Objective: We explored whether use of deep learning to model temporal relations among events in electronic health records (EHRs) would improve model performance in predicting initial diagnosis of ...heart failure (HF) compared to conventional methods that ignore temporality.
Materials and Methods: Data were from a health system’s EHR on 3884 incident HF cases and 28 903 controls, identified as primary care patients, between May 16, 2000, and May 23, 2013. Recurrent neural network (RNN) models using gated recurrent units (GRUs) were adapted to detect relations among time-stamped events (eg, disease diagnosis, medication orders, procedure orders, etc.) with a 12- to 18-month observation window of cases and controls. Model performance metrics were compared to regularized logistic regression, neural network, support vector machine, and K-nearest neighbor classifier approaches.
Results: Using a 12-month observation window, the area under the curve (AUC) for the RNN model was 0.777, compared to AUCs for logistic regression (0.747), multilayer perceptron (MLP) with 1 hidden layer (0.765), support vector machine (SVM) (0.743), and K-nearest neighbor (KNN) (0.730). When using an 18-month observation window, the AUC for the RNN model increased to 0.883 and was significantly higher than the 0.834 AUC for the best of the baseline methods (MLP).
Conclusion: Deep learning models adapted to leverage temporal relations appear to improve performance of models for detection of incident heart failure with a short observation window of 12–18 months.
Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the organism can develop after ingestion of contaminated food products. Small and ...large outbreaks of listeriosis have been described. Listeria monocytogenes can cause a number of clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. The latter syndrome mimics the veterinary infection in ruminants called "circling disease". Neonatal infection can occur as a result of maternal chorioamnionitis ("early onset" sepsis) or through passage through a birth canal colonized with Listeria from the gastrointestinal tract. ("late onset" meningitis). Treatment of listeriosis is usually with a combination of ampicillin and an aminoglycoside but other regimens have been used. The mortality rate is high, reflecting the combination of an immunocompromised host and an often delayed diagnosis.
Despite the millions of dollars spent on target validation and drug optimization in preclinical models, most therapies still fail in phase III clinical trials. Our current model systems, or the way ...we interpret data from them, clearly do not have sufficient clinical predictive power. Current opinion suggests that this is because the cell lines and xenografts that are commonly used are inadequate models that do not effectively mimic and predict human responses. This has become such a widespread belief that it approaches dogma in the field of drug discovery and optimization and has spurred a surge in studies devoted to the development of more sophisticated animal models such as orthotopic patient-derived xenografts in an attempt to obtain more accurate estimates of whether particular cancers will respond to given treatments. Here, we explore the evidence that has led to the move away from the use of in vitro cell lines and toward various forms of xenograft models for drug screening and development. We review some of the pros and cons of each model and give an overview of ways in which the use of cell lines could be modified to improve the predictive capacity of this well-defined model.
Most contemporary civil wars are now recurrences of earlier civil wars. In contrast to classic theories of grievance and opportunity, this article advances a theory of civil war recurrence that ...highlights the critical role political and legal institutions play in constraining elites in post–civil war states. Such constraints serve as a check on executive power, help incumbent elites credibly commit to political reform, and create a situation where rebels need not maintain militias as a supplementary mechanism to hold political elites in line. All of this reduces the odds of repeat civil war. Using a statistical analysis of post-conflict years, this article demonstrates that strong political institutions are not only significantly and negatively related to repeat civil war but are the primary determinants of whether countries get caught in the conflict trap.
The number of radical Islamist groups fighting in civil wars in Muslim countries has steadily grown over the last twenty years, with such groups outlasting and outperforming more moderate groups. By ...2016, Salafi jihadist groups accounted for most of the militant groups in Syria and half of such groups in Somalia. In Iraq, a third of all militant groups were composed of Salafi jihadists. Many analysts argue that the rise of these groups reflects an increase in radical beliefs in Muslim societies. Under certain conditions, however, rebel leaders have strong incentives to embrace an extreme ideology even if they do not believe the ideas that underlie it. When competition is high, information is poor, and institutional constraints are weak, an extremist ideology can help rebel leaders overcome difficult collective-action, principal-agent, and commitment problems. All three of these conditions have been present in the post-2003 civil wars in the Middle East and Africa, and all help explain the emergence and growth of radical groups such as the Islamic State and al-Qaida.
