, Gail P, Risbridger, and Betty, Exintaris
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Male ,Urology ,Science ,Prostate ,Prostatic Hyperplasia ,Muscle, Smooth ,Middle Aged ,Oxytocin ,Article ,Vasotocin ,Endocrinology ,Receptors, Oxytocin ,Muscle Tonus ,Humans ,Medicine ,Aged ,Cell Proliferation ,Muscle Contraction - Abstract
Pharmacotherapies for the treatment of Benign Prostatic Hyperplasia (BPH) are targeted at reducing cellular proliferation (static component) or reducing smooth muscle tone (dynamic component), but response is unpredictable and many patients fail to respond. An impediment to identifying novel pharmacotherapies is the incomplete understanding of paracrine signalling. Oxytocin has been highlighted as a potential paracrine mediator of BPH. To better understand oxytocin signalling, we investigated the effects of exogenous oxytocin on both stromal cell proliferation, and inherent spontaneous prostate contractions using primary models derived from human prostate tissue. We show that the Oxytocin Receptor (OXTR) is widely expressed in the human prostate, and co-localises to contractile cells within the prostate stroma. Exogenous oxytocin did not modulate prostatic fibroblast proliferation, but did significantly (p
- Published
- 2021
21. Link for Equity, a community-engaged waitlist randomized controlled trial of a culturally responsive trauma-informed care program for BIPOC students: Design features and characteristics of baseline sample
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Marizen R. Ramirez, Andrew Ryan, Alyson B. Harding, Tiffaney Renfro, Timothy R. Church, Christina Rosebush, Alexis Grimes Trotter, Bao Nhia Xiong, John Gonzalez, and Briana Woods-Jaeger
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Pharmacology (medical) ,General Medicine - Published
- 2023
22. Development of a New Genetic Transformation System for White and Green Ash Using Embryogenic Cultures
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Andrew Ryan Tull, Heather Gladfelter, Flavia Pampolini, Lynne Rieske, Charles Dana Nelson, and Scott Merkle
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fungi ,Forestry ,Fraxinus americana ,Fraxinus pennsylvanica ,transgenic trees ,somatic embryogenesis ,GUSi ,emerald ash borer - Abstract
All North American ash (Fraxinus spp.) species are threatened by the emerald ash borer (EAB; Agrilus planipennis), an exotic beetle which has already destroyed millions of ash trees in the U.S. and Canada. Although both chemical insecticides and biological control can be effective, and host resistance appears possible, the speed of the invasion has defied traditional management approaches. One potential, innovative approach to managing this destructive insect is to develop a host tree-induced gene silencing strategy using RNA interference (RNAi) constructs targeting EAB-specific genes. An important requirement for applying RNAi technology is a reliable transformation/regeneration system for the host tree species. We developed an Agrobacterium-mediated gene transfer system for white ash (F. americana) and green ash (F. pennsylvanica) using the embryogenic cultures of these species as target material. Embryogenic suspension cultures of multiple genotypes of both species were plated and inoculated with A. tumefaciens carrying the pFHI-GUSi expression vector, which carries the nptII selectable marker and intron-GUS reporter genes, followed by selection on a semi-solid medium containing geneticin. Putative transgenic events showed expression of the GUS gene at all tested developmental stages from callus to plantlets, and transgene presence in the leaves of regenerated plants was confirmed using PCR. The overall average transformation efficiency achieved was 14.5 transgenic events per gram of tissue. Transgenic somatic seedlings of two white ash and three green ash genotypes were produced and acclimated to greenhouse conditions.
- Published
- 2022
- Full Text
- View/download PDF
23. Obligate sexual reproduction of a homothallic fungus closely related to the
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Andrew Ryan, Passer, Shelly Applen, Clancey, Terrance, Shea, Márcia, David-Palma, Anna Floyd, Averette, Teun, Boekhout, Betina M, Porcel, Minou, Nowrousian, Christina A, Cuomo, Sheng, Sun, Joseph, Heitman, and Marco A, Coelho
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Reproduction ,Cryptococcus neoformans ,Humans ,Saccharomyces cerevisiae ,Genes, Mating Type, Fungal ,Biological Evolution - Abstract
titleeLife digest/title.Fungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved a variety of strategies to reproduce. Normally, fungi reproduce in one of two ways: either they reproduce asexually, with one individual producing a new individual identical to itself, or they reproduce sexually, with two individuals of different 'mating types' contributing to produce a new individual. However, individuals of some species exhibit 'homothallism' or self-fertility: these individuals can produce reproductive cells that are universally compatible, and therefore can reproduce sexually with themselves or with any other cell in the population.Homothallism has evolved multiple times throughout the fungal kingdom, suggesting it confers advantage when population numbers are low or mates are hard to find. Yet some homothallic fungi been overlooked compared to heterothallic species, whose mating types have been well characterised. Understanding the genetic basis of homothallism and how it evolved in different species can provide insights into pathogenic species that cause fungal disease.With that in mind, Passer, Clancey et al. explored the genetic basis of homothallism inPasser, Clancey et al. showed thatPasser, Clancey et al. also found that, unlike otherThis work offers new insights into how different modes of sexual reproduction have evolved in fungi. It also provides another interesting case of how genome plasticity and evolutionary pressures can produce similar outcomes, homothallism, via different evolutionary paths. Lastly, assembling the complete genome ofFungi are enigmatic organisms that flourish in soil, on decaying plants, or during infection of animals or plants. Growing in myriad forms, from single-celled yeast to multicellular molds and mushrooms, fungi have also evolved a variety of strategies to reproduce. Normally, fungi reproduce in one of two ways: either they reproduce asexually, with one individual producing a new individual identical to itself, or they reproduce sexually, with two individuals of different ‘mating types’ contributing to produce a new individual. However, individuals of some species exhibit ‘homothallism’ or self-fertility: these individuals can produce reproductive cells that are universally compatible, and therefore can reproduce sexually with themselves or with any other cell in the population. Homothallism has evolved multiple times throughout the fungal kingdom, suggesting it confers advantage when population numbers are low or mates are hard to find. Yet some homothallic fungi been overlooked compared to heterothallic species, whose mating types have been well characterised. Understanding the genetic basis of homothallism and how it evolved in different species can provide insights into pathogenic species that cause fungal disease. With that in mind, Passer, Clancey et al. explored the genetic basis of homothallism in
- Published
- 2022
24. Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control
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Magdalene K. Montgomery, Jacqueline Bayliss, Shuai Nie, William De Nardo, Stacey N. Keenan, Paula M. Miotto, Hamzeh Karimkhanloo, Cheng Huang, Ralf B. Schittenhelm, Anthony S. Don, Andrew Ryan, Nicholas A. Williamson, Geraldine J. Ooi, Wendy A. Brown, Paul R. Burton, Benjamin L. Parker, and Matthew J. Watt
- Subjects
Multidisciplinary ,General Physics and Astronomy ,lipids (amino acids, peptides, and proteins) ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogate hepatocyte protein secretion in two models of murine NASH to understand how liver-derived factors modulate lipid metabolism and insulin sensitivity in peripheral tissues. We reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism, and identify arylsulfatase A (ARSA) as a hepatokine that is upregulated in NASH and type 2 diabetes. Mechanistically, hepatic ARSA reduces sulfatide content and increases lysophosphatidylcholine (LPC) accumulation within lipid rafts and suppresses LPC secretion from the liver, thereby lowering circulating LPC and lysophosphatidic acid (LPA) levels. Reduced LPA is linked to improvements in skeletal muscle insulin sensitivity and systemic glycemic control. Hepatic silencing of Arsa or inactivation of ARSA’s enzymatic activity reverses these effects. Together, this study provides a unique resource describing global changes in hepatokine secretion in NASH, and identifies ARSA as a regulator of liver to muscle communication and as a potential therapeutic target for type 2 diabetes.
