Predicting pharmaceutical particle size distributions using kernel mean embedding

In the pharmaceutical industry, the transition to continuous manufacturing of solid dosage forms is adopted by more and more companies. For these continuous processes, high-quality process models are needed. In pharmaceutical wet granulation, a unit operation in the ConsiGmaTM-25 continuous powder-to-tablet system (GEA Pharma systems, Collette, Wommelgem, Belgium), the product under study presents itself as a collection of particles that differ in shape and size. The measurement of this collection results in a particle size distribution. However, the theoretical basis to describe the physical phenomena leading to changes in this particle size distribution is lacking. It is essential to understand how the particle size distribution changes as a function of the unit operation's process settings, as it has a profound effect on the behavior of the fluid bed dryer. Therefore, we suggest a data-driven modeling framework that links the machine settings of the wet granulation unit operation and the output distribution of granules. We do this without making any assumptions on the nature of the distributions under study. A simulation of the granule size distribution could act as a soft sensor when in-line measurements are challenging to perform. The method of this work is a two-step procedure: first, the measured distributions are transformed into a high-dimensional feature space, where the relation between the machine settings and the distributions can be learnt. Second, the inverse transformation is performed, allowing an interpretation of the results in the original measurement space. Further, a comparison is made with previous work, which employs a more mechanistic framework for describing the granules. A reliable prediction of the granule size is vital in the assurance of quality in the production line, and is needed in the assessment of upstream (feeding) and downstream (drying, milling, and tableting) issues. Now that a validated data-driven framework for predicting pharmaceutical particle size distributions is available, it can be applied in settings such as model-based experimental design and, due to its fast computation, there is potential in real-time model predictive control

The Measure and Mismeasure of Fairness: A Critical Review of Fair Machine Learning

The nascent field of fair machine learning aims to ensure that decisions guided by algorithms are equitable. Over the last several years, three formal definitions of fairness have gained prominence: (1) anti-classification, meaning that protected attributes---like race, gender, and their proxies---are not explicitly used to make decisions; (2) classification parity, meaning that common measures of predictive performance (e.g., false positive and false negative rates) are equal across groups defined by the protected attributes; and (3) calibration, meaning that conditional on risk estimates, outcomes are independent of protected attributes. Here we show that all three of these fairness definitions suffer from significant statistical limitations. Requiring anti-classification or classification parity can, perversely, harm the very groups they were designed to protect; and calibration, though generally desirable, provides little guarantee that decisions are equitable. In contrast to these formal fairness criteria, we argue that it is often preferable to treat similarly risky people similarly, based on the most statistically accurate estimates of risk that one can produce. Such a strategy, while not universally applicable, often aligns well with policy objectives; notably, this strategy will typically violate both anti-classification and classification parity. In practice, it requires significant effort to construct suitable risk estimates. One must carefully define and measure the targets of prediction to avoid retrenching biases in the data. But, importantly, one cannot generally address these difficulties by requiring that algorithms satisfy popular mathematical formalizations of fairness. By highlighting these challenges in the foundation of fair machine learning, we hope to help researchers and practitioners productively advance the area

Discriminative conditional restricted Boltzmann machine for discrete choice and latent variable modelling

Conventional methods of estimating latent behaviour generally use attitudinal questions which are subjective and these survey questions may not always be available. We hypothesize that an alternative approach can be used for latent variable estimation through an undirected graphical models. For instance, non-parametric artificial neural networks. In this study, we explore the use of generative non-parametric modelling methods to estimate latent variables from prior choice distribution without the conventional use of measurement indicators. A restricted Boltzmann machine is used to represent latent behaviour factors by analyzing the relationship information between the observed choices and explanatory variables. The algorithm is adapted for latent behaviour analysis in discrete choice scenario and we use a graphical approach to evaluate and understand the semantic meaning from estimated parameter vector values. We illustrate our methodology on a financial instrument choice dataset and perform statistical analysis on parameter sensitivity and stability. Our findings show that through non-parametric statistical tests, we can extract useful latent information on the behaviour of latent constructs through machine learning methods and present strong and significant influence on the choice process. Furthermore, our modelling framework shows robustness in input variability through sampling and validation

Distinguishing cause from effect using observational data: methods and benchmarks

The discovery of causal relationships from purely observational data is a fundamental problem in science. The most elementary form of such a causal discovery problem is to decide whether X causes Y or, alternatively, Y causes X, given joint observations of two variables X, Y. An example is to decide whether altitude causes temperature, or vice versa, given only joint measurements of both variables. Even under the simplifying assumptions of no confounding, no feedback loops, and no selection bias, such bivariate causal discovery problems are challenging. Nevertheless, several approaches for addressing those problems have been proposed in recent years. We review two families of such methods: Additive Noise Methods (ANM) and Information Geometric Causal Inference (IGCI). We present the benchmark CauseEffectPairs that consists of data for 100 different cause-effect pairs selected from 37 datasets from various domains (e.g., meteorology, biology, medicine, engineering, economy, etc.) and motivate our decisions regarding the "ground truth" causal directions of all pairs. We evaluate the performance of several bivariate causal discovery methods on these real-world benchmark data and in addition on artificially simulated data. Our empirical results on real-world data indicate that certain methods are indeed able to distinguish cause from effect using only purely observational data, although more benchmark data would be needed to obtain statistically significant conclusions. One of the best performing methods overall is the additive-noise method originally proposed by Hoyer et al. (2009), which obtains an accuracy of 63+-10 % and an AUC of 0.74+-0.05 on the real-world benchmark. As the main theoretical contribution of this work we prove the consistency of that method.Comment: 101 pages, second revision submitted to Journal of Machine Learning Researc

Psychometrics in Practice at RCEC

A broad range of topics is dealt with in this volume: from combining the psychometric generalizability and item response theories to the ideas for an integrated formative use of data-driven decision making, assessment for learning and diagnostic testing. A number of chapters pay attention to computerized (adaptive) and classification testing. Other chapters treat the quality of testing in a general sense, but for topics like maintaining standards or the testing of writing ability, the quality of testing is dealt with more specifically.\ud All authors are connected to RCEC as researchers. They present one of their current research topics and provide some insight into the focus of RCEC. The selection of the topics and the editing intends that the book should be of special interest to educational researchers, psychometricians and practitioners in educational assessment