Observational causal inference is useful for decisionmaking in medicine when randomized clinical trials (RCTs) are infeasible or nongeneralizable. However, traditional approaches do not always deliver unconfounded causal conclusions in practice. The rise of "doubly robust" nonparametric tools coupled with the growth of deep learning for capturing rich representations of multimodal data offers a unique opportunity to develop and test such models for causal inference on comprehensive electronic health records (EHRs). In this article, we investigate causal modeling of an RCT-established causal association: the effect of classes of antihypertensive on incident cancer risk. We develop a transformer-based model, targeted bidirectional EHR transformer (T-BEHRT) coupled with doubly robust estimation to estimate average risk ratio (RR). We compare our model to benchmark statistical and deep learning models for causal inference in multiple experiments on semi-synthetic derivations of our dataset with various types and intensities of confounding. In order to further test the reliability of our approach, we test our model on situations of limited data. We find that our model provides more accurate estimates of relative risk [least sum absolute error (SAE) from ground truth] compared with benchmark estimations. Finally, our model provides an estimate of class-wise antihypertensive effect on cancer risk that is consistent with results derived from RCTs.

Uninterrupted monitoring of serum lactate levels is a prerequisite in the critical care of patients prone to sepsis, cardiogenic shock, cardiac arrest, or severe lung disease. Yet there exists no device to continuously measure blood lactate in clinical practice. Optical spectroscopy together with multivariate analysis is proposed as a viable noninvasive tool for estimation of lactate in blood. As an initial step towards this goal, we inspected the plausibility of predicting the concentration of sodium lactate (NaLac) from the UV/visible, near-infrared (NIR), and mid-infrared (MIR) spectra of 37 isotonic phosphate-buffered saline (PBS) samples containing NaLac ranging from 0 to 20 mmol/L. UV/visible (300–800 nm) and NIR (800–2600 nm) spectra of PBS samples were collected using the PerkinElmer Lambda 1050 dual-beam spectrophotometer, while MIR (4000–500 cm−1) spectra were collected using the Spectrum two FTIR spectrometer. Absorption bands in the spectra of all three regions were identified and functional groups were assigned. The concentration of lactate in samples was predicted using the Partial Least-Squares (PLS) regression analysis and leave-one-out cross-validation. The regression analysis showed a correlation coefficient (R2) of 0.926, 0.977, and 0.992 for UV/visible, NIR, and MIR spectra, respectively, between the predicted and reference samples. The RMSECV of UV/visible, NIR, and MIR spectra was 1.59, 0.89, and 0.49 mmol/L, respectively. The results indicate that optical spectroscopy together with multivariate models can achieve a superior technique in assessing lactate concentrations.

BACKGROUND: Whether the association between systolic blood pressure (SBP) and risk of cardiovascular disease is monotonic or whether there is a nadir of optimal blood pressure remains controversial. We investigated the association between SBP and cardiovascular events in patients with diabetes across the full spectrum of SBP. METHODS: A cohort of 49 000 individuals with diabetes aged 50 to 90 years between 1990 and 2005 was identified from linked electronic health records in the United Kingdom. Associations between SBP and cardiovascular outcomes (ischemic heart disease, heart failure, stroke, and cardiovascular death) were analyzed using a deep learning approach. RESULTS: Over a median follow-up of 7.3 years, 16 378 cardiovascular events were observed. The relationship between SBP and cardiovascular events followed a monotonic pattern, with the group with the lowest baseline SBP of <120 mm Hg exhibiting the lowest risk of cardiovascular events. In comparison to the reference group with the lowest SBP (<120 mm Hg), the adjusted risk ratio for cardiovascular disease was 1.03 (95% CI, 0.97–1.10) for SBP between 120 and 129 mm Hg, 1.05 (0.99–1.11) for SBP between 130 and 139 mm Hg, 1.08 (1.01–1.15) for SBP between 140 and 149 mm Hg, 1.12 (1.03–1.20) for SBP between 150 and 159 mm Hg, and 1.19 (1.09–1.28) for SBP ≥160 mm Hg. CONCLUSIONS: Using deep learning modeling, we found a monotonic relationship between SBP and risk of cardiovascular outcomes in patients with diabetes, without evidence of a J-shaped relationship.

Fully automated vehicles are expected to have a significant share of the road network traffic in the near future. Several commercial vehicles with full-range Adaptive Cruise Control (ACC) systems or semi-autonomous functionalities are already available on the market. Many research studies aim at leveraging the potential of automated driving in order to improve the fuel efficiency of vehicles. However, in the vast majority of those, fuel efficiency is isolated to the driving dynamics between a single follower-leader pair, hence overlooking the complex nature of traffic. Consequently fuel efficiency and the efficient use of the roadway capacity are framed as conflicting objectives, leading to fuel-economy control models that adopt highly conservative driving styles. This formulation of the problem could be seen as a user-optimal approach, where in spite of delivering savings for individual vehicles, there is the side-effect of the deterioration of traffic flow. An important point that is overlooked is that the inefficient use of roadway capacity gives rise to congested traffic and traffic breakdowns, which in return increases energy costs within the system. The optimisation methods used in these studies entail high computational costs and, therefore, impose a strict constraint on the scope of problem. In this study, the use of car-following models and the limitation of the search space of optimal strategies to the parameter space of these is proposed. The proposed framework enables performing much more comprehensive optimisations and conducting more extensive tests on the collective impacts of fuel-economy driving strategies. The results show that, as conjectured, a "short-sighted" user-optimal approach is unable to deliver overall fuel efficiency. Conversely, a system-optimal formulation for fuel efficient driving is presented, and it is shown that the objectives of fuel efficiency and traffic flow are in fact not only non-conflicting, but also that they could be viewed as one when the global benefits to the network are considered.

