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Gilchrist, A.

Publications and source records attributed to Gilchrist, A..

3 recordsLinked to original sources

Recurrent Neural Network-based Acute Concussion Classifier using Raw Resting State EEG Data

Concussion is a global health concern. Despite its high prevalence, a sound understanding of the mechanisms underlying this type of diffuse brain injury remains elusive. It is, however, well established that concussions cause significant functional deficits; that children and youths are disproportionately affected and have longer recovery time than adults; and recovering individuals are more prone to suffer additional concussions, with each successive injury increasing the risk of long term neurological and mental health complications. Currently, concussion management faces two significant challenges: there are no objective, clinically accepted, brain-based approaches for determining (i) whether an athlete has suffered a concussion, and (ii) when the athlete has recovered. Diagnosis is based on clinical testing and self-reporting of symptoms and their severity. Self-reporting is highly subjective and symptoms only indirectly reflect the underlying brain injury. Here, we introduce a deep learning Long Short Term Memory (LSTM)-based recurrent neural network that is able to distinguish between healthy and acute post-concussed adolescent athletes using only a short (i.e. 90 seconds long) sample of resting state EEG data as input. The athletes were neither required to perform a specific task nor subjected to a stimulus during data collection, and the acquired EEG data was neither filtered, cleaned of artefacts, nor subjected to explicit feature extraction. The LSTM network was trained and tested on data from 27 male, adolescent athletes with sports related concussion, bench marked against 35 healthy, adolescent athletes. During rigorous testing, the classifier consistently identified concussions with an accuracy of >90% and its ensemble-median Area Under the Curve (AUC) corresponds to 0.971. This is the first instance of a high-performing classifier that relies only on easy-to-acquire resting state EEG data. It represents a key step towards the development of an easy-to-use, brain-based, automatic classification of concussion at an individual level.

neuroscience↗

Evaluation of Dose Fractionated Polymyxin B on Acute Kidney Injury: A Translational In Vitro Model

The polymyxins are last-line defense for highly resistant infections. Nephrotoxicity, however, is a dose-limiting factor. Yet, approaches to mitigate nephrotoxicity are poorly defined. This study aimed to investigate the impact of dose fractionated (once, twice and thrice daily) polymyxin B (PB) on acute kidney injury (AKI) in a pre-clinical model. Secondarily, we aimed to describe the pharmacokinetic (PK) profile of PB. Sprague-Dawley rats were assigned to experimental groups with different dosing intervals but constant total daily exposure (12 mg/kg/day into single, twice daily, and thrice daily doses) and controls received normal saline subcutaneously over 3 days. Blood and urine samples were collected, and kidneys were harvested at necropsy. A three-compartment model best described the data and Bayesian observed vs. predicted concentration demonstrated bias, imprecision, and R2 of 0.129 mg/L, 0.729 mg2/L2 and 0.652, respectively. PB exposure (i.e. AUC24h) were similar across treatment groups over time (p=0.87). As a representative, urinary KIM-1 were elevated on days 1 and 2 for experimental groups compared to controls, and thrice daily group experienced the most KIM-1 increase [mean increase (95% CI) day 1 from day -1, 4.44 (0.89, 8.00) ng/mL; p=0.018] as compared to control [mean increase (95% CI) day 1 from day -1, 0.03 (-0.42, 0.49) ng/mL; p=0.99]. Correspondingly, significant histopathological damage was observed with the same group (p=0.013) (controls as a referent). Our findings suggested that fractionating the PB dose thrice daily resulted in the most injury in a rat model.

pharmacology and toxicology↗

Urinary biomarker and histopathological evaluation of vancomycin and piperacillin-tazobactam nephrotoxicity in comparison with vancomycin in a rat model and a confirmatory cellular model

IntroductionVancomycin and piperacillin tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic toxicity occurs, only that serum creatinine (SCr) increases with VAN+TZP. The purpose of this study was to assess biologic plausibility by quantifying kidney injury between VAN, TZP, and VAN+TZP treatments using a translational rat model of AKI and rat kidney epithelial cell studies.\n\nMethods(i) Male Sprague-Dawley rats (n=32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1400 mg/kg/day via intraperitoneal injection, or VAN+TZP. Animals were placed in metabolic cages pre-study and on drug dosing days 1-3. Urinary biomarkers and histopathology were analyzed. (ii) Cellular injury of VAN+TZP was assessed in serum-deprived rat kidney cells (NRK-52E) using an alamarBlue(R) viability assay. Cells were incubated with antibiotics VAN, TZP, cefepime, and gentamicin alone or combined with the same drugs plus VAN 1 mg/mL.\n\nResultsIn the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared to controls (P<0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P<0.001 KIM-1, P<0.05 clusterin). Histopathology was only elevated in the VAN group when compared to TZP as a control (P=0.04). Results were consistent across biomarkers and histopathology suggesting that adding TZP did not worsen VAN induced AKI and may even be protective. In NRK-52E cells, VAN alone caused moderate cell death with high doses (IC5048.76 mg/mL). TZP alone did not cause cellular death under the same conditions. VAN+TZP was not different from VAN alone in NRK-52E cells (P>0.2).\n\nConclusionsVAN+TZP does not cause more kidney injury than VAN alone in a rat model of VIKI or in rat kidney epithelial cells.

pharmacology and toxicology↗