Does Perioperative Angiotensin-Converting Enzyme Inhibitor Therapy Correlate with Increased use of Vasopressors during Posterior Lumbar Interbody Fusion versus those not Receiving Angiotensin-Converting Enzyme Inhibitor Therapy: A Retrospective Study

Abstract: The purpose of this study was to evaluate if patients who took Angiotensin Converting Enzyme (ACE) inhibitors the morning of surgery for Posterior Lumbar Interbody Fusion (PLIF) required more treatment for intraoperative hypotension. Introduction: PLIF is a surgical procedure used to correct spinal disorders that include compression, instability, pathological lesions, deformities, and pain. PLIF is completed utilizing the prone position for optimal access to the lumbar spine. Complications associated with prone position have included Post-Operative Vision Loss (POVL), compression of abdominal vessels, and head and neck venous compression resulting in neurologic injury. Currently, there are no set recommendations on ACE Inhibitor continuation before surgery, unlike those on a beta antagonist. There is a lack of research on the effect of the continuation of ACE inhibitors on intraoperative hypotension and vasopressor administration. Methodology: This study used a retrospective, case-control study design. A chart review was conducted from January 1, 2007, through January 1, 2017 on patients undergoing PLIF. A total of 200 patients were included in this study sepearted into two groups, those who held their ACE inhibitors and those who continued their ACE inhibitors. Patient information collected included: amount of phenylephrine received, amount of ephedrine received, lowest systolic blood pressure, and lowest diastolic blood pressure. The age and BMI was compared using t-tests and chi-square tests for gender and ASA physical status. A total of two linear regressions were completed to examine the lowest systolic blood pressure, lowest diastolic blood pressure, total phenylephrine dose, and total ephedrine dose. Results: The mean age of the total study sample was 57.25 ± (12.57). There were 47.5% male patients and 52.5% female patients. The mean BMI was 31.01± (6.71). The ASA physical status ranged from 2 to 4 with 27% ASA 2, 69% ASA 3, and 4% ASA 4. There was no statistically significant difference found in age, gender, BMI, or ASA physical status between groups. The mean systolic blood pressure was 84.38 ± (7.45), mean diastolic blood pressure was 44.61 ± (7.38), mean ephedrine doses were 4.72 ± (4.10), and mean phenylephrine doses were 3.57 ± (4.40). Data did not support a statistically significant difference in lowest systolic blood pressure, lowest diastolic blood pressure, total phenylephrine dose, or total ephedrine dose between groups. Discussion: This study did not find an association between patients taking ACE inhibitors and increased requirements of vasopressors, lower systolic blood pressure, or lower diastolic blood pressure. The results of this current study are inconsistent with existing literature and could be explained by the retrospective nature of the study, small sample size, and only one hospital network used for patients. There were several limitations identified and discussed in this study. Conclusion: In this study, the use of ACE inhibitors the morning of surgery was not associated with more doses of vasopressor medications, lower systolic blood pressure, or lower diastolic blood pressure in patients undergoing PLIF. Implications/Recommendations: This study provided clinical relevance to anesthesia practitioners, researchers, and physicians about the use of ACE inhibitors for patients undergoing PLIF. Knowledge of ACE inhibitors and their effects help anesthesia providers customize the anesthetic to optimize patient safety

Inference of epidemiological parameters from household stratified data

We consider a continuous-time Markov chain model of SIR disease dynamics with two levels of mixing. For this so-called stochastic households model, we provide two methods for inferring the model parameters---governing within-household transmission, recovery, and between-household transmission---from data of the day upon which each individual became infectious and the household in which each infection occurred, as would be available from first few hundred studies. Each method is a form of Bayesian Markov Chain Monte Carlo that allows us to calculate a joint posterior distribution for all parameters and hence the household reproduction number and the early growth rate of the epidemic. The first method performs exact Bayesian inference using a standard data-augmentation approach; the second performs approximate Bayesian inference based on a likelihood approximation derived from branching processes. These methods are compared for computational efficiency and posteriors from each are compared. The branching process is shown to be an excellent approximation and remains computationally efficient as the amount of data is increased

Total Synthesis of the EF Fragment of Spongistatin 1 en Route to a Spongistatin 1 Analog

A major goal of the Leighton group is the synthesis of biologically relevant polyketide natural products. Among the most potent and chemically intriguing member of this class is spongistatin 1. This molecule has interested biologists and chemists for more than two decades. In this thesis, we report a highly practical and efficient synthesis of the EF fragment of spongistatin 1. This relied on the rapid introduction of a complex stereochemical array using double cross-metathesis/Sharpless asymmetric dihydroxylation reactions to quickly build the F-ring of spongistatin. The six contiguous stereocenters of the F-ring were established in just five steps. A new one-pot asymmetric strained-silane mediated allylation was developed that was greatly improved over previous methods in regards to practicality and substrate scope. This methodology was used to introduce the sensitive chlorodiene side chain. Finally, completion of the EF fragment led to the synthesis of a spongistatin 1 analog, using our previously developed redesigned ABCD fragment