Quantification of lactate/lactic acid in critical care environments is essential as lactate serves as an important biochemical marker for the adequacy of the haemodynamic circulation in shock and of cell respiration at the onset of sepsis/septic shock. Hence, in this study, ATR-FTIR was explored as a potential tool for lactate measurement, as the current techniques depend on sample preparation and fails to provide rapid response. Moreover, the effects of pH on PBS samples (7.4, 7, 6.5 and 6) and change in solution conditions (PBS to whole blood) on spectral features were also investigated. A total 189 spectra from five sets of lactate containing media were obtained. Results suggests that lactate could be measured with more than 90% accuracy in the wavenumber range of 1500–600 cm−1. The findings of this study further suggest that there exist no effects of change in pH or media, when estimating lactate concentration changes in this range of the Mid-IR spectral region.

Deep learning has dominated predictive modelling across different fields, but in medicine it has been met with mixed reception. In clinical practice, simple, statistical models and risk scores continue to inform cardiovascular disease risk predictions. This is due in part to the knowledge gap about how deep learning models perform in practice when they are subject to dynamic data shifts; a key criterion that common internal validation procedures do not address. Using linked electronic health records of 1.1 million patients across England aged at least 35 years between 1985 and 2015, we replicated three established statistical models for predicting five-year risk of incident heart failure, stroke, and coronary heart disease. The results were compared with a widely accepted machine learning model (random forests), and a novel deep learning model (BEHRT). In addition to internal validation, we investigated how data shifts affect model discrimination and calibration. To this end, we tested the models on cohorts from (1) distinct geographical regions; (2) different periods. Using internal validation, the deep learning models substantially outperformed the best statistical models by 6%, 8%, and 11% in heart failure, stroke, and coronary heart disease, respectively, in terms of the area under the receiver operating characteristic curve. The performance of all models declined as a result of data shifts; despite this, the deep learning models maintained the best performance in all risk prediction tasks. Updating the model with the latest information can improve discrimination but if the prior distribution changes, the model may remain miscalibrated.

The linear relationship between optical absorbance and the concentration of analytes—as postulated by the Beer-Lambert law—is one of the fundamental assumptions that much of the optical spectroscopy literature is explicitly or implicitly based upon. The common use of linear regression models such as principal component regression and partial least squares exemplifies how the linearity assumption is upheld in practical applications. However, the literature also establishes that deviations from the Beer-Lambert law can be expected when (a) the light source is far from monochromatic, (b) the concentrations of analytes are very high and (c) the medium is highly scattering. The lack of a quantitative understanding of when such nonlinearities can become predominant, along with the mainstream use of nonlinear machine learning models in different fields, have given rise to the use of methods such as random forests, support vector regression, and neural networks in spectroscopic applications. This raises the question that, given the small number of samples and the high number of variables in many spectroscopic datasets, are nonlinear effects significant enough to justify the additional model complexity? In the present study, we empirically investigate this question in relation to lactate, an important biomarker. Particularly, to analyze the effects of scattering matrices, three datasets were generated by varying the concentration of lactate in phosphate buffer solution, human serum, and sheep blood. Additionally, the fourth dataset pertained to invivo, transcutaneous spectra obtained from healthy volunteers in an exercise study. Linear and nonlinear models were fitted to each dataset and measures of model performance were compared to attest the assumption of linearity. To isolate the effects of high concentrations, the phosphate buffer solution dataset was augmented with six samples with very high concentrations of lactate between (100–600 mmol/L). Subsequently, three partly overlapping datasets were extracted with lactate concentrations varying between 0–11, 0–20 and 0–600 mmol/L. Similarly, the performance of linear and nonlinear models were compared in each dataset. This analysis did not provide any evidence of substantial nonlinearities due high concentrations. However, the results suggest that nonlinearities may be present in scattering media, justifying the use of complex, nonlinear models.

Skin hydration is crucial for overall skin health. Maintaining skin hydration levels preserves skin integrity and prevents tissue damage which can lead to several debilitating conditions. Moreover, continuous monitoring of skin hydration can contribute to the diagnosis or management of serious diseases. For instance, sugar imbalance in diabetes mellitus and kidney disease can lead to the loss of bodily fluids and cause dry skin. Therefore, continuous, accurate and non-intrusive monitoring of skin hydration would present a remarkable opportunity for maintaining overall health and wellbeing. There are various techniques to assess skin hydration. Electrical based Corneometers are currently the gold standard in clinical and non-clinical practice. However, these techniques have a number of limitations. In particular, they are costly, sizeable, intrusive, and operator dependent. Recent research has demonstrated that near infrared spectroscopy could be used as a non-intrusive alternative for the measurement of skin water content. The present paper reports the development and in-vitro validation of a noninvasive, portable, skin hydration sensor. The results indicate that the developed sensor can deliver reliable measurements of skin water content.