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Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

Landy, Justin F; Jia, Miaolei Liam; Ding, Isabel L; Viganola, Domenico; Tierney, Warren; Dreber, Anna; Johannesson, Magnus; Pfeiffer, Thomas; Ebersole, Charles R; Gronau, Quentin F; Ly, Alexander; van den Bergh, Don; Marsman, Maarten; Derks, Koen; Wagenmakers, Eric-Jan; Proctor, Andrew; Bartels, Daniel M; Bauman, Christopher W; Brady, William J; Cheung, Felix; Cimpian, Andrei; Dohle, Simone; Donnellan, M Brent; Hahn, Adam; Hall, Michael P; Jiménez-Leal, William; Johnson, David J; Lucas, Richard E; Monin, Benoît; Montealegre, Andres; Mullen, Elizabeth; Pang, Jun; Ray, Jennifer; Reinero, Diego A; Reynolds, Jesse; Sowden, Walter; Storage, Daniel; Su, Runkun; Tworek, Christina M; Van Bavel, Jay J; Walco, Daniel; Wills, Julian; Xu, Xiaobing; Yam, Kai Chi; Yang, Xiaoyu; Cunningham, William A; Schweinsberg, Martin; Urwitz, Molly; Uhlmann, Eric L
To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from 2 separate large samples (total N > 15,000) were then randomly assigned to complete 1 version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: Materials from different teams rendered statistically significant effects in opposite directions for 4 of 5 hypotheses, with the narrowest range in estimates being d = -0.37 to + 0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for 2 hypotheses and a lack of support for 3 hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, whereas considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
PMID: 31944796
ISSN: 1939-1455
CID: 4263812

A phase 1b/2a trial of tofacitinib, an oral janus kinase inhibitor, in systemic lupus erythematosus [Meeting Abstract]

Hasni, S; Gupta, S; Davis, M A; Poncio, E; Temesgen-Oyelakin, Y; Biehl, A; Carlucci, P; Wang, X; Ochoa-Navas, I; Manna, Z G; Naqi, M; Shi, Y; Thomas, D E; Chen, J; Biancotto, A; Apps, R; Cheung, F; Kotiliarov, Y; Babyak, A; Stagliano, K; Tsai, W; Vian, L; Gazaniga, N R; Giudice, V; Playford, M; Brooks, S; Goel, R R; MacKay, M; Gregersen, P; Diamond, B; Li, X; Remaley, A; Mehta, N; O'Shea, J; Gadina, M; Kaplan, M J
Background A pharmacologic intervention that modulates JAK/ STAT signaling pathways represents a novel approach for the treatment of Systemic Lupus Erythematosus (SLE). In animal models of SLE, tofacitinib improved clinical features, immune dysregulation and vascular dysfunction. The STAT4 risk allele is associated with higher risk of severe manifestations in SLE. We hypothesized that immune modulation in response to JAK/ STAT inhibition would be more robust in SLE subjects that carry the STAT4 risk allele. Methods We conducted a phase 1b/2a randomized, doubleblind, placebo-controlled clinical trial of oral tofacitinib, 5 mg twice daily, in 30 SLE subjects (2:1 drug to placebo ratio) with mild to moderate disease activity, stratified by the presence or absence of STAT4 risk allele. Study duration was 84 days (56 days of active treatment ; 28 days of off drug). In addition to recording adverse events (AEs), lipoprotein profile, non-invasive vascular function studies, immuno-phenotyping, and gene expression studies were performed. Results Tofacitinib was well tolerated with no worsening of SLE disease activity, and no severe AEs, opportunistic infections or liver function abnormalities. A total of 43 AEs (mostly mild respiratory infections) occurred in the treated group compared to 28 AEs in placebo. There was a significant increase in HDL-C and HDL particle size in tofacitinib-treated patients at day 56 (p=0.006) accompanied by significant improvements in plasma protein lecithin: cholesterol acyltransferase (LCAT) concentration. There were also trends for improvements in vascular stiffness in the tofacitinib-treated group. The Interferon response genes (type I IFN), the levels of low- density granulocytes (LDGs) and neutrophil extracellular trap (NET remnants) significantly decreased in the tofacitinib treated group who were STAT 4 risk allele positive but not in the placebo group at day 56, accompanied by significant changes in pSTAT phosphorylation of different immune cells. Levels of activation and checkpoint markers CD103, CXCR3, ICOS, and PD-1 were significantly decreased on multiple T cell subsets, in tofacitinib treated individuals that lack the STAT4 risk allele. Conclusions In a short-term trial, tofacitinib was well tolerated in SLE subjects with mild-moderate disease activity. Use of tofacitinib resulted in improvements in lipoprotein profile and HDL function and decreases in the type I IFN and aberrant neutrophil responses characteristic of SLE. Long-term studies are needed to determine the efficacy of tofacitinib in the various manifestations of SLE. (Figure Presented)
ISSN: 2053-8790
CID: 3861232

