Continuous Survival Research Articles

Prioritizing heart transplantation during the COVID-19 pandemic.

BackgroundCoronavirus disease 2019 (COVID‐19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation‐wide reduction in operative volume. The impact of COVID‐19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID‐19 on a single, large‐volume heart transplant program.MethodsA retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30‐day survival.ResultsFrom March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30‐day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029).ConclusionWe demonstrate that a single, large‐volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID‐19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

A copula-based approach for dynamic prediction of survival with a binary time-dependent covariate.

Dynamic prediction methods incorporate longitudinal biomarker information to produce updated, more accurate predictions of conditional survival probability. There are two approaches for obtaining dynamic predictions: (1) a joint model of the longitudinal marker and survival process, and (2) an approximate approach that specifies a model for a specific component of the joint distribution. In the case of a binary marker, an illness-death model is an example of a joint modeling approach that is unified and produces consistent predictions. However, previous literature has shown that approximate approaches, such as landmarking, with additional flexibility can have good predictive performance. One such approach proposes using a Gaussian copula to model the joint distribution of conditional continuous marker and survival distributions. It has the advantage of specifying established, flexible models for the marginals for which goodness-of-fit can be assessed, and has easy estimation that can be implemented in standard software. In this article, we provide a Gaussian copula approach for dynamic prediction to accommodate a binary marker using a continuous latent variable formulation. We compare the predictive performance of this approach to joint modeling and landmarking using simulations and demonstrate its use for obtaining dynamic predictions in an application to a prostate cancer study.

Impact of African ancestry on the relationship between BMI and survival in early stage breast cancer: Retrospective analysis from E5103.

1010 Background: Both Black race and obesity are associated with worse survival in early stage breast cancer. Obesity disproportionately affects Black women; however, the degree this contributes to racial disparities in breast cancer remains unclear. Prior work evaluated heterogeneous populations or used self- reported race, rather than genetic ancestry. African ancestry is associated with higher BMI and worse survival in breast cancer; however, the intersection between genetic ancestry and obesity on survival outcomes remains unknown. Methods: We analyzed data from the adjuvant trial E5103. Patients with high risk, HER2 negative breast cancer received doxorubicin/cyclophosphamide x 4, followed by weekly paclitaxel x 12, with or without bevacizumab. Genetic ancestry was determined on the 2,854 patients with available germline DNA, BMI, and outcome data using principal components from a genome-wide array. The primary objective assessed impact of BMI on DFS and OS by ancestry. Multivariate Cox proportional hazard models evaluated correlation between continuous or binary BMI and survival in African (AA) and European (EA) Americans. Results: 13.4% of patients were genetically classified as AA and 86.6% as EA. Higher continuous BMI was significantly associated with worse DFS and OS only in AAs (DFS: HR = 1.25 95% CI 1.07-1.46, p = 0.004; OS: HR = 1.38 95% CI 1.10-1.73, p = 0.005); not in EAs (DFS HR = 0.97 95% CI 0.90-1.05, p = 0.50; OS HR = 1.03 95% CI 0.93-1.14, p = 0.52). By disease subtype, BMI was associated with worse outcomes only in AAs with ER+, and not TNBC. By categorical BMI, WHO class III obesity (³ 40) significantly associated with worse DFS and OS only in AAs (DFS HR = 1.98, p = 0.010; OS HR = 2.07, p = 0.064), not in EAs (DFS HR = 0.97, p = 0.86; OS HR = 1.28, p = 0.30). Proportion of African ancestry (proAA) was associated with higher BMI and worse outcomes in the total population; however, within AAs there was no significant interaction between proAA and BMI on DFS (HR = 0.36, p = 0.06) or OS (HR = 0.38, p = 0.24). In AAs, BMI remained associated with DFS (HR = 2.78, p = 0.019), suggesting higher BMI is associated with worse DFS regardless of proAA. Coefficients for the interaction term indicate that as proAA increases the impact of BMI on outcome is lessened. Conclusions: Higher BMI is significantly associated with worse breast cancer outcomes in women of African ancestry in E5103, but not in those of European ancestry. Categorically, this association was significant only for severe obesity, indicating the relationship may depend on the degree of obesity. As proAA increased in AAs, the impact of BMI on outcome was lessened, suggesting other host factors may contribute more to obesity’s influence on outcome than genetics. Determination of the optimal populations for weight loss interventions will advance precision medicine efforts to impact racial disparities and outcomes in early stage breast cancer.