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- 2022
25. Motivating English Second Language Learners to Succeed in Business Writing
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Andrew, Ryan and Michael Mielke
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application/pdf
- Published
- 2020
26. Amphitheatre‐headed canyons of Southern Utah: Stratigraphic control of canyon morphology
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Andrew Ryan and Kelin X. Whipple
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Canyon ,geography ,geography.geographical_feature_category ,010504 meteorology & atmospheric sciences ,Geography, Planning and Development ,Planetary geology ,010502 geochemistry & geophysics ,01 natural sciences ,Paleontology ,Stratigraphy ,Earth and Planetary Sciences (miscellaneous) ,Erosion ,Geology ,Groundwater ,0105 earth and related environmental sciences ,Earth-Surface Processes ,Groundwater seepage - Abstract
Amphitheater-headed canyon distribution in Southern Utah is most strongly related to local stratigraphy, rather than groundwater seepage erosion.
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- 2020
27. The Philadelphia Story (1940) in 9 Frames
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Andrew Ryan Wentz, Ashley R. Pickett, Andrew P. Nielsen, Alexis Dickerson, and Ashley R. Spillane
- Abstract
The Philadelphia Story (1940) USA Director George Cukor Runtime 112 minutes Blu-ray USA, 2017 Distributed by The Criterion Collection (region A/1)
- Published
- 2020
28. Detection and localisation of primary prostate cancer using 68 gallium prostate‐specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology
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Richard O'Sullivan, Zita Ballok, Tatenda Nzenza, Arveen Kalapara, Damien M Bolton, Jeremy Grummet, Henry Y C Pan, Michael S Hofman, Shakher Ramdave, Martin H Cherk, Declan G. Murphy, Badrinath R. Konety, Nathan Lawrentschuk, Mark Frydenberg, and Andrew Ryan
- Subjects
PET-CT ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Prostatectomy ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Retrospective cohort study ,medicine.disease ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,medicine.anatomical_structure ,Positron emission tomography ,Prostate ,030220 oncology & carcinogenesis ,medicine ,business ,Prospective cohort study ,Multiparametric Magnetic Resonance Imaging - Abstract
OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.
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- 2020
29. In situ evidence of thermally induced rock breakdown widespread on Bennu’s surface
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Ronald-Louis Ballouz, C. Drouet d'Aubigny, Bashar Rizk, Carina Bennett, Humberto Campins, S. J. Martel, Daniella DellaGiustina, Erica Jawin, Andrew Ryan, Kevin J. Walsh, Stephen R. Schwartz, Maurizio Pajola, Jamie Molaro, Dante S. Lauretta, Dathon Golish, William F. Bottke, and Romy D. Hanna
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010504 meteorology & atmospheric sciences ,Science ,General Physics and Astronomy ,Weathering ,Geodynamics ,01 natural sciences ,Space weathering ,Article ,General Biochemistry, Genetics and Molecular Biology ,Astrobiology ,0103 physical sciences ,lcsh:Science ,010303 astronomy & astrophysics ,0105 earth and related environmental sciences ,Multidisciplinary ,Lead (sea ice) ,Fracture mechanics ,General Chemistry ,Regolith ,Asteroid ,Fracture (geology) ,lcsh:Q ,Asteroids, comets and Kuiper belt ,Geology - Abstract
Rock breakdown due to diurnal thermal cycling has been hypothesized to drive boulder degradation and regolith production on airless bodies. Numerous studies have invoked its importance in driving landscape evolution, yet morphological features produced by thermal fracture processes have never been definitively observed on an airless body, or any surface where other weathering mechanisms may be ruled out. The Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS-REx) mission provides an opportunity to search for evidence of thermal breakdown and assess its significance on asteroid surfaces. Here we show boulder morphologies observed on Bennu that are consistent with terrestrial observations and models of fatigue-driven exfoliation and demonstrate how crack propagation via thermal stress can lead to their development. The rate and expression of this process will vary with asteroid composition and location, influencing how different bodies evolve and their apparent relative surface ages from space weathering and cratering records., In their study, the authors discuss the potential of thermal weathering on airless bodies. As a case study, they use boulder and fracture morphologies on asteroid Bennu.
- Published
- 2020
30. Long-term comparative effectiveness of gastric bypass and sleeve gastrectomy on use of antireflux medication: a difference-in-differences analysis
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Ryan Howard, Jie Yang, Jyothi Thumma, David E. Arterburn, Andrew Ryan, Grace Chao, Dana Telem, and Justin B. Dimick
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Treatment Outcome ,Gastrectomy ,Gastric Bypass ,Gastroesophageal Reflux ,Humans ,Surgery ,Laparoscopy ,Medicare ,United States ,Aged ,Obesity, Morbid ,Retrospective Studies - Abstract
Gastroesophageal reflux (GERD) is common among patients with obesity who undergo bariatric surgery. Although gastric bypass and sleeve gastrectomy are the most common bariatric operations performed in the United States, their long-term comparative effectiveness on GERD medication use is unknown.To compare the long-term effectiveness of gastric bypass and sleeve gastrectomy on use of antireflux medication.National cohort undergoing inpatient bariatric surgery.This is a retrospective study of Medicare beneficiaries undergoing gastric bypass and sleeve gastrectomy between January 1, 2012, and December 31, 2017. A difference-in-differences analysis was conducted to evaluate the differential change in antireflux medication use between groups before and after surgery.A total of 16,640 patients underwent gastric bypass, and 26,724 patients underwent sleeve gastrectomy. Before surgery, GERD medication use was higher among patients who underwent gastric bypass (62.4%; 95% confidence interval [CI]: 62.0%-63.7%) compared with patients who underwent sleeve gastrectomy (60.1%; 95% CI: 59.3%-60.9%). Five years after surgery, GERD medication use was lower in patients who underwent gastric bypass (47.8%; 95% CI: 46.3%-49.3%) compared with patients who underwent sleeve gastrectomy (53.7%; 95% CI: 50.5%-56.9%). The differential decrease from baseline GERD medication use was greater for patients who underwent gastric bypass at 2 years (-4.1 percentage points [pp]; 95% CI: -1.7 to -6.5 pp), 3 years (-4.3 pp; 95% CI: -1.6 to -7.0 pp), 4 years (-6.9 pp; 95% CI: -4.1 to -9.6 pp), and 5 years (-8.3 pp; 95% CI: -3.7 to 12.8 pp) after surgery.Though use of antireflux medication decreased following both procedures, gastric bypass was associated with a greater reduction in antireflux medication use 5 years after surgery compared with sleeve gastrectomy. Understanding the long-term comparative effectiveness of these common bariatric operations may better inform treatment decisions among patients and surgeons.
