Preterm Birth Prediction: Deriving Stable and Interpretable Rules from High Dimensional Data

Preterm births occur at an alarming rate of 10-15%. Preemies have a higher risk of infant mortality, developmental retardation and long-term disabilities. Predicting preterm birth is difficult, even for the most experienced clinicians. The most well-designed clinical study thus far reaches a modest sensitivity of 18.2-24.2% at specificity of 28.6-33.3%. We take a different approach by exploiting databases of normal hospital operations. We aims are twofold: (i) to derive an easy-to-use, interpretable prediction rule with quantified uncertainties, and (ii) to construct accurate classifiers for preterm birth prediction. Our approach is to automatically generate and select from hundreds (if not thousands) of possible predictors using stability-aware techniques. Derived from a large database of 15,814 women, our simplified prediction rule with only 10 items has sensitivity of 62.3% at specificity of 81.5%.Comment: Presented at 2016 Machine Learning and Healthcare Conference (MLHC 2016), Los Angeles, C

Optimal Transient Real-Time Engine-Generator Control in the Series-Hybrid Vehicle

We study the dynamic engine-generator optimal control problem with a goal of minimizing fuel consumption while delivering a requested average electrical power. By using an infinite-horizon formulation and explicitly minimizing fuel consumption, we avoid issues inherent with penalty-based and finite-horizon problems. The solution to the optimal control problem, found using dynamic programming and the successive approximation method, can be expressed as instantaneous non-linear state-feedback. This allows for trivial real-time control, typically requiring 10–20 CPU instructions per control period, a few bytes of RAM, and 5–20 KiB of nonvolatile memory. Simulation results for a passenger vehicle indicate a fuel consumption improvement in the region of 5–7% during the transient phase when compared with the class of controllers found in the industry. Bench-tests, where the optimal controller is executed in native hardware, show an improvement of 3.7%, primarily limited by unmodeled dynamics. Our specific choice of problem formulation, a guaranteed globally optimal solution, and trivial real-time control resolve many of the limitations with the current state of optimal engine-generator controllers

Tunable nanopatterning of conductive polymers via electrohydrodynamic lithography

[Image: see text] An increasing number of technologies require the fabrication of conductive structures on a broad range of scales and over large areas. Here, we introduce advanced yet simple electrohydrodynamic lithography (EHL) for patterning conductive polymers directly on a substrate with high fidelity. We illustrate the generality of this robust, low-cost method by structuring thin polypyrrole films via electric-field-induced instabilities, yielding well-defined conductive structures with feature sizes ranging from tens of micrometers to hundreds of nanometers. Exploitation of a conductive polymer induces free charge suppression of the field in the polymer film, paving the way for accessing scale sizes in the low submicron range. We show the feasibility of the polypyrrole-based structures for field-effect transistor devices. Controlled EHL pattering of conductive polymer structures at the micro and nano scale demonstrated in this study combined with the possibility of effectively tuning the dimensions of the tailor-made architectures might herald a route toward various submicron device applications in supercapacitors, photovoltaics, sensors, and electronic displays

Advanced micro-engineered platforms for novel device technologies

The objectives of this thesis are to explore, design, fabricate and implement the use of advanced micro-engineered platforms to be exploited as versatile, novel device technologies. An increasing number of technologies require the fabrication of conductive structures on a broad range of scales and large areas. Here, we introduce advanced yet simple electrohydrodynamic lithography for patterning conductive polymers directly on a substrate with high-fidelity. We illustrate the generality of this robust, low-cost method by structuring thin films via electric-field-induced instabilities, yielding well-defined conductive structures with a broad range of feature sizes. We show the feasibility of the polypyrrole-based structures for field-effect transistors, which might herald a route towards submicron device applications. We also demonstrate a miniaturised platform technology for timely, sensitive and rapid point-of-care diagnostics of disease-indicative biomarkers. Our micro-engineered device technology (MEDTech) is based on reproducible electrohydrodynamically fabricated platforms for surface enhanced Raman scattering enabling tuneable, high-throughput nanostructures yielding high-signal enhancements. These, integrated within a microfluidic-chip provide cost-effective, portable devices for detection of miniscule biomarker concentrations from biofluids, offering clinical tests that are simple, rapid and minimally invasive. Using MEDTech to analyse clinical blood-plasma, we deliver a prognostic tool for long-term outcomes, in the hospital or at the point-of-care

Treatment of vaginal candidiasis for the prevention of preterm birth: a systematic review and meta-analysis