Dorsolateral fibromuscular tissue preservation during artificial urinary sphincter cuff placement is associated with low infection and erosion rates

Cheung, Felix; Fathollahi, Ali; Vertosick, Emily; Jarvis, Thomas R; Katz, Darren; Sandhu, Jaspreet S
OBJECTIVES/OBJECTIVE:To present a modified technique in artificial urinary sphincter (AUS) placement that is associated with low rates of erosion and infection in a high-risk population. PATIENTS AND METHODS/METHODS:After Institutional Review Board approval, we identified patients who underwent primary AUS placement using the modified technique between January 2007 and November 2015. Our modification consists of preserving the dorsolateral fibromuscular tissue surrounding the bulbar urethra and horizontally transecting the ventral bulbospongiosus muscle during urethral cuff placement. Preoperative variables such as radiotherapy (RT) and bladder neck contractures were recorded. Effectiveness and complications including infections, erosions, and re-operations were recorded at follow-up. RESULTS:The new technique was used on 208 patients: 40% had a history of RT, including 15% who had had a salvage radical prostatectomy; 26% had had previous bladder neck contractures. No patients developed infection. Overall, erosion occurred in six (2.9%) patients and spontaneous erosions occurred in two (0.9%) during the study period. In all, 21 patients underwent re-operation for device failure. The probability of re-operation for 'any' reason was 7% (95% confidence interval [CI] 4-12%) at 1 year. The 1-year social continence rate was 74% (95% CI 67-81%). CONCLUSION/CONCLUSIONS:Preservation of dorsolateral fibromuscular tissue during AUS placement is an effective means to achieve a low risk of erosions. Our modified technique is safe with low infection and erosion rates, whilst maintaining good functional outcomes despite a high-risk population.
PMID: 29972627
ISSN: 1464-410x
CID: 3498662

Voiding Dysfunction After Non-urologic Pelvic Surgery

Cheung, Felix; Sandhu, Jaspreet S
PURPOSE OF REVIEW/OBJECTIVE:Urinary dysfunction is a common entity in patients undergoing radical pelvic surgery for non-urologic malignancies. These dysfunctions may manifest as lower urinary tract symptoms (LUTS) or signs such as urinary retention or leakage. Review of current literature is performed to describe the differing urinary dysfunctions that manifest after colorectal resection, hysterectomy, and sacrectomy. RECENT FINDINGS/RESULTS:Conventional radical surgery for pelvic malignancies often will result in debilitating functional problems. As advances in surgical techniques and management options become more available, patients can have better functional outcomes, specifically in the lower urinary tract. Nerve-sparing techniques as well as vascular preservation are becoming more important to preserve function as patient survival is improving. Additionally, newer methods are being explored, such as nerve stimulation for those who are unable to empty adequately. This article also addresses different management options for specific voiding dysfunction that may result from pelvic surgery. Preventative strategies such as nerve preservation during surgery are an important concept to prevent urinary dysfunction. The goal to good functional outcomes includes maintaining reservoir compliance and capacity as well as allowing proper outlet for voiding. We discuss different modalities to help achieve a functional lower urinary tract for patients with lower urinary tract dysfunction after pelvic surgery.
PMID: 30083849
ISSN: 1534-6285
CID: 3498672

Lytic Bone Lesion in Endometrial Carcinoma A Case Report

May, J. Stuart; Cheung, Felix; Zgheib, Nadim Bou
BACKGROUND: Endometrial cancer is the most common gynecologic malignancy and the fourth most common of all malignancies in women. The usual presenting symptom is postmenopausal bleeding. Most cases are stage I or II when diagnosed. Osseous metastasis is rare (0-2% of cases) and is known to be a poor prognostic indicator.
ISSN: 0024-7758
CID: 3495292

Bacteria on Urine Microscopy Is Not Associated with Systemic Infection in Patients with Obstructing Urolithiasis