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- 2022
31. Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients
- Author
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Talia L. Fuchs, Fiona Maclean, John Turchini, A. Cristina Vargas, Selina Bhattarai, Abbas Agaimy, Arndt Hartmann, Chia-Sui Kao, Carla Ellis, Michael Bonert, Xavier Leroy, Lakshmi P. Kunju, Lauren Schwartz, Admire Matsika, Sean R. Williamson, Priya Rao, Mukul Divatia, Rosa Guarch, Ferran Algaba, Marcelo L. Balancin, Ming Zhou, Hemamali Samaratunga, Isabela Werneck da Cunha, Fadi Brimo, Andrew Ryan, David Clouston, Manju Aron, Marie O'Donnell, Emily Chan, Michelle S. Hirsch, Holger Moch, Chun-Yin Pang, Cheuk Wah, Weihua Yin, Joanna Perry-Keene, Asli Yilmaz, Angela Chou, Adele Clarkson, Gerhard van der Westhuizen, Ella Morrison, Jonathan Zwi, Ondrej Hes, Kiril Trpkov, and Anthony J. Gill
- Subjects
Adult ,Aged, 80 and over ,Male ,Hyperplasia ,Middle Aged ,Immunohistochemistry ,Kidney Neoplasms ,Pathology and Forensic Medicine ,Succinate Dehydrogenase ,Necrosis ,Young Adult ,Humans ,Female ,Carcinoma, Renal Cell ,Aged - Abstract
Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.
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- 2022
32. Correction: Volume–outcome relationships for Roux-en-Y gastric bypass patients in the sleeve gastrectomy era
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Grace F. Chao, Jie Yang, Jyothi Thumma, Karan R. Chhabra, David E. Arterburn, Andrew Ryan, Dana A. Telem, and Justin B. Dimick
- Subjects
Surgery - Published
- 2023
33. A Difference-in-Differences Analysis of New Persistent Opioid Use After Surgery v1
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Ryan Howard, Craig Brown, Vidhya Gunaseelan, Michael Englesbe, Jennifer Waljee, Mark Bicket, Andrew Ryan, and Chad Brummett
- Abstract
The Opioid Prescribing Engagement Network (OPEN) at the University of Michigan was established in 2016 with the goal of reducing excessive opioid prescribing after surgery using evidence-based prescribing guidelines. Beginning in July 2016, OPEN began a statewide quality improvement campaign to educate providers and share prescribing best practices. In October 2017, the first prescribing guidelines were released. Although these efforts have been associated with significant decreases in postoperative opioid prescribing, it is unknown whether the incidence of new persistent opioid use after surgery has changed as well. This retrospective study examines the effect of these efforts on new persistent opioid use after surgery compared to the rest of the United States - including other states where no such program existed - using a difference-in-differences approach.
- Published
- 2021
34. Malignant transformation of an ileostomy stoma scar: an unusual presentation
- Author
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David E. Gyorki, David Lu, Richard Zinn, Andrew Ryan, and Catherine Mitchell
- Subjects
medicine.medical_specialty ,Ileostomy ,business.industry ,General surgery ,MEDLINE ,Surgical Stomas ,Ileostomy - stoma ,General Medicine ,Malignant transformation ,Cicatrix ,Postoperative Complications ,Colostomy ,medicine ,Humans ,Surgery ,Presentation (obstetrics) ,business - Published
- 2020
35. Follicular mucinosis with novel dermoscopic finding: the toothpaste sign
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Blake Phillip Mumford, Andrew Ryan, Alvin H. Chong, and Anita Lasocki
- Subjects
Dermatology - Published
- 2022
36. Assessment of ocean analysis and forecast from an atmosphere–ocean coupled data assimilation operational system
- Author
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Catherine Guiavarc'h, Jonah Roberts-Jones, Isabella Ascione, Andrew Ryan, D. J. Lea, and Chris Harris
- Subjects
lcsh:GE1-350 ,010504 meteorology & atmospheric sciences ,Meteorology ,010505 oceanography ,Surface ocean ,Ocean forecasting ,Ocean current ,Weather forecasting ,lcsh:Geography. Anthropology. Recreation ,Numerical weather prediction ,computer.software_genre ,01 natural sciences ,Operational system ,Atmosphere ,Data assimilation ,lcsh:G ,Environmental science ,computer ,lcsh:Environmental sciences ,0105 earth and related environmental sciences - Abstract
The development of coupled atmosphere-ocean prediction systems with utility on the short-range Numerical Weather Prediction (NWP) and ocean forecasting timescales has accelerated over the last decade. This builds on a body of evidence showing the benefit, particularly for weather forecasting, of more correctly representing the feedbacks between surface ocean and atmosphere. It prepares the way for more unified prediction systems with the capability of providing consistent surface meteorology, wave and surface ocean products to users for whom this is important. Here we describe a coupled ocean-atmosphere system, with weakly coupled data assimilation, which was operationalised at the Met Office as part of the Copernicus Marine Environment Service (CMEMS). We compare the ocean performance to that of an equivalent ocean-only system run at the Met Office, and other CMEMS products. Sea surface temperatures in particular are shown to verify better than in the ocean-only systems, although other aspects including temperature profiles and surface currents are slightly degraded. We then discuss the plans to improve the current system in future as part of the development of a coupled NWP system at the Met Office.