Abstract Background: Recognition that ascending infection leads to preterm birth has led to a number of studies that have evaluated the treatment of vaginal infections in pregnancy to reduce preterm birth rates. However, the role of candidiasis is relatively unexplored. Our aim was to undertake a systematic review and meta-analysis to assess whether treatment of pregnant women with vulvovaginal candidiasis reduces preterm birth rates and other adverse birth outcomes. Methods: We undertook a systematic review and meta-analysis of randomised controlled trials (RCTs) in which pregnant women were treated for vulvovaginal candidias (compared to placebo or no treatment) and where preterm birth was reported as an outcome. Trials were identified by searching the Cochrane Central Register of Controlled Trials, Medline and Embase databases to January 2014. Trial eligibility and outcomes were pre-specified. Two reviewers independently assessed the studies against the agreed criteria and extracted relevant data using a standard data extraction form. Meta-analysis was used to calculate pooled rate ratios (RR) and 95% confidence intervals (CI) using a fixed-effects model. Results: There were 2 eligible RCTs both among women with asymptomatic candidiasis, with a total of 685 women randomised. Both trials compared treatment with usual care (no screening for, or treatment of, asymptomatic candidiasis). Data from one trial involved a post-hoc analysis of a larger trial of treatment of asymptomatic infections in pregnancy (n=586) and the other was a pilot study (n=99). There was a significant reduction in spontaneous preterm births in treated compared with untreated women (meta-analysis RR=0.36, 95%CI 0.17-0.75). No other outcomes were assessed by both trials. Conclusions: This systematic review found two trials comparing treatment of vaginal candidiasis in pregnancy for the outcome of preterm birth. Although the effect estimate provides support for the hypothesis that treatment of asymptomatic candidiasis may reduce 3 the risk of preterm birth, the result needs to be interpreted with caution as the primary driver for the pooled estimate comes from a post-hoc analysis. A prospective trial with sufficient power to answer the clinical question ‘does treatment of asymptomatic candidiasis in early pregnancy prevent preterm birth’ is warranted.Australian National Health and Medical Research Council (NHMRC) Project Grant (#632544). CLR is supported by a NHMRC Senior Research Fellowship (#APP1021025)

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro-Hydrodynamic Surface Molecular Lithography

Micro- and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab-on-a-chip diagnostics. Herein, a micro- and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro-hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro- and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high-precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro- and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano-plasmonic lab-on-a-chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point-of-care detection of disease-indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost-effective micro- and nanoplatforms for accurate detection.</p

Window into the mind:Advanced handheld spectroscopic eye-safe technology for point-of-care neurodiagnostic

Traumatic brain injury (TBI), a major cause of morbidity and mortality worldwide, is hard to diagnose at the point of care with patients often exhibiting no clinical symptoms. There is an urgent need for rapid point-of-care diagnostics to enable timely intervention. We have developed a technology for rapid acquisition of molecular fingerprints of TBI biochemistry to safely measure proxies for cerebral injury through the eye, providing a path toward noninvasive point-of-care neurodiagnostics using simultaneous Raman spectroscopy and fundus imaging of the neuroretina. Detection of endogenous neuromarkers in porcine eyes' posterior revealed enhancement of high-wave number bands, clearly distinguishing TBI and healthy cohorts, classified via artificial neural network algorithm for automated data interpretation. Clinically, translating into reduced specialist support, this markedly improves the speed of diagnosis. Designed as a hand-held cost-effective technology, it can allow clinicians to rapidly assess TBI at the point of care and identify long-term changes in brain biochemistry in acute or chronic neurodiseases.</p

Systematic review and meta‐analysis of the effects of foot and ankle physical therapy, including mobilisations and exercises, in people with diabetic peripheral neuropathy on range of motion, peak plantar pressures and balance

To evaluate the effects of foot and ankle physical therapy on ankle and first metatarsophalangeal joint range of motion (ROM), peak plantar pressures (PPPs) and balance in people with diabetes. MEDLINE, EBSCO, Cochrane Database of Systematic Reviews, Joanna Briggs Institute Database of Systematic Reviews, PROSPERO, EThOS, Web of Science and Google Scholar were searched in April 2022. Randomised Controlled Trials (RCT), quasi-experimental, pre-post experimental design and prospective cohort studies were included. Participants were people with diabetes, neuropathy and joint stiffness. Interventions included physical therapy such as mobilisations, ROM exercises and stretches. Outcome measures focused on ROM, PPPs and balance. Methodological quality was assessed with Critical Appraisal Skills Programme RCT and Risk-of-Bias 2 tool. Meta-analyses used random-effects models and data was analysed using the inverse variance method. In total, 9 studies were included. Across all studies, participant characteristics were similar; however, type and exercise dosage varied greatly. Meta-analysis was performed with four studies. Meta-analysis showed significant effects of combined exercise interventions in increasing total ankle ROM (3 studies: MD, 1.76; 95% CI, 0.78–2.74; p = 0; I2 = 0%); and reducing PPPs in the forefoot area (3 studies; MD, −23.34; 95% CI, −59.80 to 13.13; p = 0.21, I2 = 51%). Combined exercise interventions can increase ROM in the ankle and reduce PPPs in the forefoot. Standardisation of exercise programmes with or without the addition of mobilisations in the foot and ankle joints needs further research

Spectroscopic profiling variations in extracellular vesicle biochemistry in a model of myogenesis.

Extracellular vesicles (EVs) hold value as accessible biomarkers for understanding cellular differentiation and related pathologies. Herein, EV biomarkers in models of skeletal muscle dormancy and differentiation have been comparatively profiled using Raman spectroscopy (RS). Significant variations in the biochemical fingerprint of EVs were detected, with an elevation in peaks associated with lipid and protein signatures during early myogenic differentiation (day 2). Principal component analysis revealed a clear separation between the spectra of EVs derived from myogenic and senescent cell types, with non-overlapping interquartile ranges and population median. Observations aligned with nanoparticle tracking data, highlighting a significant early reduction in EV concentration in senescent myoblast cultures as well as notable variations in EV morphology and diameter. As differentiation progressed physical and biochemical differences in the properties of EVs became less pronounced. This study demonstrates the applicability of RS as a high-resolution analytical method for profiling biochemical changes in EVs during early myogenesis