Parity Calibration

In a sequential regression setting, a decision-maker may be primarily concerned with whether the future observation will increase or decrease compared to the current one, rather than the actual value of the future observation. In this context, we introduce the notion of parity calibration, which captures the goal of calibrated forecasting for the increase-decrease (or "parity") event in a timeseries. Parity probabilities can be extracted from a forecasted distribution for the output, but we show that such a strategy leads to theoretical unpredictability and poor practical performance. We then observe that although the original task was regression, parity calibration can be expressed as binary calibration. Drawing on this connection, we use an online binary calibration method to achieve parity calibration. We demonstrate the effectiveness of our approach on real-world case studies in epidemiology, weather forecasting, and model-based control in nuclear fusion.Comment: To appear at UAI 2023; 19 pages and 10 figure

Correcting for heterogeneity in real-time epidemiological indicators

Auxiliary data sources have become increasingly important in epidemiological surveillance, as they are often available at a finer spatial and temporal resolution, larger coverage, and lower latency than traditional surveillance signals. We describe the problem of spatial and temporal heterogeneity in these signals derived from these data sources, where spatial and/or temporal biases are present. We present a method to use a ``guiding'' signal to correct for these biases and produce a more reliable signal that can be used for modeling and forecasting. The method assumes that the heterogeneity can be approximated by a low-rank matrix and that the temporal heterogeneity is smooth over time. We also present a hyperparameter selection algorithm to choose the parameters representing the matrix rank and degree of temporal smoothness of the corrections. In the absence of ground truth, we use maps and plots to argue that this method does indeed reduce heterogeneity. Reducing heterogeneity from auxiliary data sources greatly increases their utility in modeling and forecasting epidemics

Restaurants at the Crossroads: A State By State Summary of Key Wage-and-Hour Provision Affecting the Restaurant Industry

Restaurateurs face a remarkable tangle of laws and regulations that on their face are meant to protect workers, but which often serve to create a confusion for operators—and employment for labor attorneys. While many states simply apply federal wage and hour laws, others have been active in passing their own statutes, which set regulations that are more stringent than those of the federal government. Based on discussions at Cornell Legal Roundtables, this tool presents a comprehensive compilation of the wage-and-hour rules from all fifty U.S. states, plus the District of Columbia and Commonwealth of Puerto Rico. While this tool does not substitute for the advice of legal counsel, it provides an overview of regulations to guide restaurateurs as they set their human resource policies and procedures

Statistical-mechanical theory of ultrasonic absorption in molecular liquids

We present results of theoretical description of ultrasonic phenomena in molecular liquids. In particular, we are interested in the development of microscopical, i.e., statistical-mechanical framework capable to explain the long living puzzle of the excess ultrasonic absorption in liquids. Typically, ultrasonic wave in a liquid can be generated by applying the periodically alternating external pressure with the angular frequency that corresponds to the ultrasound. If the perturbation introduced by such process is weak - its statistical-mechanical treatment can be done with the use of the linear response theory. We treat the liquid as a system of interacting sites, so that all the response/aftereffect functions as well as the energy dissipation and generalized (wave-vector and frequency dependent) ultrasonic absorption coefficient are obtained in terms of familiar site-site static and time correlation functions such as static structure factors or intermediate scattering functions. To express the site-site intermediate scattering functions we refer to the site-site memory equations in the mode-coupling approximation for the first-order memory kernels, while equilibrium properties such as site-site static structure factors, direct and total correlation functions are deduced from the integral equation theory of molecular liquids known as RISM or one of its generalizations. All the formalism is phrased in a general manner, hence the obtained results are expected to work for arbitrary type of molecular liquid including simple, ionic, polar, and non-polar liquids.Comment: 14 pages, 1 eps-figure, RevTeX4-forma

Disposable Nafion-Coated Single-Walled Carbon Nanotube Test Strip for Electrochemical Quantitative Determination of Acetaminophen in a Finger-Prick Whole Blood Sample

A disposable electrochemical test strip for the quantitative point-of-care (POC) determination of acetaminophen (paracetamol) in plasma and finger-prick whole blood was fabricated. The industrially scalable dry transfer process of single-walled carbon nanotubes (SWCNTs) and screen printing of silver were combined to produce integrated electrochemical test strips. Nafion coating stabilized the potential of the Ag reference electrode and enabled the selective detection in spiked plasma as well as in whole blood samples. The test strips were able to detect acetaminophen in small 40 mu L samples with a detection limit of 0.8 mu M and a wide linear range from 1 mu M to 2 mM, well within the required clinical range. After a simple 1:1 dilution of plasma and whole blood, a quantitative detection with good recoveries of 79% in plasma and 74% in whole blood was achieved. These results strongly indicate that these electrodes can be used directly to determine the unbound acetaminophen fraction without the need for any additional steps. The developed test strip shows promise as a rapid and simple POC quantitative acetaminophen assay.Peer reviewe

A systems toxicology paracetamol overdose framework: accounting for high-risk individuals

The most commonly prescribed painkiller worldwide, paracetamol (acetaminophen, APAP) is also the predominant cause of acute liver failure (ALF), and therefore paracetamol-induced liver toxicity remains an important clinical problem. The standard clinical treatment framework for paracetamol overdose currently allows for antidote therapy decisions to be made based on a nomogram treatment line. This treatment threshold is lowered for patients adjudged to be highly susceptible to liver injury due to risk factors such as anorexia nervosa or bulimia. Additionally, both the original and adjusted clinical frameworks are highly dependent on knowledge from the patient regarding time since ingestion and initial dose amount, both of which are often highly unpredictable. We have recently developed a pre-clinical framework for predicting time since ingestion, initial dose amount and subsequent probability of liver injury based on novel biomarker concentrations. Here, we use identifiability analysis as a tool to increase confidence in our model parameter estimates and extend the framework to make predictions for both healthy and high-risk populations. Through pharmacokinetic-pharmacodynamic model refinement, we identify thresholds that determine whether necrosis or apoptosis is the dominant form of cell death, which can be essential for effective ALF interventions. Using a single blood test, rather than the multiple tests required in the current clinical frameworks, our model provides overdose identification information applicable for healthy and high-risk individuals as well as quantitative measures of estimated liver injury probability

Systems Toxicology Approach to Identifying Paracetamol Overdose

Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable. A pharmacokinetic/pharmacodynamic (PK/PD) APAP model has been built in order to understand the relationships between a panel of biomarkers and APAP dose. Visualization and statistical tools have been used to predict initial APAP dose and time since administration. Additionally, logistic regression analysis has been applied to histology data to provide a prediction of the probability of liver injury

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase (JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death