- Published
- 2019
37. Constraining the thermal properties of planetary surfaces using machine learning: Application to airless bodies
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Roberto Furfaro, Saverio Cambioni, Andrew Ryan, Erik Asphaug, and Marco Delbo
- Subjects
010504 meteorology & atmospheric sciences ,Infrared ,FOS: Physical sciences ,Surface finish ,Machine learning ,computer.software_genre ,01 natural sciences ,Flux (metallurgy) ,Chondrite ,0103 physical sciences ,Thermal ,Surface roughness ,010303 astronomy & astrophysics ,0105 earth and related environmental sciences ,Earth and Planetary Astrophysics (astro-ph.EP) ,business.industry ,Astronomy and Astrophysics ,Regolith ,Space and Planetary Science ,Asteroid ,Physics::Space Physics ,Astrophysics::Earth and Planetary Astrophysics ,Artificial intelligence ,business ,computer ,Geology ,Astrophysics - Earth and Planetary Astrophysics - Abstract
We present a new method for the determination of the surface properties of airless bodies from measurements of the emitted infrared flux. Our approach uses machine learning techniques to train, validate, and test a neural network representation of the thermophysical behavior of the atmosphereless body given shape model, illumination and observational geometry of the remote sensors. The networks are trained on a dataset of thermal simulations of the emitted infrared flux for different values of surface rock abundance, roughness, and values of the thermal inertia of the regolith and of the rock components. These surrogate models are then employed to retrieve the surface thermal properties by Markov Chain Monte Carlo Bayesian inversion of observed infrared fluxes. We apply the method to the inversion of simulated infrared fluxes of asteroid (101195) Bennu -- according to a geometry of observations similar to those planned for NASA's OSIRIS-REx mission -- and infrared observations of asteroid (25143) Itokawa. In both cases, the surface properties of the asteroid -- such as surface roughness, thermal inertia of the regolith and rock component, and relative rock abundance -- are retrieved; the contribution from the regolith and rock components are well separated. For the case of Itokawa, we retrieve a rock abundance of about 85% for pebbles larger than the diurnal skin depth, which is about 2 cm. The thermal inertia of the rock is found to be lower than the expected value for LL chondrites, indicating that the rocks on Itokawa could be fractured. The average thermal inertia of the surface is around 750 $J s^{-1/2} K^{-1} m^{-2}$ and the measurement of thermal inertia of the regolith corresponds to an average regolith particle diameter of about 10 mm, consistently with in situ measurements as well as results from previous studies., Comment: 20 pages, 8 figures, 6 tables. Accepted for publication in Icarus
- Published
- 2019
38. Perilipin 5 Deletion in Hepatocytes Remodels Lipid Metabolism and Causes Hepatic Insulin Resistance in Mice
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Matthew J. Watt, Jennifer Chi Yi Lo, Ruth C. R. Meex, Magdalene K. Montgomery, Stacey N Keenan, Andrew Ryan, Shuai Nie, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, and Humane Biologie
- Subjects
EXPRESSION ,Male ,0301 basic medicine ,HOMEOSTASIS ,Ceramide ,medicine.medical_specialty ,HIGH-FAT DIET ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Immunoblotting ,PROTEIN ,EXERCISE ,030209 endocrinology & metabolism ,Perilipin-5 ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,Lipid droplet ,Nonalcoholic fatty liver disease ,Internal Medicine ,medicine ,Animals ,Beta oxidation ,Cells, Cultured ,Mice, Knockout ,Insulin ,ADIPOSE TRIACYLGLYCEROL LIPASE ,Lipid metabolism ,Lipid Metabolism ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,Endocrinology ,Liver ,chemistry ,ACID ,Body Composition ,Hepatocytes ,Perilipin ,SKELETAL-MUSCLE ,JNK ,SENSITIVITY ,Insulin Resistance ,Oxidation-Reduction - Abstract
Defects in hepatic lipid metabolism cause nonalcoholic fatty liver disease and insulin resistance, and these pathologies are closely linked. Regulation of lipid droplet metabolism is central to the control of intracellular fatty acid fluxes, and perilipin 5 (PLIN5) is important in this process. We examined the role of PLIN5 on hepatic lipid metabolism and systemic glycemic control using liver-specific Pliny-deficient mice (Plin5(LKO)). Hepatocytes isolated from Plin5(LKO) mice exhibited marked changes in lipid metabolism characterized by decreased fatty acid uptake and storage, decreased fatty acid oxidation that was associated with reduced contact between lipid droplets and mitochondria, and reduced triglyceride secretion. With consumption of a high-fat diet, Plin5(LKO)) mice accumulated intrahepatic triglyceride, without significant changes in inflammation, ceramide or diglyceride contents, endoplasmic reticulum stress, or autophagy. Instead, livers of Plin5(LKO)) mice exhibited activation of c-Jun N-terminal kinase, impaired insulin signal transduction, and insulin resistance, which impaired systemic insulin action and glycemic control. Re-expression of Plin5 in the livers of Plin5(LKO)) mice reversed these effects. Together, we show that Plin5 is an important modulator of intrahepatic lipid metabolism and suggest that the increased Plin5 expression that occurs with overnutrition may play an important role in preventing hepatic insulin resistance.
- Published
- 2019
39. Association of Insurance Coverage With Adoption of Sleeve Gastrectomy vs Gastric Bypass for Patients Undergoing Bariatric Surgery
- Author
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Ryan, Howard, Edward C, Norton, Jie, Yang, Jyothi, Thumma, David E, Arterburn, Andrew, Ryan, Dana, Telem, and Justin B, Dimick
- Subjects
Adult ,Male ,Gastric Bypass ,Bariatric Surgery ,General Medicine ,Middle Aged ,Medicare ,Insurance Coverage ,United States ,Obesity, Morbid ,Cross-Sectional Studies ,Gastrectomy ,Weight Loss ,Humans ,Female ,Aged - Abstract
Instrumental variables can control for selection bias in observational research. However, valid instruments are challenging to identify.To evaluate regional variation in sleeve gastrectomy following insurance coverage implementation as an instrumental variable in comparative effectiveness research.This serial cross-sectional study included adult patients in a national Medicare claims database who underwent sleeve gastrectomy or Roux-en-Y gastric bypass from 2012 to 2017. Data analysis was performed from January to June 2021.Laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass.The association of the instrumental variable with treatment (ie, undergoing sleeve gastrectomy), as well as mortality, complications, emergency department visits, hospitalization, reinterventions, and surgical revision.A total of 76 077 patients underwent bariatric surgery, of whom 44 367 underwent sleeve gastrectomy (mean [SD] age, 56.9 [11.9] years; 32 559 [73.5%] women) and 31 710 underwent gastric bypass (mean (SD) age, 55.9 (11.8) years; 23 750 [74.9%] women). After insurance coverage initiation, there was substantial regional and temporal variation in adoption of sleeve gastrectomy. Prior-year state-level utilization of sleeve gastrectomy was highly associated with undergoing sleeve gastrectomy (Kleibergen-Paap Wald F statistic, 910.3). All but 2 patient characteristics (race and diagnosis of depression) were well-balanced between the top and bottom quartiles of the instrumental variable. Regarding 1-year outcomes, compared with patients undergoing gastric bypass, patients undergoing sleeve gastrectomy had a lower 1-year risk of mortality (0.9%; 95% CI, 0.8%-1.1% vs 1.7%; 95% CI, 1.3%-2.0%), complications (11.6%; 95% CI, 10.9%-12.3% vs 14.1%; 95% CI, 13.0%-15.3%), emergency department visits (48.3%; 95% CI, 46.9%-49.8% vs 53.6%; 95% CI, 52.3%-55.0%), hospitalization (23.4%; 95% CI, 22.4%-24.4% vs 26.5%; 95% CI, 25.1%-28.0%), and reinterventions (8.7%; 95% CI, 8.0%-9.4% vs 12.2%; 95% CI, 11.2%-13.3%). The risk of revision was not different between groups (0.6%; 95% CI, 0.3%-0.8% vs 0.4%; 95% CI, 0.3%-0.6%).In this cross-sectional study of patients undergoing bariatric surgery, there was significant geographic variation in the use of sleeve gastrectomy following initiation of insurance coverage, which served as a strong instrument to compare 2 bariatric surgical procedures. This approach could be applied to other areas of health services research to serve as a complement to clinical trials.
- Published
- 2022
40. Cystic papillary adenoma of the seminal vesicle
- Author
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Damien M Bolton, Jonathan I. Epstein, Andrew Ryan, D. Katz, S. Appu, and Bridget Heijkoop
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Adenoma ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Histology ,Urology ,030232 urology & nephrology ,Iliac fossa ,Case Report ,Cystic papillary adenoma ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Seminal vesicle ,Prostate ,medicine ,Humans ,Azoospermia ,business.industry ,Papillary Adenoma ,Seminal Vesicles ,General Medicine ,medicine.disease ,Diseases of the genitourinary system. Urology ,medicine.anatomical_structure ,Reproductive Medicine ,030220 oncology & carcinogenesis ,Genital Neoplasms, Male ,Cystadenoma ,Adenocarcinoma ,RC870-923 ,business - Abstract
Background Primary Seminal Vesicle (SV) tumours are a rare entity, with most SV masses representing invasion of the SV by malignancy originating in an adjacent organ, most often the prostate. Previously reported primary SV epithelial tumours have included adenocarcinoma and cystadenoma, with limited prior reports of inracystic papillary structures. Case presentation A 35-year-old male presented with azoospermia, intermittent macroscopic haematuria, and mild right iliac fossa and groin pain. A papillary appearing seminal vesicle mass was found on imaging and seminal vesicoscopy. The mass was robotically excised with diagnosis of benign cystic papillary adenoma made. Conclusion In this manuscript we describe a rare case of a benign cystic papillary adenoma of the seminal vesicle, a unique histological entity differentiated from cystadenoma of the Seminal Vesicle by its papillary component.