Breast and Lung Effusion Survival Score Models: Improving Survival Prediction in Patients With Malignant Pleural Effusion and Metastasis

Evidence-based guidelines recommend management strategies for malignant pleural effusions (MPEs) based on life expectancy. Existent risk-prediction rules do not provide precise individualized survival estimates. Can a newly developed continuous risk-prediction survival model for patients with MPE and known metastatic disease provide precise survival estimates? Single-center retrospective cohort study of patients with proven malignancy, pleural effusion, and known metastatic disease undergoing thoracentesis from 2014 through 2017. The outcome was time from thoracentesis to death. Risk factors were identified using Cox proportional hazards models. Effect-measure modification (EMM) was tested using the Mantel-Cox test and was addressed by using disease-specific models (DSMs) or interaction terms. Three DSMs and a combined model using interactions were generated. Discrimination was evaluated using Harrell's C-statistic. Calibration was assessed by observed-minus-predicted probability graphs at specific time points. Models were validated using patients treated from 2010 through 2013. Using LENT (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance score, neutrophil-to-lymphocyte ratio and tumor type) variables, we generated both discrete (LENT-D) and continuous (LENT-C) models, assessing discrete vscontinuous predictors' performances. The development and validation cohort included 562 and 727 patients, respectively. The Mantel-Cox test demonstrated interactions between cancer type and neutrophil to lymphocyte ratio (P< .0001), pleural fluid lactate dehydrogenase (P= .029), and bilateral effusion (P= .002). DSMs for lung, breast, and hematologic malignancies showed C-statistics of 0.72, 0.72, and 0.62, respectively; the combined model's C-statistics was 0.67. LENT-D (C-statistic, 0.60) and LENT-C (C-statistic, 0.65) models underperformed. EMM is present between cancer type and other predictors; thus, DSMs outperformed the models that failed to account for this. Discrete risk-prediction models lacked enough precision to be useful for individual-level predictions.

Using PIT-tags and portable antennas for quantification of fish movement and survival in streams under different environmental conditions.

While PIT-tag tracking using mobile antennas is being increasingly used to study fish movement and survival in streams, little is known about the limitations of the method, especially over longer periods of time and under different environmental settings. We used 6 years of data combining tagging, mobile antenna tracking and recaptures of Salmo trutta in multiple small streams in the Lake Lucerne drainage area in Switzerland to evaluate the relative importance of different environmental and intrinsic factors affecting the efficiency of the method. Our study system and experimental design allowed us to accurately verify the continuous presence and survival of recaptured fish in the stream after tracking, which meant that we could estimate detection probability with high confidence. The mean detection probability of tagged trout was 43%, but we found that fish length had a strong negative effect on detection probability, especially in males. Multivariate axes of stream environmental features did not predict efficiency but stream width alone was significantly positively correlated with efficiency. Additionally, stream temperature when tracking had a positive effect on fish detectability. Tag loss at recapture was globally rare (<8%) but common in large postspawn females (>30%). Based on the escape response of fish after detection, we could estimate the proportion of ghost tags, which reached a plateau of around 80% 2 years after tagging. We finally showed that our models of tag loss, fish detection and escape response are needed to interpret detection events. Our results highlight that individual variation in detection probability and tag loss is high and has to be considered for analysis.

Cost-efficient clinical studies with continuous time survival outcomes.

