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Large Language Model (LLM) fine tuning is underutilized in the field of medicine. Two of the most common methods of fine tuning are Supervised Fine Tuning (SFT) and Direct Preference Optimization (DPO), but there is little guidance informing users when to use either technique. In this investigation, we compare the performance of SFT and DPO for five common natural language tasks in medicine: Classification with text data, Classification with numeric data, Clinical Reasoning, Summarization, and Clinical Triage. We find that SFT alone is sufficient for Classification with text data, whereas DPO improves performance for the more complex tasks of Clinical Reasoning, Summarization and Clinical Triage. Our results establish the role and importance of DPO fine tuning within medicine, and consequently call attention to current software gaps that prevent widespread deployment of this technique.

Background: This study aimed to evaluate and compare the performance of classical machine learning models (CMLs) and large language models (LLMs) in predicting mortality associated with COVID-19 by utilizing a high-dimensional tabular dataset. Materials and Methods: We analyzed data from 9,134 COVID-19 patients collected across four hospitals. Seven CML models, including XGBoost and random forest (RF), were trained and evaluated. The structured data was converted into text for zero-shot classification by eight LLMs, including GPT-4 and Mistral-7b. Additionally, Mistral-7b was fine-tuned using the QLoRA approach to enhance its predictive capabilities. Results: Among the CML models, XGBoost and RF achieved the highest accuracy, with F1 scores of 0.87 for internal validation and 0.83 for external validation. In the LLM category, GPT-4 was the top performer with an F1 score of 0.43. Fine-tuning Mistral-7b significantly improved its recall from 1% to 79%, resulting in an F1 score of 0.74, which was stable during external validation. Conclusion: While LLMs show moderate performance in zero-shot classification, fine-tuning can significantly enhance their effectiveness, potentially aligning them closer to CML models. However, CMLs still outperform LLMs in high-dimensional tabular data tasks., Comment: Code is available at: https://github.com/mohammad-gh009/Large-Language-Models-vs-Classical-Machine-learning and https://github.com/Sdamirsa/Tehran_COVID_Cohort. The datasets are available from the corresponding author on reasonable request (sdamirsa@ymail.com)

Background and Aims: This study evaluates the medical reasoning performance of large language models (LLMs) and vision language models (VLMs) in gastroenterology. Methods: We used 300 gastroenterology board exam-style multiple-choice questions, 138 of which contain images to systematically assess the impact of model configurations and parameters and prompt engineering strategies utilizing GPT-3.5. Next, we assessed the performance of proprietary and open-source LLMs (versions), including GPT (3.5, 4, 4o, 4omini), Claude (3, 3.5), Gemini (1.0), Mistral, Llama (2, 3, 3.1), Mixtral, and Phi (3), across different interfaces (web and API), computing environments (cloud and local), and model precisions (with and without quantization). Finally, we assessed accuracy using a semiautomated pipeline. Results: Among the proprietary models, GPT-4o (73.7%) and Claude3.5-Sonnet (74.0%) achieved the highest accuracy, outperforming the top open-source models: Llama3.1-405b (64%), Llama3.1-70b (58.3%), and Mixtral-8x7b (54.3%). Among the quantized open-source models, the 6-bit quantized Phi3-14b (48.7%) performed best. The scores of the quantized models were comparable to those of the full-precision models Llama2-7b, Llama2--13b, and Gemma2-9b. Notably, VLM performance on image-containing questions did not improve when the images were provided and worsened when LLM-generated captions were provided. In contrast, a 10% increase in accuracy was observed when images were accompanied by human-crafted image descriptions. Conclusion: In conclusion, while LLMs exhibit robust zero-shot performance in medical reasoning, the integration of visual data remains a challenge for VLMs. Effective deployment involves carefully determining optimal model configurations, encouraging users to consider either the high performance of proprietary models or the flexible adaptability of open-source models., Comment: Manuscript Pages: 34, Figures: 7, Tables: 2, Supplementary File Pages: 35, Data Transparency Statement: Code is available at: https://github.com/Sdamirsa/LLM-VLM-in-Gastroenterology . Study data from American College of Gastroenterology (ACG) are restricted and available upon request with ACG permission. Correction: updated abstract considering Llama3.1 results

Large Language Models have difficulty communicating uncertainty, which is a significant obstacle to applying LLMs to complex medical tasks. This study evaluates methods to measure LLM confidence when suggesting a diagnosis for challenging clinical vignettes. GPT4 was asked a series of challenging case questions using Chain of Thought and Self Consistency prompting. Multiple methods were investigated to assess model confidence and evaluated on their ability to predict the models observed accuracy. The methods evaluated were Intrinsic Confidence, SC Agreement Frequency and CoT Response Length. SC Agreement Frequency correlated with observed accuracy, yielding a higher Area under the Receiver Operating Characteristic Curve compared to Intrinsic Confidence and CoT Length analysis. SC agreement is the most useful proxy for model confidence, especially for medical diagnosis. Model Intrinsic Confidence and CoT Response Length exhibit a weaker ability to differentiate between correct and incorrect answers, preventing them from being reliable and interpretable markers for model confidence. We conclude GPT4 has a limited ability to assess its own diagnostic accuracy. SC Agreement Frequency is the most useful method to measure GPT4 confidence.

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and an 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. We make MedAlign available under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.

One of the major barriers to using large language models (LLMs) in medicine is the perception they use uninterpretable methods to make clinical decisions that are inherently different from the cognitive processes of clinicians. In this manuscript we develop novel diagnostic reasoning prompts to study whether LLMs can perform clinical reasoning to accurately form a diagnosis. We find that GPT4 can be prompted to mimic the common clinical reasoning processes of clinicians without sacrificing diagnostic accuracy. This is significant because an LLM that can use clinical reasoning to provide an interpretable rationale offers physicians a means to evaluate whether LLMs can be trusted for patient care. Novel prompting methods have the potential to expose the black box of LLMs, bringing them one step closer to safe and effective use in medicine.

Processes involving the manufacture of fine/bulk chemicals, pharmaceuticals, biofuels, and waste treatment require plug flow characteristics to minimise their energy consumption and costs, and maximise product quality. One such versatile flow chemistry platform is the coiled tube reactor subjected to oscillatory motion, producing excellent plug flow qualities equivalent to well-mixed tanks-in-series 'N'. In this study, we discover the critical features of these flows that result in high plug flow performance using a data-driven approach. This is done by integrating Bayesian optimisation, a surrogate model approach, with Computational fluid dynamics that we treat as a black-box function to explore the parameter space of the operating conditions, oscillation amplitude and frequency, and net flow rate. Here, we correlate the flow characteristics as a function of the dimensionless Strouhal, oscillatory Dean, and Reynolds numbers to the reactor plug flow performance value 'N'. Under conditions of optimal performance (specific examples are provided herein), the oscillatory flow is just sufficient to limit axial dispersion through flow reversal and redirection, and to promote Dean vortices. This automated, open-source, integrated method can be easily adapted to identify the flow characteristics that produce an optimised performance for other chemical reactors and processes.

We prove the Hot Spot conjecture on the Vicsek set. Specifically, we show that every eigenfunction of the second smallest eigenvalue of the Neumann Laplacian on the Vicsek set attains its maximum and minimum on the boundary., Comment: We made changes suggested by the anonymous referee and editors. The paper is accepted for publication in the Special Issue on Harmonic Analysis: Smooth and Non-Smooth, Demonstratio Mathematica