Gravity models are powerful tools for mapping tectonic structures, especially in the deep ocean basins where the topography remains unmapped by ships or is buried by thick sediment. We combined new ...radar altimeter measurements from satellites CryoSat-2 and Jason-1 with existing data to construct a global marine gravity model that is two times more accurate than previous models. We found an extinct spreading ridge in the Gulf of Mexico, a major propagating rift in the South Atlantic Ocean, abyssal hill fabric on slow-spreading ridges, and thousands of previously uncharted seamounts. These discoveries allow us to understand regional tectonic processes and highlight the importance of satellite-derived gravity models as one of the primary tools for the investigation of remote ocean basins.
The mammalian Slc4 (Solute carrier 4) family of transporters is a functionally diverse group of 10 multi-spanning membrane proteins that includes three Cl-HCO3 exchangers (AE1-3), five Na(+)-coupled ...HCO3(-) transporters (NCBTs), and two other unusual members (AE4, BTR1). In this review, we mainly focus on the five mammalian NCBTs-NBCe1, NBCe2, NBCn1, NDCBE, and NBCn2. Each plays a specialized role in maintaining intracellular pH and, by contributing to the movement of HCO3(-) across epithelia, in maintaining whole-body pH and otherwise contributing to epithelial transport. Disruptions involving NCBT genes are linked to blindness, deafness, proximal renal tubular acidosis, mental retardation, and epilepsy. We also review AE1-3, AE4, and BTR1, addressing their relevance to the study of NCBTs. This review draws together recent advances in our understanding of the phylogenetic origins and physiological relevance of NCBTs and their progenitors. Underlying these advances is progress in such diverse disciplines as physiology, molecular biology, genetics, immunocytochemistry, proteomics, and structural biology. This review highlights the key similarities and differences between individual NCBTs and the genes that encode them and also clarifies the sometimes confusing NCBT nomenclature.
Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO
) and water (H
O) into bicarbonate (HCO
) and protons (H
). These enzymes impact ...numerous physiological processes that occur within and across the many compartments in the body. Within compartments, CAs promote rapid H
buffering and thus the stability of pH-sensitive processes. Between compartments, CAs promote movements of H
, CO
, HCO
, and related species. This traffic is central to respiration, digestion, and whole-body/cellular pH regulation. Here, we focus on the role of mathematical modeling in understanding how CA enhances buffering as well as gradients that drive fluxes of CO
and other solutes (facilitated diffusion). We also examine urinary acid secretion and the carriage of CO
by the respiratory system. We propose that the broad physiological impact of CAs stem from three fundamental actions: promoting H
buffering, enhancing H
exchange between buffer systems, and facilitating diffusion. Mathematical modeling can be a powerful tool for: (1) clarifying the complex interdependencies among reaction, diffusion, and protein-mediated components of physiological processes; (2) formulating hypotheses and making predictions to be tested in wet-lab experiments; and (3) inferring data that are impossible to measure.
Abstract
This paper provides an update of our previous scaling relations between galaxy-integrated molecular gas masses, stellar masses, and star formation rates (SFRs), in the framework of the star ...formation main sequence (MS), with the main goal of testing for possible systematic effects. For this purpose our new study combines three independent methods of determining molecular gas masses from CO line fluxes, far-infrared dust spectral energy distributions, and ∼1 mm dust photometry, in a large sample of 1444 star-forming galaxies between
z
= 0 and 4. The sample covers the stellar mass range log(
M
*
/
M
⊙
) = 9.0–11.8, and SFRs relative to that on the MS,
δ
MS = SFR/SFR(MS), from 10
−1.3
to 10
2.2
. Our most important finding is that all data sets, despite the different techniques and analysis methods used, follow the same scaling trends, once method-to-method zero-point offsets are minimized and uncertainties are properly taken into account. The molecular gas depletion time
t
depl
, defined as the ratio of molecular gas mass to SFR, scales as (1 +
z
)
−0.6
× (
δ
MS)
−0.44
and is only weakly dependent on stellar mass. The ratio of molecular to stellar mass
μ
gas
depends on (
1
+
z
)
2.5
×
(
δ
MS
)
0.52
×
(
M
*
)
−
0.36
, which tracks the evolution of the specific SFR. The redshift dependence of
μ
gas
requires a curvature term, as may the mass dependences of
t
depl
and
μ
gas
. We find no or only weak correlations of
t
depl
and
μ
gas
with optical size
R
or surface density once one removes the above scalings, but we caution that optical sizes may not be appropriate for the high gas and dust columns at high
z
.
PDF
