Predicting hypotensive episodes in the traumatic brain injury domain

The domain with which this research is concerned is traumatic brain injury and models which attempt to predict hypotensive (low blood pressure) events occurring in a hospital intensive care unit environment. The models process anonymised, clinical, minute-byminute, physiological data from the BrainIT consortium. The research reviews three predictive modelling techniques: classic time series analysis; hidden Markov models; and classifier models, which are the main focus of this thesis. The data preparation part of this project is extensive and six applications have been developed: an event list generator, used to process a given event definition; a data set generation tool, which produces a series of base data sets that can be used to train machine learning models; a training and test set generation application, which produces randomly drawn training and test data sets; an application used to build and assess a series of logistic regression models; an application to test the statistical models on unseen data, which uses anonymised real clinical data from intensive care unit bedside monitors; and finally, an application that implements a proposed clinical warning protocol, which attempts to assess a model’s performance in terms of usefulness to a clinical team. These applications are being made available under a public domain licence to enable further research (see Appendix A for details). Six logistic regression models and two Bayesian neural network models are examined using the physiological signals heart rate and arterial blood pressure, along with the demographic variables of age and gender. Model performance is assessed using the standard ROC technique to give the AUC metric. An alternative performance metric, the H score, is also investigated. Using unseen clinical data, two of the models are assessed in a manner which mimics the ICU environment. This approach shows that models may perform better than would be suggested by standard assessment metrics. The results of the modelling experiments are compared with a recent similar project in the healthcare domain and show that logistic regression models could form the basis of a practical early warning system for use in a neuro intensive care unit

SEM/STEM observations of magnetite in carbonates of eastern North America: Evidence for chemical remagnettzation during the Alleghenian Orogeny

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95085/1/grl5458.pd

Modified lattice parameter/Curie temperature diagrams for Titanomagnetite/titanomaghemite within the quadrilateral Fe 3 O 4 ‐ Fe 2 TiO 4 ‐Fe 2 O 3 ‐Fe 2 TiO 5

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94971/1/grl9245.pd

The Effects of Methylphenidate on Cognitive Control in Active Methamphetamine Dependence Using Functional Magnetic Resonance Imaging

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18–46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects

Engineering Controls for Bioaerosols in Non-Industrial/Non-Healthcare Settings

The list of disease pathogens that can be transmitted in the air is extensive. This list includes the common cold, SARS, measles, Hansen’s disease (leprosy), polio, influenza, Legionella (Legionnaires’ disease and Pontiac fever), and tuberculosis (TB). TB, SARS-CoV-1, avian influenza, varicella, and now SARS-CoV-2 all have received public notice due not only to their known or assumed ability to be transmitted in the air rapidly from one individual to another, but also for their virulence. Other bioaerosols that can be transmitted through the air include bacteria, fungal spores and fragments, dust mites, and pollen. This document was developed to address control of bioaerosols transmission, primarily through ventilation and other engineering controls. This monograph will focus on engineering controls in non-industrial/ non-healthcare facilities such as office buildings, schools, public assembly, theaters, and governmental buildings. It does not, however, address ventilation in residences, either single or multi-family

Effect of Preventive Supplementation with Zinc and other Micronutrients on Non-Malarial Morbidity in Tanzanian Pre-School Children: A Randomized Trial.

The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity. Rural Tanzanian children (n = 612) aged 6-60 months and with height-for-age z-score < -1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%-40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94-1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24-3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57-0.96), but we found no evidence that it reduced the overall number of clinic visits. We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics. ClinicalTrials.gov NCT00623857

SEM/STEM observation of magnetic minerals in presumably unremagnetized Paleozoic carbonates from Indiana and Alabama

The Silurian Wabash Formation in Indiana and the Mississippian Pride Mountain Formation in Alabama appear not to have been affected by a late Paleozoic remagnetization event. In an attempt to characterize the magnetic mineralogy in these (presumably) unremagnetized carbonates and in order to compare their magnetic mineralogy to that of remagnetized carbonates, scanning and scanning transmission microscope (SEM/STEM) observations and rock magnetic investigations were carried out.It is possible to recognize differences in magnetic mineralogy in the unremagnetized carbonate from that in remagnetized carbonates: 1. (1) iron oxides associated with iron sulfides are hematite (in this study) as a result of replacement of pyrite (instead of magnetite as was found elsewhere);2. (2) occurrences of large euhedral pure-iron oxides of secondary origin are common in the unremagnetized carbonates3. (3) a rare occurrence of fine-grained single-crystal magnetite capable of carrying a remanence in the unremagnetized carbonates is noticeable as compared to the abundance of such grains in the remagnetized carbonates. Although the abundance of the fine-grained magnetite grains in remagnetized carbonates is inferred to be a diagnostic factor to distinguish the remagnetized from the unremagnetized carbonates, this clarifies only the carriers in the remagnetized rocks and leaves the question of the carriers in unremagnetized limestones unresolved to a large extent.The lack of remagnetization is commonly attributed to a restricted amount of fluid influx into the rocks. For the Wabash and the Pride Mountain Formations this may also be true; early cementation has significantly reduced the porosity and permeability in the Wabash Formation in Indiana, whereas the presence of the impermeable Chattanooga Shale may have `protected' the Mississippian Pride Mountain Formation in Alabama.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29677/1/0000004.pd

Reduced expression of PML predisposes to Paget's disease of bone by increasing osteoclast differentiation and bone resorption

Paget's disease of bone (PDB) is characterized by focal increases in bone remodelling. Genome-wide association studies identified a susceptibility locus for PDB tagged by rs5742915, which is located within the PML gene. Here, we have assessed the candidacy of PML as the predisposing gene for PDB at this locus. We found that the PDB-risk allele of rs5742915 was associated with lower PML expression and that PML expression in blood cells from individuals with PDB was lower than in controls. The differentiation, survival and resorptive activity of osteoclasts prepared from Pml-/- mice was increased compared with wild type. Furthermore, the inhibitory effect of IFN-γ on osteoclast formation from Pml-/- was significantly blunted compared with wild type. Bone nodule formation was also increased in osteoblasts from Pml-/- mice when compared with wild type. Although microCT analysis of trabecular bone showed no differences between Pml-/- mice and wild type, bone histomorphometry showed that Pml-/- mice had high bone turnover with increased indices of bone resorption and increased mineral apposition rate. These data indicate that reduced expression of PML predisposes an individual to PDB and identify PML as a novel regulator of bone metabolism. This article has an associated First Person interview with the first author of the paper