Correcting for Selection Bias and Missing Response in Regression using Privileged Information

When estimating a regression model, we might have data where some labels are missing, or our data might be biased by a selection mechanism. When the response or selection mechanism is ignorable (i.e., independent of the response variable given the features) one can use off-the-shelf regression methods; in the nonignorable case one typically has to adjust for bias. We observe that privileged data (i.e. data that is only available during training) might render a nonignorable selection mechanism ignorable, and we refer to this scenario as Privilegedly Missing at Random (PMAR). We propose a novel imputation-based regression method, named repeated regression, that is suitable for PMAR. We also consider an importance weighted regression method, and a doubly robust combination of the two. The proposed methods are easy to implement with most popular out-of-the-box regression algorithms. We empirically assess the performance of the proposed methods with extensive simulated experiments and on a synthetically augmented real-world dataset. We conclude that repeated regression can appropriately correct for bias, and can have considerable advantage over weighted regression, especially when extrapolating to regions of the feature space where response is never observed

Strategic Debt: Evidence from Bertrand and Cournot Competition

We investigate how competitive behavior affects the capital structure of a firm. Theory predicts that the impact of different types of output market uncertainty (in particular, unanticipated shocks in demand and costs) on a firm’s leverage depends on the type of competition in an industry. We test these predictions in a sample of U.S. manufacturing firms by classifying firms into Cournot competition (strategic substitutes), and Bertrand competition (strategic complements). We show that demand uncertainty is positively related to leverage for firms in both the Cournot and the Bertrand sample. Cost uncertainty has a significantly positive impact on the leverage of Cournot firms, but plays a negligible role for Bertrand firms. Our results support the strategic use of debt and highlight the role of firms’ competitive behavior in the product market in their capital structure decisions

Role of bladder cancer metabolic reprogramming in the effectiveness of immunotherapy

Metabolic reprogramming (MR) is an upregulation of biosynthetic and bioenergetic pathways to satisfy increased energy and metabolic building block demands of tumors. This includes glycolytic activity, which deprives the tumor microenvironment (TME) of nutrients while increasing extracellular lactic acid. This inhibits cytotoxic immune activity either via direct metabolic competition between cancer cells and cytotoxic host cells or by the production of immune-suppressive metabolites such as lactate or kynurenine. Since immunotherapy is a major treatment option in patients with metastatic urothelial carcinoma (UC), MR may have profound implications for the success of such therapy. Here, we review how MR impacts host immune response to UC and the impact on immunotherapy response (including checkpoint inhibitors, adaptive T cell therapy, T cell activation, antigen presentation, and changes in the tumor microenvironm

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy

Background: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. Objective: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. Methods: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. Results: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%–3.6%] vs 2.6% [2.1%–6.4%], P = .541; CB: 1.7% [0.9%–3.1%] vs 1.5% [0.5%–2.8%], P = .600; LVA: 4.7% [1.6%–7.7%] vs 2.9% [2.1%–7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. Conclusion: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population

Biatrial arrhythmogenic substrate in patients with hypertrophic obstructive cardiomyopathy

Background: Atrial fibrillation (AF) in patients with hypertrophic obstructive cardiomyopathy (HOCM) may be caused by a primary atrial myopathy. Whether HOCM-related atrial myopathy affects mainly electrophysiological properties of the left atrium (LA) or also the right atrium (RA) has never been investigated. Objective: The purpose of this study was to characterize atrial conduction and explore differences in the prevalence of conduction disorders, potential fractionation, and low-voltage areas (LVAs) between the RA and LA during sinus rhythm (SR) as indicators of potential arrhythmogenic areas. Methods: Intraoperative epicardial mapping of both atria during SR was performed in 15 HOCM patients (age 50 ± 12 years). Conduction delay (CD) and conductin block (CB), unipolar potential characteristics (voltages, fractionation), and LVA were quantified. Results: Conduction disorders and LVA were found scattered throughout both atria in all patients and did not differ between the RA and LA (CD: 2.9% [1.9%–3.6%] vs 2.6% [2.1%–6.4%], P = .541; CB: 1.7% [0.9%–3.1%] vs 1.5% [0.5%–2.8%], P = .600; LVA: 4.7% [1.6%–7.7%] vs 2.9% [2.1%–7.1%], P = .793). Compared to the RA, unipolar voltages of single potentials (SPs) and fractionated potentials (FPs) were higher in the LA (SP: P75 7.3 mV vs 10.9 mV; FP: P75 2.0 mV vs 3.7 mV). FP contained low-voltage components in only 18% of all LA sites compared to 36% of all RA sites. Conclusion: In patients with HOCM, conduction disorders, LVA, and FP are equally present in both atria, supporting the hypothesis of a primary atrial myopathy. Conceptually, the presence of a biatrial substrate and high-voltage FP may contribute to failure of ablative therapy of atrial tachyarrhythmias in this population

