Distilling Information Reliability and Source Trustworthiness from Digital Traces

Online knowledge repositories typically rely on their users or dedicated editors to evaluate the reliability of their content. These evaluations can be viewed as noisy measurements of both information reliability and information source trustworthiness. Can we leverage these noisy evaluations, often biased, to distill a robust, unbiased and interpretable measure of both notions? In this paper, we argue that the temporal traces left by these noisy evaluations give cues on the reliability of the information and the trustworthiness of the sources. Then, we propose a temporal point process modeling framework that links these temporal traces to robust, unbiased and interpretable notions of information reliability and source trustworthiness. Furthermore, we develop an efficient convex optimization procedure to learn the parameters of the model from historical traces. Experiments on real-world data gathered from Wikipedia and Stack Overflow show that our modeling framework accurately predicts evaluation events, provides an interpretable measure of information reliability and source trustworthiness, and yields interesting insights about real-world events.Comment: Accepted at 26th World Wide Web conference (WWW-17

Natural history and clinical effect of aortic valve regurgitation after left ventricular assist device implantation

ObjectivesAortic valve regurgitation reduces left ventricular assist device mechanical efficiency. Evidence has also suggested that left ventricular assist device implantation can induce or exacerbate aortic valve regurgitation. However, this has not been compared with aortic valve regurgitation progression in a nonsurgical end-stage heart failure population. Furthermore, its clinical effect is unclear. We sought to characterize the development and progression of aortic valve regurgitation in left ventricular assist device recipients and to identify its clinical effect.MethodsA review of all consecutive patients who received an intracorporeal left ventricular assist device at Duke University Medical Center from January 2004 to January 2011 was conducted. Cases of previous or concomitant aortic valve surgery were excluded. Data from the remaining implants (n = 184) and a control group of contemporaneous nonsurgical patients with end-stage heart failure (n = 132) were analyzed. Serial transthoracic echocardiography was used to characterize aortic valve regurgitation as a function of time.ResultsLeft ventricular assist device implantation was associated with worsening aortic valve regurgitation, defined as an increase in aortic valve regurgitation grade, relative to the nonsurgical patients with end-stage heart failure (P < .0001). The recipients of continuous flow left ventricular assist devices were more likely than recipients of pulsatile left ventricular assist devices to develop worsening aortic valve regurgitation (P = .0348). Moderate or severe aortic valve regurgitation developed in 21 left ventricular assist device recipients; this was unrelated to the type of device implanted (continuous vs pulsatile; P = .754) or aortic valve regurgitation grade before left ventricular assist device implantation (P = .42). Five patients developed severe aortic valve regurgitation; all of whom underwent aortic valve procedures.ConclusionsNative aortic valve regurgitation developed and/or progressed after left ventricular assist device implantation, with this effect being more pronounced in continuous flow left ventricular assist device recipients. However, the preoperative aortic valve regurgitation grade failed to correlate with the development of substantial aortic valve regurgitation after left ventricular assist device implantation. After left ventricular assist device implantation, aortic valve regurgitation had a small, but discernible, clinical effect, with some patients developing severe aortic valve regurgitation and requiring aortic valve procedures. These data have implications for the long-term management of left ventricular assist device recipients, in particular as the durability of implantable continuous flow left ventricular assist device therapy improves

Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model

ObjectiveAchieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model.MethodsNine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device. All animals were acutely killed, and the left atrium was fixed in formalin. Protocolized histological sections (5 μm) were obtained throughout each lesion and prepared with Masson trichrome and hematoxylin and eosin staining. Measurements were performed on a total of 359 slides from the 9 lesions. In addition, fresh left atrial tissues from 18 unused human donor hearts that did not meet the criteria for cardiac transplantation were measured at the site where the high-intensity focused ultrasound device is normally applied.ResultsCalf left atrial thickness ranged between 2.5 and 20.1 mm, with a mean of 9.10 mm. High-intensity focused ultrasound ablation consistently produced a 100% transmural lesion in left atrial thickness up to 6 mm. In addition, a transmural lesion was observed in 91% of tissues that were up to 10 mm thick and in 85% that were up to 15 mm thick. Human left atrial thickness ranged between 1.2 to 6 mm, with a mean of 3.7 mm.ConclusionsCalf left atrial thickness in this study was greater than human left atrial thickness. Human left atrial thickness is generally less than 6 mm, and in this range high-intensity focused ultrasound ablation achieved 100% transmurality. These histological results might correlate with a high success rate of atrial fibrillation ablation by using the high-intensity focused ultrasound system