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- 2021
41. Volume-outcome relationships for Roux-en-Y gastric bypass patients in the sleeve gastrectomy era
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Grace F, Chao, Jie, Yang, Jyothi, Thumma, Karan R, Chhabra, David E, Arterburn, Andrew, Ryan, Dana A, Telem, and Justin B, Dimick
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Treatment Outcome ,Gastrectomy ,Gastric Bypass ,Bariatric Surgery ,Humans ,Obesity, Morbid ,Retrospective Studies - Abstract
Sleeve gastrectomy is now the most common bariatric operation performed. With lower volumes of Roux-en-Y gastric bypass (RYGB), it is unclear whether decreasing surgeon experience has led to worsening outcomes for this procedure.We used State Inpatient Databases from Florida, Iowa, New York, and Washington. Bariatric surgeons were designated as those who performed ten or more bariatric procedures yearly. Patients who had RYGB were included in our analysis. Using multi-level logistic regression, we examined whether surgeon average yearly RYGB volume was associated with RYGB patient 30-day complications, reoperations, and readmissions and 1-year revisions and readmissions.From 2013 to 2017 there were 27,714 patients who underwent laparoscopic RYGB by 311 surgeons. Median surgeon volume was 77 RYGBs per year. The distribution was 10 bypasses yearly at the 5th percentile, 16 bypasses at the 10th percentile, 38 bypasses at the 25th percentile, and 133 bypasses at the 75th percentile. Multi-level regression revealed that patients of surgeons with lower RYGB volumes had small but statistically significant increased risks of 30-day complications and 1-year readmissions. At 30 days, risk for any complication was 6.71%, 6.43%, and 5.55% at 10, 38, and 133 bypasses per year, respectively (p = 0.01). Risk for readmission at 1 year was 13.90%, 13.67%, and 12.90% at 10, 38, and 133 bypasses per year, respectively (p = 0.099). Of note, volume associations with complications and reoperations due to hemorrhage and leak were not statistically significant. There was also no significant association with revisions.This is the first study to examine the association of surgeon RYGB volume with patient outcomes as the national experience with RYGB diminishes. Overall, surgeon RYGB volume does not appear to have a large effect on patient outcomes. Thus, patients can safely pursue RYGB in this early phase of the sleeve gastrectomy era.
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- 2021
42. Deep proteomic profiling unveils arylsulfatase A as a non-alcoholic steatohepatitis inducible hepatokine and regulator of glycemic control
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Magdalene K, Montgomery, Jacqueline, Bayliss, Shuai, Nie, William, De Nardo, Stacey N, Keenan, Paula M, Miotto, Hamzeh, Karimkhanloo, Cheng, Huang, Ralf B, Schittenhelm, Anthony S, Don, Andrew, Ryan, Nicholas A, Williamson, Geraldine J, Ooi, Wendy A, Brown, Paul R, Burton, Benjamin L, Parker, and Matthew J, Watt
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Proteomics ,Mice ,Diabetes Mellitus, Type 2 ,Liver ,Non-alcoholic Fatty Liver Disease ,Animals ,Glycemic Control ,Insulin Resistance ,Cerebroside-Sulfatase - Abstract
Non-alcoholic steatohepatitis (NASH) and type 2 diabetes are closely linked, yet the pathophysiological mechanisms underpinning this bidirectional relationship remain unresolved. Using proteomic approaches, we interrogate hepatocyte protein secretion in two models of murine NASH to understand how liver-derived factors modulate lipid metabolism and insulin sensitivity in peripheral tissues. We reveal striking hepatokine remodelling that is associated with insulin resistance and maladaptive lipid metabolism, and identify arylsulfatase A (ARSA) as a hepatokine that is upregulated in NASH and type 2 diabetes. Mechanistically, hepatic ARSA reduces sulfatide content and increases lysophosphatidylcholine (LPC) accumulation within lipid rafts and suppresses LPC secretion from the liver, thereby lowering circulating LPC and lysophosphatidic acid (LPA) levels. Reduced LPA is linked to improvements in skeletal muscle insulin sensitivity and systemic glycemic control. Hepatic silencing of Arsa or inactivation of ARSA's enzymatic activity reverses these effects. Together, this study provides a unique resource describing global changes in hepatokine secretion in NASH, and identifies ARSA as a regulator of liver to muscle communication and as a potential therapeutic target for type 2 diabetes.
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- 2021
43. Prostate cancer cell‐intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone
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Alex Spurling, John M. Mariadason, Lisa M. Butler, Linden J. Gearing, Niall M. Corcoran, Stefano Mangiola, Katie L. Owen, Peter I. Croucher, Natasha K Brockwell, Daniel L. Roden, Alexander Swarbrick, Ruth J. Lyons, Weng Hua Khoo, Matthew K.H. Hong, Anupama Pasam, Chia Ling Chan, Andrew Ryan, Michelle M. McDonald, Vanessa M. Hayes, Hendrika M. Duivenvoorden, Tri Giang Phan, Damien Zanker, Paul J. Hertzog, Shahneen Sandhu, Christopher M. Hovens, Marek Cmero, and Belinda S. Parker
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Male ,dormancy ,Immunology ,Bone Neoplasms ,Biochemistry ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Immune system ,Interferon ,Bone cell ,Genetics ,medicine ,Humans ,Molecular Biology ,bone metastasis ,immune evasion ,Cancer ,030304 developmental biology ,Uncategorized ,0303 health sciences ,business.industry ,Immunogenicity ,Prostatic Neoplasms ,Bone metastasis ,Articles ,prostate cancer ,medicine.disease ,Cancer cell ,Cancer research ,type I interferon ,Interferons ,Signal transduction ,business ,030217 neurology & neurosurgery ,Signal Transduction ,medicine.drug - Abstract
The latency associated with bone metastasis emergence in castrate‐resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single‐cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor‐intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor‐intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor‐intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long‐term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor‐intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone‐metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune‐based therapies in solid cancers., Tumor‐intrinsic type I IFN is lost upon outgrowth of dormant prostate cancer cells in bone, driving metastasis. Therapeutic reversal of tumor‐intrinsic IFN loss enhances tumor cell visibility and the effectiveness of systemic immunomodulatory agents against bone‐metastasis.