Cheung, Felix; Loeb, Charles A; Croglio, Michael P; Waltzer, Wayne C; Weissbart, Steven J
INTRODUCTION:Determining whether bacterial presence in urine microscopy represents infection is important as ureteral stent placement is indicated in patients with obstructing urolithiasis and infection. We aim to investigate whether the presence of bacteria on urine microscopy is associated with other markers of infection in patients with obstructing urolithiasis presenting to the emergency room. METHODS:We performed a cross-sectional study of 199 patients with obstructing urolithiasis and divided patients into two groups according to the presence of bacteria on urine microscopy. The primary outcome was serum white blood cell count and secondary outcomes were objective fever, subjective fever, tachycardia, pyuria, and final urine culture. Univariate and multivariate analysis were used to assess whether the presence of bacteria on microscopy was associated with other markers of infection. RESULTS:The study included 72 patients in the bacteriuria group and 127 without bacteriuria. On univariate analysis, the presence of bacteria was not associated with leukocytosis, objective fever, or subjective fever, but it was associated with gender (p < 0.001), pyuria (p < 0.001), positive nitrites (p = 0.001), positive leukocyte esterase (p < 0.001), and squamous epithelial cells (p = 0.002). In a multilinear regression model including the presence of squamous cells, age, and sex, the presence of bacteriuria was not related to serum white blood cell count (coefficient -0.47; 95% confidence interval [CI] -1.1, 0.2; p = 0.17), heart rate (coefficient 0.85; 95% CI -2.5, 4.2; p = 0.62), presence of subjective or objective fever (odds ratio [OR] 1.5; 95% CI 0.8, 3.1; p = 0.18), or the presence of squamous epithelial cells (coefficient -4.4; 95% CI -10, 1.2; p = 0.12). However, the presence of bacteriuria was related to only the degree of pyuria (coefficient 16.4; 95% CI 9.6, 23.3; p < 0.001). CONCLUSIONS:Bacteria on urine microscopy is not associated with other markers of systemic infection and may largely represent a contaminant. Renal colic may be a risk factor for providing a contaminated urine specimen.
PMID: 28558478
ISSN: 1557-900x
CID: 4269852


Kapadia, Kailash; Chen, Andrew; Redger, Kirk; Cheung, Felix; Adler, Howard L.
ISSN: 0022-5347
CID: 3495222

Methylene Blue Causing Serotonin Syndrome Following Cystocele Repair

Kapadia, Kailash; Cheung, Felix; Lee, Wai; Thalappillil, Richard; Florence, F Barry; Kim, Jason
Methylene blue is an intravenously administered agent that may potentiate serotonin syndrome. The usage of methylene blue to evaluate ureters for injuries and patency during urological surgeries is recognized as common practice. However, there is no mention of serotonin syndrome caused by methylene blue in urological literature or for urological surgery. We report the first urological case in order to raise awareness of the risk for serotonin toxicity with utilizing methylene blue.
PMID: 27617215
ISSN: 2214-4420
CID: 3498642

The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline

Schweinsberg, Martin; Madan, Nikhil; Vianello, Michelangelo; Sommer, S. Amy; Jordan, Jennifer; Tierney, Warren; Awtrey, Eli; Zhu, Luke Lei; Diermeier, Daniel; Heinze, Justin E.; Srinivasan, Malavika; Tannenbaum, David; Bivolaru, Eliza; Dana, Jason; Davis-Stober, Clintin P.; du Plessis, Christilene; Gronau, Quentin F.; Hafenbrack, Andrew C.; Liao, Eko Yi; Ly, Alexander; Marsman, Maarten; Murase, Toshio; Qureshi, Israr; Schaerer, Michael; Thornley, Nico; Tworek, Christina M.; Wagenmakers, Eric Jan; Wong, Lynn; Anderson, Tabitha; Bauman, Christopher W.; Bedwell, Wendy L.; Brescoll, Victoria; Canavan, Andrew; Chandler, Jesse J.; Cheries, Erik; Cheryan, Sapna; Cheung, Felix; Cimpian, Andrei; Clark, Mark A.; Cordon, Diana; Cushman, Fiery; Ditto, Peter H.; Donahue, Thomas; Frick, Sarah E.; Gamez-Djokic, Monica; Grady, Rebecca Hofstein; Graham, Jesse; Gu, Jun; Hahn, Adam; Hanson, Brittany E.; Hartwich, Nicole J.; Hein, Kristie; Inbar, Yoel; Jiang, Lily; Kellogg, Tehlyr; Kennedy, Deanna M.; Legate, Nicole; Luoma, Timo P.; Maibuecher, Heidi; Meindl, Peter; Miles, Jennifer; Mislin, Alexandra; Molden, Daniel C.; Motyl, Matt; Newman, George; Ngo, Hoai Huong; Packham, Harvey; Ramsay, Philip S.; Ray, Jennifer L.; Sackett, Aaron M.; Sellier, Anne Laure; Sokolova, Tatiana; Sowden, Walter; Storage, Daniel; Sun, Xiaomin; Van Bavel, Jay J.; Washburn, Anthony N.; Wei, Cong; Wetter, Erik; Wilson, Carlos T.; Darroux, Sophie Charlotte; Uhlmann, Eric Luis
This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had "in the pipeline" as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed.
ISSN: 0022-1031
CID: 3936352


Lee, Wai; D'Amato, Abram; Cheung, Felix; Tam, Justina; Sobey, Steven; Waltzer, Wayne; Corcoran, Anthony
ISSN: 0022-5347
CID: 3494142