Twenty-five-year outcomes after multiple internal thoracic artery bypass

ObjectiveCoronary artery bypass grafting with multiple internal thoracic artery grafts is currently controversial. This study assessed single institutional outcomes with multiple internal thoracic artery grafting for guidance with future clinical decisions.MethodsIn 19,482 patients undergoing multivessel coronary artery bypass grafting (1984-2009), baseline characteristics were recorded in a prospective databank, and follow-up was obtained by questionnaires, phone contact, or National Death Index. Outcomes examined were subsequent myocardial infarction, percutaneous coronary intervention, reoperative coronary artery bypass grafting, all-cause death, and a composite of the 4. Three groups were defined: (1) no internal thoracic artery graft (1874/19,482 or 9%); (2) single internal thoracic artery grafts and adjunctive venous conduits (single internal thoracic artery; 16,881/19,482 or 87%); and (3) multiple internal thoracic artery grafts (728/19,482 or 4%). Multivariable Cox modeling adjusted for differences in baseline characteristics, and comparisons were performed using area under the curve analysis.ResultsDifferences in baseline characteristics for the no internal thoracic artery graft, single internal thoracic artery, and multiple internal thoracic artery groups were as follows: median age 66, 64, and 59 years, respectively; congestive heart failure 22%, 18%, and 13%, respectively; ejection fraction 0.50, 0.52, and 0.51, respectively; reoperation 10%, 3%, and 7%, respectively; diabetes 27%, 30%, and 15%, respectively; and female gender 33%, 28%, and 20%, respectively. No differences existed in the median number of diseased vessels (3, 3, and 3, respectively) or number of grafts per patient (3, 3, and 3, respectively). Composite outcome improved with increasing internal thoracic artery grafts, whether assessing unadjusted or risk-adjusted data. Compared with no internal thoracic artery graft, the adjusted hazard ratio was 0.79 (confidence interval, 0.74-0.83) for single internal thoracic artery grafting and 0.70 (confidence interval, 0.62-0.80) for multiple internal thoracic artery grafting (both P < .001), reducing risk by 21% and 30%, respectively.ConclusionsThis study confirms improved patient outcomes with multiple internal thoracic artery grafting, achieving half again as much benefit as single internal thoracic artery grafting alone. The data suggest that increasing application of multiple internal thoracic artery grafting should be encouraged to mitigate the inherent risks and costs of long-term cardiac events

Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney

Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag[superscript −/−] mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag[superscript −/−] mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag[superscript −/−] liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.National Institutes of Health (U.S.) (Grant R01-CA055042)National Institutes of Health (U.S.) (Grant R01-CA149261)National Institutes of Health (U.S.) (Grant P30-ES02109)Ellison Medical Foundatio

Modified Back Projection Kernel Based Image Super Resolution

In this paper, we propose a new super resolution technique based on iterative interpolation followed by registering them using back projection (BP). Firstly the low resolution image is interpolated and then decimated to four low resolution images. The four low resolution images are interpolated and registered by using BP in order to generate a sharper high resolution image then high resolution image is down sampled and back to the first step. The proposed method has been tested on some bench mark images. The peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) results as well as the visual results shows the superiority of the proposed technique over the conventional and state-of-art image super resolution techniques. In Average, the PSNR is 2.72 dB higher than the bicubic interpolation

A New Spontaneously Transformed Syngeneic Model of High-Grade Serous Ovarian Cancer with a Tumor-Initiating Cell Population

Improving screening and treatment options for patients with epithelial ovarian cancer has been a major challenge in cancer research. Development of novel diagnostic and therapeutic approaches, particularly for the most common subtype, high-grade serous ovarian cancer (HGSC), has been hampered by controversies over the origin of the disease and a lack of spontaneous HGSC models to resolve this controversy. Over long-term culture in our laboratory, an ovarian surface epithelial (OSE) cell line spontaneously transformed OSE (STOSE). The objective of this study was to determine if the STOSE cell line is a good model of HGSC. STOSE cells grow faster than early passage parental M0505 cells with a doubling time of 13 and 48 h, respectively. STOSE cells form colonies in soft agar, an activity for which M0505 cells have negligible capacity. Microarray analysis identified 1755 down-regulated genes and 1203 up-regulated genes in STOSE compared to M0505 cells, many associated with aberrant Wnt/β-catenin and Nf-κB signaling. Upregulation of Ccnd1 and loss of Cdkn2a in STOSE tumors is consistent with changes identified in human ovarian cancers by The Cancer Genome Atlas. Intraperitoneal injection of STOSE cells into severe combined immunodeficient and syngeneic FVB/N mice produced cytokeratin+, WT1+, inhibin−, and PAX8+ tumors, a histotype resembling human HGSC. Based on evidence that a SCA1+ stem cell-like population exists in M0505 cells, we examined a subpopulation of SCA1+ cells that is present in STOSE cells. Compared to SCA1− cells, SCA1+ STOSE cells have increased colony-forming capacity and form palpable tumors 8 days faster after intrabursal injection into FVB/N mice. This study has identified the STOSE cells as the first spontaneous murine model of HGSC and provides evidence for the OSE as a possible origin of HGSC. Furthermore, this model provides a novel opportunity to study how normal stem-like OSE cells may transform into tumor-initiating cells

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

Identification and prediction of Parkinson's disease subtypes and progression using machine learning in two cohorts.

The clinical manifestations of Parkinson's disease (PD) are characterized by heterogeneity in age at onset, disease duration, rate of progression, and the constellation of motor versus non-motor features. There is an unmet need for the characterization of distinct disease subtypes as well as improved, individualized predictions of the disease course. We used unsupervised and supervised machine learning methods on comprehensive, longitudinal clinical data from the Parkinson's Disease Progression Marker Initiative (n = 294 cases) to identify patient subtypes and to predict disease progression. The resulting models were validated in an independent, clinically well-characterized cohort from the Parkinson's Disease Biomarker Program (n = 263 cases). Our analysis distinguished three distinct disease subtypes with highly predictable progression rates, corresponding to slow, moderate, and fast disease progression. We achieved highly accurate projections of disease progression 5 years after initial diagnosis with an average area under the curve (AUC) of 0.92 (95% CI: 0.95 ± 0.01) for the slower progressing group (PDvec1), 0.87 ± 0.03 for moderate progressors, and 0.95 ± 0.02 for the fast-progressing group (PDvec3). We identified serum neurofilament light as a significant indicator of fast disease progression among other key biomarkers of interest. We replicated these findings in an independent cohort, released the analytical code, and developed models in an open science manner. Our data-driven study provides insights to deconstruct PD heterogeneity. This approach could have immediate implications for clinical trials by improving the detection of significant clinical outcomes. We anticipate that machine learning models will improve patient counseling, clinical trial design, and ultimately individualized patient care