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- 2021
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44. The Effect of Learning Strategies and Linguistic Intelligence on the Results of English Texts Reading Comprehension for High School Students in Medan
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Tiarmayanti Novita Sonia, Andrew Ryan Hasudungan Siallagan, Sugiharto, and Abdul Muin Sibuea
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Reading comprehension ,Reading (process) ,media_common.quotation_subject ,Psychology ,Linguistic intelligence ,Linguistics ,media_common - Published
- 2021
45. A Cost–Benefit Analysis of the COVID-19 Lockdown in Ireland
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Andrew Ryan
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Government ,education.field_of_study ,Coronavirus disease 2019 (COVID-19) ,Cost–benefit analysis ,media_common.quotation_subject ,Population ,Economic decline ,language.human_language ,Irish ,Unemployment ,language ,Economics ,medicine ,Demographic economics ,Social isolation ,medicine.symptom ,education ,media_common - Abstract
Since March 12th 2020, the Irish people have endured over 400 days of lockdown restrictions. To this day, the government has failed to present the benefits versus the costs of implementing such a draconian regime on the population of Ireland. This paper illustrates that the Quality-Adjusted Life Year (QALY) and Well-Being Year (WELLBY) metrics can be used to calculate the years of statistical lives saved as a result of the lockdown, and the statistical lives lost due to a reduction in wellbeing as a result of economic decline, increased unemployment, and social isolation. The probable scenario presented in this paper suggests that the costs of lockdown are 25 times greater than the benefits, including the cost of an additional 4,536 statistical lives.
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- 2021
46. Investigation of PT symmetry breaking and exceptional points in delay-coupled semiconductor lasers
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Wilkey, Andrew Ryan
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FOS: Physical sciences ,20502 Lasers and Quantum Electronics ,Quantum Mechanics - Abstract
This research investigates characteristics of PT (parity-time) symmetry breaking in a system of two optically-coupled, time-delayed semiconductor lasers. A theoretical rate equation model for the lasers’ electric fields is presented and then reduced to a 2x2 Hamiltonian model, which, in the absence of time-delay, is PT-symmetric. The important parameters we control are the temporal separation of the lasers (τ), the frequency detuning (∆ω), and the coupling strength (κ). The detuning is experimentally controlled by varying the lasers’ temperatures, and intensity vs. ∆ωbehavior are examined, specifically how the PT-transition and the period and amplitude of sideband intensity oscillations change withκandτ. Experiments are compared to analytic predictions and numerical results, and all are found to be in good agreement. Eigenvalues, eigenvectors, and exceptional points of the reduced Hamiltonian model are numerically and analytically investigated, specifically how nonzero delay affects existing exceptional points.
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- 2021
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47. The role virtual exchange could play in helping prepare students for real-life study abroad
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Andrew Ryan
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050101 languages & linguistics ,Medical education ,05 social sciences ,050301 education ,0501 psychology and cognitive sciences ,Sociology ,Life study ,0503 education - Abstract
More and more Japanese students are studying abroad and the Japanese government has set a target of 180,000 students to study abroad each year by 2020 and is providing financial assistance to students to help achieve this goal. However, is financial assistance enough? Surveys conducted with students from a national education-focused university in northern Japan, before and after their study abroad experience, show that they feel underprepared before they leave to go overseas and regret not fulfilling the opportunities they had while abroad. The key areas identified where they needed assistance were with their English language ability, confidence building, and intercultural awareness. This paper suggests that doing a Virtual Exchange (VE) before they travel could help students in all of these areas. It could provide much needed language support, motivation to explore other cultures and share their own, and deliver the confidence to enable them to become more outgoing and make the most of the opportunities presented by studying overseas. Additionally, there is a case to be argued, that VE could help reduce the impact of culture shock. Overall, it is very likely that the use of VE prior to departure could improve students’ study abroad experience. The author also understands that more research is needed on this and proposes a further study comparing students who have studied abroad without conducting VE in advance to those who have, to try and assess its impact on the study abroad experience.
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- 2020
48. Widespread carbon-bearing materials on near-Earth asteroid (101955) Bennu
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Hannah Kaplan, Lucy F. Lim, Scott A. Sandford, Carina Bennett, Humberto Campins, M. Antonietta Barucci, Dante S. Lauretta, Victoria E. Hamilton, Daniella DellaGiustina, Benjamin Rozitis, Dennis C. Reuter, Joshua P. Emery, Andrew Ryan, Dathon Golish, and Amy Simon
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chemistry.chemical_compound ,Mineral hydration ,Multidisciplinary ,Near-Earth object ,chemistry ,Asteroid ,Spectral slope ,Carbonate ,Absorption (electromagnetic radiation) ,Space weathering ,Spectral line ,Geology ,Astrobiology - Abstract
The complex history of Bennu's surface The near-Earth asteroid (101955) Bennu is a carbon-rich body with a rubble pile structure, formed from debris ejected by an impact on a larger parent asteroid. The Origins, Spectral Interpretation, Resource Identification, Security, Regolith Explorer (OSIRIS-REx) spacecraft is designed to collect a sample of Bennu's surface and return it to Earth. After arriving at Bennu, OSIRIS-REx performed a detailed survey of the asteroid and reconnaissance of potential sites for sample collection. Three papers present results from those mission phases. DellaGiustina et al. mapped the optical color and albedo of Bennu's surface and established how they relate to boulders and impact craters, finding complex evolution caused by space weathering processes. Simon et al. analyzed near-infrared spectra, finding evidence for organic and carbonate materials that are widely distributed across the surface but are most concentrated on individual boulders. Kaplan et al. examined more detailed data collected on the primary sample site, called Nightingale. They identified bright veins with a distinct infrared spectrum in some boulders, which they interpreted as being carbonates formed by aqueous alteration on the parent asteroid. Together, these results constrain Bennu's evolution and provide context for the sample collected in October 2020. Science , this issue p. eabc3660 , p. eabc3522 , p. eabc3557
