Development and Validation of UPLC-MS/MS Method for Rapid Simultaneous Determination of Levothyroxine and Liothyronine in Human Serum

A simple ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed and fully validated to simultaneously determine levothyroxine (LT4) and liothyronine (LT3) in human serum. Sample preparation was done through protein precipitation with acetonitrile. HyPURITY C18 column was selected to achieve rapid separation for LT4 and LT3 within 4 min. Electrospray ionization (ESI) under multiple reaction monitoring (MRM) was used to monitor the ion transitions for LT4 (m/z 777.54→731.52), LT3 (m/z 651.64→ 605.65) and internal standard LT4-D3 (m/z 780.53 →734.19), operating in the positive ion mode. The method was proved to be accurate (82.35% to 113.56%) and precise (0.73% to 8.28%) over concentration range of 50.37 ng/ml – 300.13 ng/ml for LT4 and 0.5 ng/ml – 50.37 ng/ml for LT3. The validated method could be applied for pharmacokinetic study or bioequivalence testing of combination products of LT4 and LT3. Keywords: Levothyroxine; Liothyronine; Ultra Performance Liquid Chromatographic; Mass Spectrometry; Human Seru

Generating Medical Prescriptions with Conditional Transformer

Access to real-world medication prescriptions is essential for medical research and healthcare quality improvement. However, access to real medication prescriptions is often limited due to the sensitive nature of the information expressed. Additionally, manually labelling these instructions for training and fine-tuning Natural Language Processing (NLP) models can be tedious and expensive. We introduce a novel task-specific model architecture, Label-To-Text-Transformer (\textbf{LT3}), tailored to generate synthetic medication prescriptions based on provided labels, such as a vocabulary list of medications and their attributes. LT3 is trained on a set of around 2K lines of medication prescriptions extracted from the MIMIC-III database, allowing the model to produce valuable synthetic medication prescriptions. We evaluate LT3's performance by contrasting it with a state-of-the-art Pre-trained Language Model (PLM), T5, analysing the quality and diversity of generated texts. We deploy the generated synthetic data to train the SpacyNER model for the Named Entity Recognition (NER) task over the n2c2-2018 dataset. The experiments show that the model trained on synthetic data can achieve a 96-98\% F1 score at Label Recognition on Drug, Frequency, Route, Strength, and Form. LT3 codes and data will be shared at \url{https://github.com/HECTA-UoM/Label-To-Text-Transformer}Comment: Accepted to: Workshop on Synthetic Data Generation with Generative AI (SyntheticData4ML Workshop) at NeurIPS 202

Optimal Fertility Decisions in a Life Cycle Model

This model is the first to solve for the optimal timing of childbirth and number of children in a continuous time framework simultaneously. The model depicts how changes in wage at different stages of an individual’s life influence the timing decision of childbirth and the optimal number of children. When a woman wants to have more children, she decides to have them at a younger age. Medical research that extends the fecund life span induces women to have fewer children. A reduction of the parental leave due to daycare centers or a reduction in the costs of leave due to child benefits increase the number of children. Women value labour more, when they face the risk of an unknown divorce. This paper also shows that divorce does not change the timing of childbirth directly, it influences the number of children negatively and the reduced number of children delays the timing. The model can be used to predict upper bound fertility rates, when the expected divorce rate continues to increase

Use of thyroid hormones in hypothyroid and euthyroid patients: A survey of members of the Endocrine Society of Australia