Time-to-event outcomes are common in clinical studies. For example, the time to a first major adverse cardiovascular event (MACE, defined as CVD death, nonfatal myocardial infarction, or stroke) is a commonly used outcome in cardiovascular outcome trials. Owing to the lengthy time frame and other factors, the high costs of conducting such studies has been identified as one of the major obstacles in conducting clinical trials in the United States. However, typical approaches for designing clinical trials with time-to-event outcomes do not consider study costs. For a given effect size (eg, hazard ratio), the power to detect differences between two groups is typically a function of the total number of events observed in the study. Therefore, the same level of power will be achieved based on various combinations of the total number of participants, length of enrollment and total follow-up times, and group allocation probability. Herein, we provide a general framework for designing cost-efficient studies comparing treatments with respect to continuous time-to-event outcomes. Among the various designs that achieve the desired level of power to detect a given effect size for a fixed type-I error level, the optimal cost-efficient design is the design that minimizes the expected total study cost. The method is general and can be used for Cox proportional hazards models or Aalen additive models, and under various recruitment and censoring assumptions. The proposed approach for designing cost-efficient studies is illustrated for a Weibull time-to-event outcome with uniform recruitment and exponentially distributed censoring time. The case of an additive hazards model is also described. A Shiny web application implementation of the proposed methods is presented.

Knock-down of LRP/LR influences signalling pathways in late-stage colorectal carcinoma cells

BackgroundThe 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in several tumourigenic-promoting processes including cellular viability maintenance and apoptotic evasion. Thus, the aim of this study was to assess the molecular mechanism of LRP/LR on apoptotic pathways in late stage (DLD-1) colorectal cancer cells upon siRNA-mediated down-regulation of LRP/LR.MethodssiRNAs were used to down-regulate the expression of LRP/LR in DLD-1 cells which was assessed using western blotting and qPCR. To evaluate the mechanistic role of LRP/LR, proteomic analysis of pathways involved in proliferation and apoptosis were investigated. The data from the study was analysed using a one-way ANOVA, followed by a two-tailed student’s t-test with a confidence interval of 95%.ResultsHere we show that knock-down of LRP/LR led to significant changes in the proteome of DLD-1 cells, exposing new roles of the protein. Moreover, analysis showed that LRP/LR may alter components of the MAPK, p53-apoptotic and autophagic signalling pathways to aid colorectal cancer cells in continuous growth and survival. Knock-down of LRP/LR also resulted in significant decreases in telomerase activity and telomerase-related proteins in the DLD-1 cells.ConclusionsThese findings show that LRP/LR is critically implicated in apoptosis and cell viability maintenance and suggest that siRNA-mediated knock-down of LRP/LR may be a possible therapeutic strategy for the treatment of colorectal cancer.

Treatment Outcomes of Langerhans Cell Histiocytosis: A Retrospective Study.

Background and Objectives: Langerhans cell histiocytosis (LCH) is a rare disease characterized by the infiltration of one or more organs by Langerhans cell-like dendritic cells. LCH often involves the bone, and its clinical evidence is limited. The purpose of this study is to report on the treatment of LCH at our institution and to add to the evidence for LCH. Materials and Methods: We reviewed six cases of LCH treated in our hospital between November 2005 and February 2016. Patient age at the first visit, sex, site of origin, symptoms, image tools used for diagnosis, biopsy site, complications, treatment, and final clinical outcome were evaluated. The median follow-up period was 41 months. Results: The median patient age at the first visit was 13.5 years. Three male and three female individuals were enrolled. Multiple lesions were observed in five cases, and a solitary lesion was observed in one case. Pain was the chief complaint in five cases. Radiography was the most commonly used imaging tool. Bone scintigraphy or magnetic resonance imaging and positron emission tomography-computed tomography were also used to diagnose systematic LCH. Biopsy of the femur was performed in two cases, and biopsy of the tibia, lumbar vertebrae, rib, and radius was performed in one case each. Regarding comorbidities, one case of hepatitis B and one case of autism were observed. Chemotherapy was initiated in two patients. The other four patients were observed naturally. Continuous disease-free survival was observed in five patients. One patient remained alive but not without disease during the final follow-up examination. Conclusion: LCH should be diagnosed as early as possible to treat it appropriately.

UNOS Match Runs for Pediatric Heart Transplant Organ Allocation—How Well Do They Sequence Patients Based on Medical Urgency?