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- 2020
49. Author Correction: Shape of (101955) Bennu indicative of a rubble pile with internal stiffness
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M. Lefevre, Aaron S. Burton, Carina Bennett, J. A. Mapel, Renu Malhotra, Peter Fleming, J. McAdams, N. Mogk, R. L. Ballouz, P. H. Smith, V. Nifo, C. K. Maleszewski, Timothy D. Swindle, E. Dotto, Stephen R. Schwartz, C. May, J. Bayron, D. Patterson, D. Guevel, Ellen S. Howell, Humberto Campins, J. Kissell, E. Brown, J. Wood, E. Muhle, John Robert Brucato, J. Small, B. Miller, Oleksiy Golubov, R. Pennington, K. Harshman, J. Nelson, Catherine Elder, M. McGee, R. Burns, J. Contreras, S. Hull, D. Kubitschek, D. Noss, Andrew J. Liounis, J. Backer, B. May, G. Fitzgibbon, J. Donaldson, D. Worden, Bashar Rizk, R. Witherspoon, Catherine L. Johnson, Erica Jawin, G. Shaw, A. Aqueche, Dolores H. Hill, D. Folta, S. Ferrone, M. Lujan, Giovanni Poggiali, B. G. Williams, S. Selznick, Melissa A. Morris, K. Rios, Sara S. Russell, D. Lambert, J. Hong, Jeffrey B. Plescia, H. Bloomenthal, D. Drinnon, Olivier S. Barnouin, Derek S. Nelson, Amanda E. Toland, Michael C. Moreau, J. A. Seabrook, K. Dill, A. Mirfakhrai, K. Hyde, J. D. P. Deshapriya, Hannah Kaplan, Timothy P. McElrath, Juliette I. Brodbeck, N. Ramos, S. Stewart, James B. Garvin, Sei-ichiro Watanabe, M. Arvizu-Jakubicki, Jason P. Dworkin, Matthew A. Siegler, Collin Lewin, Masatoshi Hirabayashi, L. Bloomquist, S. Gardner, Keiko Nakamura-Messenger, A. H. Nair, M. Schmitzer, P. Haas, Julie Bellerose, Dolan E. Highsmith, L. Koelbel, C. C. Lorentson, J. Zareski, E. Queen, S. R. Chesley, Philip A. Bland, A. Cheuvront, V. E. Hamilton, Ronald G. Mink, N. Mastrodemos, H. C. Connolly, K. Bellamy, M. Killgore, A. Gardner, Y. Takahashi, M. Lambert, R. C. Espiritu, Z. Zeszut, E. T. Morton, Kevin J. Walsh, Timothy D. Glotch, M. Skeen, Brian Kennedy, Matthew R.M. Izawa, G. Neumann, F. Teti, D. Doerres, A. Hasten, F. Ciceri, D. Howell, A. Deguzman, J. Nagy, D. Vaughan, H. Ma, C. Lantz, D. N. Brack, David K. Hammond, Erwan Mazarico, Leilah K. McCarthy, L. Rhoads, Kathleen L. Craft, C. Welch, Jay W. McMahon, C. L. Parish, D. C. Reuter, M. Giuntini, N. Castro, Clive Dickinson, J. Kreiner, K. Kingsbury, S. Dickenshied, Joseph A. Nuth, Alan R. Hildebrand, Erik Asphaug, H. Ido, Eric M. Sahr, A. Harbison, Arlin E. Bartels, T. Forrester, D. Eckart, R. Bandrowski, Michael K. Barker, Robert Gaskell, J. Wendel, S. Freund, Marc Bernacki, Ryan S. Park, A. Taylor, E. B. Bierhaus, S. Millington-Veloza, J. Stromberg, L. B. Breitenfeld, K. Stakkestad, D. Ellis, Timothy J. McCoy, M. Susak, Richard G. Cosentino, C. Manzoni, Hisayoshi Yurimoto, C. Drouet d'Aubigny, A. Bjurstrom, Masako Yoshikawa, S. Francis, J. Peachey, J. Geeraert, K. Marchese, O. Billett, M. Rascon, F. Jaen, B. Diallo, Martin Miner, Kris J. Becker, E. Mazzotta Epifani, Florian Thuillet, A. Knight, James H. Roberts, Pasquale Tricarico, Edward A. Cloutis, T. Fisher, Dale Stanbridge, A. Colpo, Osiris-Rex Team, S. Gonzales, Q. Tran, M. K. Crombie, John Marshall, N. Bojorquez-Murphy, David Vokrouhlický, Allen W. Lunsford, H. Bowles, K. L. Edmundson, R. A. Masterson, Peter G. Antreasian, N. Gorius, Benjamin Rozitis, D. Pino Muñoz, S. Carlson-Kelly, C. Thayer, J. Elsila Cook, B. C. Clark, N. Piacentine, José C. Aponte, M. Al Asad, M. A. Barucci, D. Blum, P. Falkenstern, Neil Bowles, Matthew Chojnacki, J. M. Leonard, J. Daly, K. Yetter, M. R. Fisher, Jeffrey N. Grossman, A. Boggs, N. Jayakody, Cristina A. Thomas, C.M. Ernst, Namrah Habib, J. N. Kidd, R. J. Steele, Andrew B. Calloway, Andrew Ryan, Kimberly T. Tait, Paul O. Hayne, J. Y. Li, K. L. Berry, William V. Boynton, Yanga R. Fernandez, D. A. Lorenz, M. Wasser, Daniel J. Scheeres, K. Fortney, A. Scroggins, B. Allen, B. Sutter, T. Ferro, Jonathan Joseph, Derek C. Richardson, D. Hoak, Brian Carcich, W. Chang, P. Wren, C. Boyles, Kaj E. Williams, B. Marty, J. Liang, J. Hoffman, A. Harch, Daniel R. Wibben, Jamie Molaro, S. Rieger, R. Enos, C. W. Hergenrother, Stephen R. Sutton, J. Grindlay, E. J. Lessac-Chenen, E. Huettner, C. Norman, P. Sherman, L. Swanson, M. Coltrin, S. Van wal, B. Buck, A. Fisher, Kevin Righter, Brian Rush, David D. Rowlands, Lauren McGraw, A. Levine, K. Drozd, D. Gaudreau, A. Nguyen, S. Sides, M. Chodas, R. Dubisher, B. Ashman, Michael Caplinger, Amy Simon, W. Moore, S. S. Balram-Knutson, R. Carpenter, S. Fornasier, Shogo Tachibana, Russell Turner, Ian A. Franchi, Trevor Ireland, Chloe B. Beddingfield, D. F. Everett, M. Corvin, Lindsay P. Keller, Tammy L. Becker, S. Carter, J. L. Rizos Garcia, Mark E. Perry, E. Keates, Michael C. Nolan, P. Vasudeva, C. Fellows, K. Herzog, Mark A. Jenkins, J. R. Weirich, J. Swenson, D. R. Golish, Davide Farnocchia, Lydia C. Philpott, Rebecca R. Ghent, Hannah C.M. Susorney, S. W. Squyres, Pedro Hasselmann, J. Hill, Thomas J. Zega, B. Key, Marco Delbo, A. S. French, P. Sánchez, A. Hilbert, J. Y. Pelgrift, R. P. Binzel, L. McNamara, Vishnu Reddy, Michael Daly, Scott Messenger, Daniella DellaGiustina, Maurizio Pajola, Charles Brunet, Joshua L. Bandfield, J. Padilla, A. Janakus, M. Moreau, R. Garcia, R. A. Chicoine, P. Michel, P. Kaotira, K. S. Johnson, J. Forelli, G. Miller, K. Martin, I. Galinsky, S. Desjardins, Naru Hirata, Christine Hartzell, M. L. Jones, S. Hooven, D. Velez, R. Munoz, Carolyn M. Ernst, C. Emr, N. Martinez-Vlasoff, S. Bendall, R. Zellar, E. Church, Theodore Kareta, T. Warren, P. Wolff, V. Morrison, C. Bryan, S. Bhaskaran, N. Jones, D. Hauf, Jeremy Bauman, R. T. Daly, R. Olds, M. M. Westermann, D. K. Hamara, E. Audi, G. Johnston, Eric Palmer, Courtney Mario, Daniel P. Glavin, T. Haltigin, J. Cutts, Javier Licandro, Xiao-Duan Zou, H. L. Roper, Gregory A. Neumann, William M. Owen, S. Sugita, Y. H. Tang, Kevin Burke, H. L. Enos, D. Gallagher, William F. Bottke, K. Getzandanner, Philip R. Christensen, C. W. V. Wolner, K. Fleshman, D. Poland, J. P. Emery, M.M. Riehl, D. Fennell, D. Sallitt, A. D. Rogers, M. Fitzgibbon, John H. Jones, S. Mullen, S. Salazar, S. Oliver, A. T. Polit, J. Cerna, A. Praet, Mark E. Holdridge, E. M. Ibrahim, Coralie D. Adam, J. de León, Christopher J. Miller, M. Ryle, J. Lyzhoft, M. Loveridge, C. Hoekenga, Brent J. Bos, S. Anwar, K. Chaffin, Devin L. Schrader, B. Lovelace, Romy D. Hanna, C. D. Adam, G. L. Mehall, K. L. Donaldson Hanna, F. Merlin, B. Wright, Guy Libourel, L. F. Lim, N. Shultz, Dante S. Lauretta, K. Hanley, Beth E. Clark, L. Le Corre, K. Thomas-Keprta, Moses Milazzo, W. Hagee, B. Page, M. Fisher, E. McDonough, D. Trang, S. Clemett, A. Rubi, A. Ingegneri, Scott A. Sandford, D. Dean, J. Freemantle, Michael D. Smith, Christopher W. Haberle, L. Nguyen, M. Fulchignoni, Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL), Centre de Mise en Forme des Matériaux (CEMEF), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)
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[PHYS]Physics [physics] ,010504 meteorology & atmospheric sciences ,Rubble ,Stiffness ,engineering.material ,010502 geochemistry & geophysics ,01 natural sciences ,[SDU]Sciences of the Universe [physics] ,engineering ,medicine ,General Earth and Planetary Sciences ,Geotechnical engineering ,medicine.symptom ,Pile ,[PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph] ,Geology ,ComputingMilieux_MISCELLANEOUS ,0105 earth and related environmental sciences - Abstract