Pandatopia: a novel with a critical commentary, TEOTWAWKI

Pandatopia: a novel with a critical commentary, TEOTWAWKI comprises a novel of my own creation, alongside a commentary that reflects on aspects of the creative process and aims to contextualise my work within the genre of Science Fiction. Pandatopia is set in a world where half the global population have been deliberately Changed into panda people by a gene-altering virus. Now normal unchanged humans are adapting to life alongside their super intelligent pandafied neighbours, often living as second-class citizens in a world now being shaped by panda-kind. The novel follows the journey of Megan – a panda person who began life not as a human, but as a giant panda – as she attempts to defend the remnants of humanity from an imminent threat. Megan has uncovered a plot to eradicate the remaining unchanged humans from the world, and believes that her own genetic material is key to the plotters’ machinations. She sets out to find others like her, Changed giant pandas who can take the form of bear or biped at will, in order to prevent them – and their DNA – from falling into the wrong hands. One of these beings is her brother, Alpha, who has since become the new Emperor of China. Megan is accompanied by an unchanged human named Jen and a panda person called James. She is also aided by a magpie known as “the Dave”, leader of his murder, who begins building a global empire of his own as they progress around the world. TEOTWAWKI explores the central themes of the novel alongside the work of contemporary SF writers and critical theorists. It also considers aspects of the process of composition, covering some of the events and experiences that inspired and informed the development of my novum, to frame the artistic nature of the primary text

The historicity of things: a study in the philosophy of Samuel Alexander

There is no part of Alexander's system which he anywhere explicitly characterises as a "philosophy of history"

A Replication and Cross-Validation of Hakes and Sauer\u27s An Economic Evaluation of the Moneyball Hypothesis

This paper replicates and cross-validates the econometric models presented by Hakes and Sauer in “An Economic Evaluation of the Moneyball Hypothesis.” The authors suggest an inefficiency in the major league baseball player market leading up to the publishing of Michael Lewis’s Moneyball. Through the usage of basic econometric methods, Hakes and Sauer (2006) determined that while on-base and slugging percentage were improperly valued prior to the book’s release in 2003, the inefficiency was corrected soon after. This study is successful in replicating the results produced by Hakes and Sauer, as well as cross-validating their findings with an agent-based model. However, after extending their work with new and current data, the external validity of their model is brought into question. Although major league baseball teams properly valued on-base and slugging percentage following the release of Moneyball, this correction no longer holds when examining data beyond the 2004 season

An Induced Natural Selection Heuristic for Finding Optimal Bayesian Experimental Designs

Bayesian optimal experimental design has immense potential to inform the collection of data so as to subsequently enhance our understanding of a variety of processes. However, a major impediment is the difficulty in evaluating optimal designs for problems with large, or high-dimensional, design spaces. We propose an efficient search heuristic suitable for general optimisation problems, with a particular focus on optimal Bayesian experimental design problems. The heuristic evaluates the objective (utility) function at an initial, randomly generated set of input values. At each generation of the algorithm, input values are "accepted" if their corresponding objective (utility) function satisfies some acceptance criteria, and new inputs are sampled about these accepted points. We demonstrate the new algorithm by evaluating the optimal Bayesian experimental designs for the previously considered death, pharmacokinetic and logistic regression models. Comparisons to the current "gold-standard" method are given to demonstrate the proposed algorithm as a computationally-efficient alternative for moderately-large design problems (i.e., up to approximately 40-dimensions)

Calculation of disease dynamics in a population of households

Early mathematical representations of infectious disease dynamics assumed a single, large, homogeneously mixing population. Over the past decade there has been growing interest in models consisting of multiple smaller subpopulations (households, workplaces, schools, communities), with the natural assumption of strong homogeneous mixing within each subpopulation, and weaker transmission between subpopulations. Here we consider a model of SIRS (susceptible-infectious-recovered-suscep​tible) infection dynamics in a very large (assumed infinite) population of households, with the simplifying assumption that each household is of the same size (although all methods may be extended to a population with a heterogeneous distribution of household sizes). For this households model we present efficient methods for studying several quantities of epidemiological interest: (i) the threshold for invasion; (ii) the early growth rate; (iii) the household offspring distribution; (iv) the endemic prevalence of infection; and (v) the transient dynamics of the process. We utilize these methods to explore a wide region of parameter space appropriate for human infectious diseases. We then extend these results to consider the effects of more realistic gamma-distributed infectious periods. We discuss how all these results differ from standard homogeneous-mixing models and assess the implications for the invasion, transmission and persistence of infection. The computational efficiency of the methodology presented here will hopefully aid in the parameterisation of structured models and in the evaluation of appropriate responses for future disease outbreaks