<h3>Purpose</h3> The match run is the automated mechanism by which UNOS prioritizes donor hearts to waitlist candidates for heart transplant (HT) based on medical urgency. We sought to determine how well match runs perform in sequencing patients according to their medical urgency after implementation of the 2016 pediatric heart allocation revisions. <h3>Methods</h3> OPTN data were used to identify all match runs between March 21, 2016 and June 9, 2020 for each pediatric donor heart offered through UNOS to US waitlist candidates. The rank-order of candidates on the match run was compared to the rank-order based on medical urgency alone defined as the probability of survival on the day of the match run using a risk prediction model developed and validated during the prior 6 years. <h3>Results</h3> Overall, 634 donors generated 2,524 unique match runs during the study period when a total of 2,608 candidates were listed for pediatric HT. The median age of donors was 5 years (Q1, Q3, 1, 13), median weight 21 (11, 54) kg with the most common cause of death natural causes (26%), non-motor vehicle accidents (MVA) (22%) and MVA (16%). The risk-prediction model for death or deterioration included 8 variables (age, weight, cardiac diagnosis and cardiac support). When the survival model was applied to the match run candidates within zone, 26% of candidates were ranked out of survival order (i.e. had a rank-reversal) (<b>Table</b>). Of these, 69% of rank-reversals involved candidates <i>within</i> the same UNOS status levels whereas 41% involved candidates spread across UNOS status levels. <h3>Conclusion</h3> There is evidence to suggest that the 2016 revision to the pediatric donor heart allocation system fails to sequence waitlisted candidates according to medical urgency, which affects a substantial fraction of match runs. Misclassification of patient risk by UNOS status level and within UNOS status levels each contribute rank-reversals. Rank-ordering patients based on a continuous survival probability model could address both problems.

Abstract PO-060: Individualized prediction of meningioma recurrence risk over prolonged time periods

Abstract Rationale and purpose: Meningiomas are benign tumors, but significant number of meningiomas display risk of early tumor recurrence. The inter-observer variability among pathologists for grading and some indistinguishable features of meningioma under the microscope prevent accurate prediction of recurrence risk that critically limits appropriate treatment and management of patients who may benefit from adjuvant radiation therapy. We aim to develop individualized prediction of meningioma recurrence risk over prolonged time periods using DNA methylation signatures and other associated clinical factors. Method: The recurrence risk predictor is based on continuous survival random-forest modelling to calculate the probabilities of a recurrence for each meningioma patient over various prolonged time frames. We processed over 500 meningioma samples using our machine-learning model that predicts probability of tumor recurrence based on methylation data. We used Random Forest based Rangers package as the survival model that returns the probabilities of a recurrence not happening over various prolonged time frames. Result: Methylation-based predictor distinguishes high-low risk groups over prolonged time periods. The predictor was validated using external validation cohort based on the selected probes and original training model. We found that methylation based predictor has potential to identify in patients with grade II meningiomas especially, while it also can identify grade I patients with higher recurrence risk over prolonged time periods. Conclusion: There were limitations of standard of care classifications in meningioma especially for Grade 2 patients due to significant intra- and inter-observer variability for grading and selection of patients for treatment. The individualized risk predictor can help determining the decisions regarding adjuvant radiation treatment versus observation along for each meningioma patient in the clinic. Citation Format: Yasin Mamatjan, Farshad Nassiri, Mira Salih, Kenneth Aldape, Gelareh Zadeh. Individualized prediction of meningioma recurrence risk over prolonged time periods [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-060.

Hypothetical novel simulations to explain the evolutionary survival of the hypo-reproductive extreme tail in the complex human diversity

Hierarchical structures which lie hidden between human complex conditions and reproductivity cannot be simple, and trends of each population component does not necessarily pertain to evolutionary theories. As an illustration, the fitness of individuals with heritable extreme conditions can be low across continuing generations in observational data. Autism and schizophrenia are characterized by such evolutionary paradox of survival and hypo-reproductivity in the complex human diversity. Theoretical mechanisms for the observational fact were evaluated using a simple formula which was established to simulate stochastic epistasis-mediated phenotypic diversity. The survival of the hypo-reproductive extreme tail could be imitated just by the predominant presence of stochastic epistasis mechanism, suggesting that stochastic epistasis might be a genetic prerequisite for the evolutionary paradox. As supplemental cofactors of stochastic epistasis, a random link of the extreme tail to both un- and hyper-reproductivity and group assortative mating were shown to be effective for the paradox. Especially, the mixed localization of un- and hyper-reproductivity in the tail of a generational population evidently induced the continuous survival of outliers and extremes. These hypothetical considerations and mathematical simulations may suggest the significance of stochastic epistasis as the essential genetic background of complex human diversity.