International audience
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- 2020
50. Thermophysical Analysis of Regolith on (101955) Bennu: The Coarse Regolith Conundrum
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Philip R. Christensen, Carina Bennett, Marco Delbo, Joshua P. Emery, Marc Bernacki, Andrew Ryan, Dante S. Lauretta, K. N. Burke, Victoria E. Hamilton, Daniel Pino Muñoz, Matthew A. Siegler, Ben Rozitis, and Saverio Cambioni
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Regolith ,Geology ,Astrobiology - Abstract
Thermophysical analyses of planetary bodies such as the Moon, Mars, and numerous asteroids have allowed for remote estimates of regolith physical properties, such as particle size and packing density, as well as the relative spatial abundance of boulders. Here we define “regolith” as a particulate assemblage where most particles are comparable to or smaller than the length scale of the diurnal skin depth (the e-folding depth of the diurnal thermal wave). Until recently, regolith and boulders were believed to be thermally quite distinct; regolith on the Moon, Mars, and most asteroids was usually known or suspected to be fine (i.e., ranging from fine dust to sand), meaning that it was known or assumed to have a thermal inertia much lower than that of boulders and bedrock. Upon the arrival of NASA OSIRIS-REx at asteroid Bennu and JAXA Hayabusa2 at asteroid Ryugu and the subsequent thermophysical analyses of the respective asteroid surfaces, this preconceived notion of thermophysically distinct regolith and boulders/bedrock was found to be flawed (DellaGiustina and Emery et al., 2019; Sugita et al., 2019). Boulders cover the vast majority of both asteroids’ surfaces, yet the thermal inertia values determined for these boulder-rich surfaces fall within a range that was previously believed to exclusively represent coarse, sand-to-pebble–sized regolith. Recent work has been devoted to the analysis of the boulders’ thermal inertia and the physical interpretation thereof (Grott et al., 2019; Rozitis et al., in revision); the general conclusion so far is that the boulders have very low thermal conductivity and density owing to the presence of numerous pores and fractures, more so than most (or perhaps all) carbonaceous chondrite meteorites in Earth’s collections. As such, these boulders are likely to be structurally distinct from all known meteorite specimens. Although fine-particulate regolith is rare on the surface of Bennu, it is present in some locations. It is still of great interest to probe the physical properties of this regolith by means of thermal analysis so as to make predictions about the properties of the samples that will be returned by OSIRIS-REx and to learn about the evolution of the asteroid surface and the mechanisms by which regolith is produced and lost or destroyed. There remains the enigmatic question: although we suspect that the boulders on Bennu are distinct from the meteorite collection, will the returned samples of particulate material share these distinct properties? At what scales can we define the physical thermally relevant properties of boulders and regolith particles on Bennu? In other words, if the boulders are indeed highly fractured and porous, are the regolith particles also fractured and porous or are their dimensions below the relevant length scales? It is very challenging to estimate the physical properties of the regolith on Bennu using thermal data, even in regions where it appears to be abundant, due to the coarseness of the regolith. Commonly used planetary thermophysical models rely on the assumption that the material on the surface, be it regolith or rock, can be approximated as a continuous, non-discretized material with physical properties that are either constant with depth or are allowed to vary with depth in some well-defined way (e.g. an exponential density increase, or up to a few layers of physically distinct material, such as regolith on bedrock or dust coatings). This assumption of material continuity is valid when regolith particles are smaller, or perhaps even much smaller, than the diurnal skin depth of the thermal wave. However, high-resolution images of the Nightingale Crater on Bennu, which is the OSIRIS-REx mission’s primary sample collection site, revealed a particle size frequency distribution (SFD) that crosses this threshold; i.e., there are particles present that are smaller than, comparable to, and larger than the diurnal skin depth (~1–5 cm) present within a single, meters-wide observation footprint. The thermophysical behavior of such a regolith configuration has never been comprehensively studied and likely cannot be properly approximated with standard 1D thermal modeling methods. We will present preliminary results using a 3D regolith model where we render hundreds of regolith particles and rocks, approximated as spheres, in a finite element mesh framework. The model is heated diurnally with a solar source to study the thermal response of such skin depth–crossing SFDs under Bennu surface-like conditions. The SFD of the particles is informed by particle size counts in Nightingale Crater from high-resolution visible images. With the SFD partially constrained, we are able to focus our efforts on exploring the material property parameter space, namely to estimate the thermal conductivity and density of individual regolith particles. Given the coarseness of the regolith on Bennu, we find that the model is more sensitive than one might expect to the thermal conductivity of the individual regolith particles owing to the effects of particle non-isothermality (Ryan et al., 2020). Although this present modeling work is focused on analyzing thermal emission data of Bennu obtained by the OSIRIS-REx Thermal Emission Spectrometer (OTES, Christensen et al., 2018), we aim to expand our efforts to study the more general thermal behavior of coarse regoliths and regoliths with wide SFDs under a range of solar heating conditions. Acknowledgements This material is based upon work supported by NASA under Contract NNM10AA11C issued through the New Frontiers Program. We are grateful to the entire OSIRIS-REx Team for making the encounter with Bennu possible. References: Christensen, P.R. et al. (2018). The OSIRIS-REx Thermal Emission Spectrometer (OTES) Instrument. Space Science Reviews 214, 87. DellaGiustina, D.N., Emery, J.P., et al. (2019) Properties of rubble-pile asteroid (101955) Bennu from OSIRIS-REx imaging and thermal analysis, Nature Astronomy, DOI:10.1038/s41550-019-0731-1. Grott, M., Knollenberg, J., et al. (2019) Low thermal conductivity boulder with high porosity identified on C-type asteroid (162173) Ryugu, Nature Astronomy, DOI:10.1038/s41550-019-0832-x. Rozitis, B., Ryan, A.J., Emery, J.P., et al. (in revision) Asteroid (101955) Bennu’s Weak Boulders and Thermally Anomalous Equator, Science Advances, submitted March 2020. Ryan, A., Pino Muñoz, D., Bernacki, M., Delbo, M. (2020) Full-Field Modeling of Heat Transfer in Asteroid Regolith: Radiative Thermal Conductivity of Polydisperse Particulates, JGR:Planets. DOI:10.1029/2019JE006100. Sugita, S., Honda, R., et al. (2019) The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes, Science. DOI:10.1126/science.aaw0422
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- 2020
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