In-vivo Sino-Atrial Node Mapping in Children and Adults With Congenital Heart Disease

BACKGROUND: Sinus node dysfunction (SND) and atrial tachyarrhythmias frequently co-exist in the aging patient with congenital heart disease (CHD), even after surgical correction early in life. We examined differences in electrophysiological properties of the sino-atrial node (SAN) area between pediatric and adult patients with CHD. METHODS: Epicardial mapping of the SAN was performed during sinus rhythm in 12 pediatric (0.6 [0.4–2.4] years) and 15 adult (47 [40–55] years) patients. Unipolar potentials were classified as single-, short or long double- and fractionated potentials. Unipolar voltage, relative R-to-S-amplitude ratio and duration of all potentials was calculated. Conduction velocity (CV) and the amount of conduction block (CB) was calculated. RESULTS: SAN activity in pediatric patients was solely observed near the junction of the superior caval vein and the right atrium, while in adults SAN activity was observed even up to the middle part of the right atrium. Compared to pediatric patients, the SAN region of adults was characterized by lower CV, lower voltages, more CB and a higher degree of fractionation. At the earliest site of activation, single potentials from pediatrics consisted of broad monophasic S-waves with high amplitudes, while adults had smaller rS-potentials with longer duration which were more often fractionated. CONCLUSIONS: Compared to pediatric patients, adults with uncorrected CHD have more inhomogeneous conduction and variations in preferential SAN exit site, which are presumable caused by aging related remodeling. Long-term follow-up of these patients is essential to demonstrate whether these changes are related to development of SND and also atrial tachyarrhythmias early in life

A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML

Cancer initiation is orchestrated by an interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted single-cell RNA sequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPC) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR + stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow. Inflammatory niche remodeling and the resulting deprivation of critical HSPC regulatory factors are predicted to repress high-output hematopoietic stem cell subsets in NPM1-mutated acute myeloid leukemia (AML), with relative resistance of clonal cells. Stromal gene signatures reflective of niche remodeling are associated with reduced relapse rates and favorable outcomes after chemotherapy across all genetic risk categories. Elucidation of the intercellular signaling defining human AML, thus, predicts that inflammatory remodeling of stem cell niches drives tissue repression and clonal selection but may pose a vulnerability for relapse-initiating cells in the context of chemotherapeutic treatment.</p

Modeling blue to UV upconversion in B-NaYF4:Tm3+

Samples of 0.01% and 0.3% Tm3+-doped b-NaYF4 show upconverted UV luminescence at 27 660 cm1 (361 nm) after blue excitation at 21 140 cm1 (473 nm). Contradictory upconversion mechanisms in the literature are reviewed and two of them are investigated in detail. Their agreement with emission and two-color excitation experiments is examined and compared. Decay curves are analyzed using the Inokuti?Hirayama model, an average rate equation model, and a microscopic rate equation model that includes the correct extent of energy transfer. Energy migration is found to be negligible in these samples, and hence the average rate equation model fails to correctly describe the decay curves. The microscopic rate equation model accurately fits the experimental data and reveals the strength and multipolarity of various interactions. This microscopic model is able to determine the most likely upconversion mechanism