Factors Associated with Biofilm Persistence on Different Surfaces, Spread and Pathogenicity

The conglomeration of microbial life on a self-produced extracellular polysaccharide (EPS) matrix for mutual co-existence and protection against external aggression and adverse environmental conditions best describe biofilms. This community of microorganisms confers a number of survival and nutritional benefits to members while at the same time portend great ecological and health concern. Biofilms can form on virtually any surface; terrestrial, aquatic, plants, animals and on medical devices and implants. The ability of biofilms to disperse from the parental stalk ensures continuous survival and spread within their ecological niche. Biofilm organisms therefore possess unique survival mechanisms over their plancktonic form and have contributed to our understanding of the mechanisms of pathogenicity of infectious microorganisms. This review highlights trends in the understanding of biofilms and emphasized their health significance.

Berberine inhibited metastasis through miR-145/MMP16 axis in vitro

Ovarian cancer is the first leading cause of death in gynecological cancers. The continuous survival and metastasis of cancer cells are the main causes of death and poor prognosis in patients with ovarian cancer. Berberine is an effective component extracted from the rhizomes of coptis chinensis and phellodendron chinensis. In our study, we aim to explore the molecular mechanism underlying the regulation of proliferation, migration and invasion by berberine in ovarian cancer cells. CCK8 assay was used for detection of proliferative capacity of SKOV3 and 3AO cells. Wound healing assay was used to estimate cell migration and transwell assay was used to assess cell invasion. The mRNA expression of miR-145 and MMP16 were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of MMP16 was detected by western blot analysis. In addition, luciferase reporter assays were used to demonstrate MMP16 was a target of miR-145. The results demonstrated berberine inhibited proliferation, migration and invasion, promoted miR-145 expression, and decreased MMP16 expression in SKOV3 and 3AO cells. MMP16 was a target of miR-145. Moreover, downregulation of MMP16 contributed to the inhibition of proliferation, migration and invasion by berberine. Together, our results revealed that berberine inhibited proliferation, migration and invasion through miR-145/MMP16 in SKOV3 and 3AO cells, highlighting the potentiality of berberine to be used as a therapeutic agent for ovarian cancer.

Audit Socialization and Professional Success: Evidence from Thailand

The objective of this study is to examine the effects of audit socialization and professional commitment on professional success of tax auditors in Thailand through individual learning as the moderator. The specific research questions are: (1) How audit socialization affects professional commitment, (2) How professional commitment influences professional success, and (3) How individual learning moderates the audit socialization-professional commitment relationships, the audit socialization-professional success relationships, and the professional commitment-professional success relationships. This study collected data from 249 tax auditors in Thailand by using questionnaire. To investigate the research relationships, both structural equation model and multiple regression analysis are implemented. Within the research results, audit socialization has a significant positive effect on professional commitment and professional success while professional commitment has an important positive influence on professional success. Similarly, individual learning positively moderates the professional commitment-professional success relationships. In summary, audit socialization is important for auditing professions and it is a key determinant of professional success. Thus, auditors need to pay attention to audit socialization through learning and understanding it and applying its concepts to audit works to increase auditors' professional success, continuous survival and long-term sustainability.

A new risk‐adjusted EWMA control chart based on survival time for monitoring surgical outcome quality

AbstractMonitoring surgical outcome quality by risk‐adjusted control charts has attracted wide attention. The hidden medical errors may cause increasing of adverse events such as infection, rehospitalization, and even death. Quickly and timely detecting abnormal changes of surgical performance helps reduce the probability of adverse events and improve health care quality. Most existing monitoring schemes focus on the binary surgical outcomes. However, continuous survival times of patients should be considered for more accurate monitoring. In this paper, a new exponentially weighted moving average (EWMA) control chart is proposed for monitoring continuous surgical outcomes. To describe surgical performance, a patient's actual survival time and predicted mortality are combined in an illustrative and interpretable way. Performance of the proposed chart is evaluated with different chart parameters under different shifts by a simulation study. We compare our chart with the risk‐adjusted survival time cumulative sum chart, and the simulation results demonstrate that the proposed monitoring scheme has better efficiency. The implementation of the proposed chart is illustrated by a real example. Besides an analysis of the entire dataset, the surgical performance of each surgeon is monitored, because each of them has patients with different risk levels.