\ua9 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.Objective: Hypothyroidism is a common endocrine condition usually managed with levothyroxine (LT4). However, controversy remains around the use of liothyronine (LT3). We aimed to investigate the practices of Australian endocrinologists when managing patients with hypothyroidism, their use of LT3 + LT4 combination therapy and use of thyroid hormones in euthyroid patients. Design and Participants: Members of the Endocrine Society of Australia (ESA) were invited to participate in an online questionnaire. Measurements: We analysed questionnaires that had complete demographic data. Results: Eighty-seven questionnaires fulfilled the criteria. LT4 was used as first line treatment for hypothyroidism by all respondents. Only 45% reported that their patients were dispensed the brand of LT4 that they recommend. LT3 (alone or in combination) was prescribed by 44% in their clinical practice. Although 49% of respondents would consider LT3 + LT4 in patients with normal TSH who had ongoing symptoms of hypothyroidism, the inability of LT4 to restore normal physiology was ranked the least likely explanation for persistent symptoms and only 32% would consider it for themselves if they were diagnosed with hypothyroidism. The majority (55%), in accordance with evidence, would not prescribe thyroid hormone to euthyroid individuals but 39% would consider use in euthyroid female infertility with high levels of thyroid antibodies and 11% in euthyroid patients with a simple goitre growing over time. LT4 use in pregnancy was variable among members. Conclusions: Australian endocrinologists mostly follow international guidelines when prescribing thyroid hormone therapy and many prescribe combination LT3 and LT4 therapy, particularly for patients who remain symptomatic on LT4 monotherapy. Prescribing practices are largely similar to other countries who have completed similar questionnaires

Measuring complexity in a business cycle

The purpose of this paper is to study the dynamical behavior of a family of two- dimensional nonlinear maps associated to an economic model. Our objective is to measure the complexity of the system using techniques of symbolic dynamics in order to compute the topological entropy. The analysis of the variation of this im- portant topological invariant with the parameters of the system, allows us to distin- guish different chaotic scenarios. Finally, we use a another topological invariant to distinguish isentropic dynamics and we exhibit numerical results about maps with the same topological entropy. This work provides an illustration of how our under- standing of higher dimensional economic models can be enhanced by the theory of dynamical systems

Monopole solutions to the Bogomolny equation as three-dimensional generalizations of the Kronecker series

The Dirac monopole on a three-dimensional torus is considered as a solution to the Bogomolny equation with non-trivial boundary conditions. The analytical continuation of the obtained solution is shown to be a three-dimensional generalization of the Kronecker series. It satisfies the corresponding functional equation and is invariant under modular transformations.Comment: 13 pages, 1 figur

The GW/LT3 VarDial 2016 shared task system for dialects and similar languages detection

This paper describes the GW/LT3 contribution to the 2016 VarDial shared task on the identification of similar languages (task 1) and Arabic dialects (task 2). For both tasks, we experimented with Logistic Regression and Neural Network classifiers in isolation. Additionally, we implemented a cascaded classifier that consists of coarse and fine-grained classifiers (task 1) and a classifier ensemble with majority voting for task 2. The submitted systems obtained state-of-the-art performance and ranked first for the evaluation on social media data (test sets B1 and B2 for task 1), with a maximum weighted F1 score of 91.94%

Stellar Bar Evolution in Cuspy and Flat-Cored Triaxial CDM Halos

We analyze the evolution of stellar bars in galactic disks in mildly triaxial flat-core and cuspy CDM halos. We use tailored simulations of rigid and live halos which include the feedback from disk/bar onto the halo in order to test the work by El-Zant & Shlosman (2002). The latter used the Liapunov exponents to analyze the fate of bars in analytical asymmetric halos. We find: (1) The bar growth is similar in all rigid axisymmetric and triaxial halos. (2) Bars in live models vertically buckle and form a pseudobulge with a boxy/peanut shape. (3) In live axisymmetric halos, the bar strength varies little during the secular evolution. The bar pattern speed anticorrelates with the halo core size. The bar strength is larger for smaller disk-to-halo mass ratios within disk radii, the bar size correlates with the halo core sizes, and the bar pattern speeds -- with the halo central mass concentration. Bars embedded in live triaxial halos have a starkly different fate: they dissolve on ~1.5-5 Gyr due to the onset of chaos over continuous zones, leaving behind a weak oval distortion. The onset of chaos is related to the halo triaxiality, the fast rotating bar and the halo cuspiness. Before the bar dissolves, the region outside it develops strong spiral structures, especially in the live triaxial halos. (4) More angular momentum is absorbed by the triaxial halos as compared to the axisymmetric models and its exchange is mediated by resonances. (5) Cuspy halos are more susceptible than flat-core halos to having their prolateness washed out by the bar. We analyze these results in terms of the stability of trajectories and development of chaos. We set constraints on the triaxiality of DM halos by comparing our predictions to recent observations of bars out to z~1.Comment: 17 pages, 14 figures, Astrophysical Journal, in press, Vol. 637. Updated version (text, references