Prospective Karyotype Analysis in Adult Acute Lymphoblastic Leukemia: The Cancer and Leukemia Group B Experience

AbstractThe Cancer and Leukemia Group B (CALGB) has been conducting a prospective cytogenetic companion study (CALGB 8461) to all CALGB treatment protocols for newly diagnosed adults with acute lymphoblastic leukemia (ALL). These protocols underwent a significant change in 1988 when a new intensive chemotherapy program was introduced (CALGB 8811). We asked whether karyotype continued to represent a significant prognostic factor in adult ALL patients after the change. A total of 256 patients had adequate pretreatment cytogenetic analyses: 67 before 1988 and 189 subsequently. The complete remission (CR) rate for the whole group was 80%. Patients with t(9;22), t(4;11), −7, or +8 had significantly lower probabilities of continuous CR and survival at 5 years (.11 and .12) than patients with a normal karyotype (.38 and .37) and patients with miscellaneous cytogenetic abnormalities (.52 and .49;P < .001 for each comparison). When analyzed by treatment period, the CR rate before CALGB 8811 was 63%; subsequently, it was 86% (P < .001). Patients with cytogenetic abnormalities other than t(9;22), t(4;11), −7, or +8 had better CR rates, disease-free survival (DFS), and survivals (P = .001,P = .04, and P = .004, respectively) after the change to the more intensive chemotherapy regimens. Patients with normal cytogenetics had improved CR rate but no improved DFS or survival, whereas no significant benefit for patients with t(9;22), t(4;11), −7, or +8 was seen. In a multivariate analysis, karyotype retained its prognostic significance for DFS but not for survival; it remained the most important factor for DFS. We conclude that cytogenetic analysis at diagnosis should be used to guide treatment decisions in adults with ALL.

Bioaccumulation of heavy metals and their toxicity assessment in Mystus species.

This study was conducted on two native fish species namely Mystus vittatus and Mystus tengara inhabiting challenging environment of Yamuna River. The heavy metals concentrations in the river water were found to be as follows: Fe > Mn > Zn > Cu > Ni > Cr > Cd, all above the Bureau of Indian Standards (BIS) and World Health Organization (WHO) guidelines. The high metal pollution index in gill, liver, and kidney of M. vittatus was recorded compared to M. tengara. The pathology caused by the accumulation of heavy metals resulted significantly (p < 0.05) higher enzyme activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine kinase (CK) in M. tengara as compared to M. vittatus. However, albumin: globulin ratio was found to be below 0.8 in both fishes. Higher total leukocyte (TLC) (48.5 × 103/mm3), lymphocytes (40%), respiratory burst activity (1.9), and nitric oxide synthase (NOS) activity (13.11 U/L) in M. vittatus reflect high immune response. In addition, chromosomal breakage study showed significantly (p < 0.05) low micronuclei frequency, lobed nuclei, and kidney-shaped nuclei (KSN) in M. vittatus. These results indicate that under the same challenging conditions M. vittatus have more capability of resistance and its continuous survival points towards its suitability to serve as a bioindicator than M. tengara.

On the hysteresis of financial crises in the US: Evidence from S&P 500

This paper examines the financial crisis durations in the US. Based on S&P 500 returns we investigate whether these crises exhibit long-memory or are merely transitional. To this end, we rely on continuous survival time models to gauge the hazard of ending a spell of contiguous return declines and test several specifications under the proportional hazards and the accelerated failure time assumptions. Our findings suggest that the log-normal accelerated failure time is the best model to describe the data, thus yielding a non-monotonic hazard that increases up to a maximum and, then decreases. We also found that spell lengths increase during recessions, when interest rates and prices are more volatile. Our main conclusion is that short spells of negative returns are mainly frictional, while long spells turn into structural crises that may trigger hysteresis.

Abstract PO-172: Impact of African ancestry on the relationship between body mass index (BMI) and survival in early stage breast cancer: Retrospective analysis from E5103

Abstract Purpose: Both African American (AA) race and obesity are associated with worse survival in early stage breast cancer. Obesity disproportionately affects AA women, and may further racial disparities in breast cancer. Prior work investigating the intersection of race, BMI, and outcome in the large adjuvant trial E1199 found obesity to be prognostic of worse survival in White patients, with no significant impact on the disparately inferior survival outcomes seen in Black patients. However, this analysis was based on self-reported race, which neglects underlying genetic ancestry that may drive biologic differences. Here, we investigate the impact of BMI on outcomes in patients of African or European ancestry in the phase III adjuvant breast cancer trial E5103. Methods: E5103 enrolled patients with high risk, HER2 negative, early stage breast cancer to receive adjuvant doxorubicin and cyclophosphamide for 4 cycles, followed by 12 weeks of weekly paclitaxel, with or without bevacizumab. Genetic ancestry was determined on the 3,373 patients with available germline DNA, BMI, and outcome data using principal components from a genome-wide array. The primary objective was to assess the impact of BMI on disease free survival (DFS) and overall survival (OS) by ancestry. A univariate Cox proportional hazard model was used to evaluate the correlation between continuous or binary BMI and survival in AA or European Americans (EA). Results: 11.6% (n=390) of patients were genetically classified as AA and 74.6% (n=2517) as EA. Higher BMI (increment of every 5 kg/m2) was significantly associated with worse DFS (HR=1.24, p=0.006) and OS (HR=1.38, p=0.005) only in AAs, but not in EAs (DFS p=0.76, OS p=0.35). Exploring BMI categories in AAs, survival differences were most significant between patients who had morbid obesity (BMI ≥40) and those who did not (DFS HR= 2.01, p=0.009; OS HR=2.19, p=0.045). However, in EAs, even morbid obesity was not associated with survival (DFS p=0.89, OS p=0.31). In the ER+ sub-population, BMI was associated with both DFS (HR=1.29, p=0.032) and OS (HR=1.60, p=0.017) in AAs, but only with OS in EAs (HR=1.15, p=0.049). In the triple negative sub-population, there was a trend toward worse survival with increasing BMI in AAs (p=0.098), but not in EAs (p=0.62). Conclusion: In contrast to prior work based on self-reported race, we found BMI to be significantly associated with worse survival in women of African ancestry in E5103, a large adjuvant trial that reflects our current approach to curative systemic therapy in breast cancer. Categorically, this association was significant only for morbid obesity, suggesting the relationship between BMI, race, and outcome may depend on the degree of obesity. Genetic ancestry may explain biologic differences driving both higher BMI and worse outcomes resulting in racial disparities in breast cancer. Citation Format: Tarah J. Ballinger, Guanglong Jiang, Fei Shen, Kathy D. Miller, Bryan P. Schneider. Impact of African ancestry on the relationship between body mass index (BMI) and survival in early stage breast cancer: Retrospective analysis from E5103 [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-172.

A Method to Improve Continuous Renal Replacement Therapy Circuit Survival Time in Critically Ill Coronavirus Disease 2019 Patients With Acute Kidney Injury.

Optimizing continuous renal replacement therapy circuit survival in coronavirus disease 2019 patients admitted to the ICU. Single-center prospective observational cohort study. Tertiary academic teaching ICU. Between March 19, 2020, and May 18, 2020, 11 out of 101 coronavirus disease 2019 patients were treated with continuous renal replacement therapy comprising 127 continuous renal replacement therapy days. A nonrandomized observational comparison of circuit anticoagulation modalities using standard regional citrate anticoagulation, continuous IV heparin anticoagulation, or the combination of regional citrate anticoagulation with either continuous IV heparin or therapeutic dose nadroparin. Circuit patency was shorter than 24 hours using standard regional citrate anticoagulation or continuous IV heparin anticoagulation. Median circuit survival increased with at least 165% when the combination of regional citrate anticoagulation with either continuous IV heparin or therapeutic dose nadroparin was applied. Continuous renal replacement therapy circuit patency is diminished in coronavirus disease 2019 ICU patients. Combining regional citrate anticoagulation with either continuous IV heparin or therapeutic dose nadroparin increases filter survival as compared with regional citrate anticoagulation alone in this nonrandomized observational study.