Bayesian Uncertainty Analysis and Decision Support for Complex Models of Physical Systems with Application to Production Optimisation of Subsurface Energy Resources

Important decision making problems are increasingly addressed using computer models for complex real world systems. However, there are major limitations to their direct use including: their complex structure; large numbers of inputs and outputs; the presence of many sources of uncertainty; which is further compounded by their long evaluation times. Bayesian methodology for the analysis of computer models has been extensively developed to perform inference for the physical systems. In this thesis, the Bayesian uncertainty analysis methodology is extended to provide robust decision support under uncertainty. Bayesian emulators are employed as a fast and efficient statistical approximation for computer models. We establish a hierarchical Bayesian emulation framework that exploits known constrained simulator behaviour in constituents of the decision support utility function. In addition, novel Bayesian emulation methodology is developed for computer models with structured partial discontinuities. We advance the crucial uncertainty quantification methodology to perform a robust decision analysis developing a technique to assess and remove linear transformations of the utility function induced by sources of uncertainty to which conclusions are invariant, as well as incorporating structural model discrepancy and decision implementation error. These are encompassed within a novel iterative decision support procedure which acknowledges utility function uncertainty resulting from the separation of the analysts and final decision makers to deliver a robust class of decisions, along with any additional information, for further consideration. The complete toolkit is successfully demonstrated via an application to the problem of optimal petroleum field development, including an international and commercially important benchmark challenge

The importance of sustained attention in early Alzheimer\u27s disease

Introduction: There is conflicting evidence regarding impairment of sustained attention in early Alzheimer\u27s disease (AD). We examine whether sustained attention is impaired and predicts deficits in other cognitive domains in early AD. Methods: Fifty-one patients with early AD (MMSE \u3e 18) and 15 healthy elderly controls were recruited. The sustained attention to response task (SART) was used to assess sustained attention. A subset of 25 patients also performed tasks assessing general cognitive function (ADAS-Cog), episodic memory (Logical memory scale, Paired Associates Learning), executive function (verbal fluency, grammatical reasoning) and working memory (digit and spatial span). Results: AD patients were significantly impaired on the SART compared to healthy controls (total error β = 19.75, p = 0.027). SART errors significantly correlated with MMSE score (Spearman\u27s rho = −0.338, p = 0.015) and significantly predicted deficits in ADAS-Cog (β = 0.14, p = 0.004). Discussions: Patients with early AD have significant deficits in sustained attention, as measured using the SART. This may impair performance on general cognitive testing, and therefore should be taken into account during clinical assessment, and everyday management of individuals with early AD. Copyright © 2016 John Wiley & Sons, Ltd

Anthracene Diphosphate Ligands for CdSe Quantum Dots; Molecular Design for Efficient Upconversion

Quantum dot (QD)-sensitized photon upconversion follows a multi-step energy transfer process from the QD to transmitter ligand to a soluble annihilator. Using a novel 10-R-anthracene-1,8-diphosphoric acid (R = octyl, 2-hexyldecyl, phenyl) ligand with high binding affinity for CdSe QD surfaces, we demonstrate a photon upconversion process that is limited by the transmitter to annihilator transfer efficiency. Using 1H NMR spectroscopy, we demonstrate that these bidentate diphosphate ligands rapidly and irreversibly displace two carboxylate ligands. These ligands mediate energy transfer from the photoexcited QDs to a triplet annihilator (1,10-diphenylanthracene), producing overall photon upconversion quantum efficiencies as high as 17%, the highest for QDs with no shells. Transient absorption spectroscopy shows that the anthracene dihydrogen phosphate (ADP) ligand supports a 3.4 fold longer triplet state lifetime compared to 9-anthracene carboxylic acid (299.9 ± 9.5 vs 88.2 ± 2.1 μs), increasing the probability of energy transfer

Assessing awareness in severe Alzheimer's disease

There is an urgent need to understand the nature of awareness in people with severe Alzheimer's disease (AD) to ensure effective person-centered care. Objective biomarkers of awareness validated in other clinical groups (e.g., anesthesia, minimally conscious states) offer an opportunity to investigate awareness in people with severe AD. In this article we demonstrate the feasibility of using Transcranial magnetic stimulation (TMS) combined with EEG, event related potentials (ERPs) and fMRI to assess awareness in severe AD. TMS-EEG was performed in six healthy older controls and three people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. People with severe AD demonstrated a PCIST around or below the threshold for consciousness, suggesting reduced capacity for consciousness. ERPs were recorded during a visual perception paradigm. In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. Using a validated fMRI movie-viewing task, independent component analysis in two healthy controls and one patient with severe AD revealed activation in auditory, visual and fronto-parietal networks. Activation patterns in fronto-parietal networks did not significantly correlate between the patient and controls, suggesting potential differences in conscious awareness and engagement with the movie. Although methodological issues remain, these results demonstrate the feasibility of using objective measures of awareness in severe AD. We raise a number of challenges and research questions that should be addressed using these biomarkers of awareness in future studies to improve understanding and care for people with severe AD

Understanding Alzheimer's disease as a disorder of consciousness.

People with Alzheimer's disease (AD) demonstrate a range of alterations in consciousness. Changes in awareness of cognitive deficit, self-awareness, and introspection are seen early in AD, and dysfunction of awareness and arousal progresses with increasing disease severity. However, heterogeneity of deficits between individuals and a lack of empirical studies in people with severe dementia highlight the importance of identifying and applying biomarkers of awareness in AD. Impairments of awareness in AD are associated with neuropathology in regions that overlap with proposed neural correlates of consciousness. Recent developments in consciousness science provide theoretical frameworks and experimental approaches to help further understand the conscious experience of people with AD. Recognition of AD as a disorder of consciousness is overdue, and important to both understand the lived experience of people with AD and to improve care

Star forming galaxies in the Hercules cluster: Halpha imaging of A2151

This paper presents the first results of an Halpha imaging survey of galaxies in the central regions of the A2151 cluster. A total of 50 sources were detected in Halpha. The morphologies of the 43 H$\alpha$ selected galaxies range from grand design spirals and interacting galaxies to blue compacts and tidal dwarfs or isolated extragalactic HII regions, spanning a range of magnitudes of -21 <= MB <= -12.5 mag. A comparison with the clusters Coma and A1367 and a sample of field galaxies has shown the presence of cluster galaxies with L(Halpha) lower than expected for their MB, a consecuence of the cluster environment. This fact results in differences in the L(Halpha) vs. EW(Halpha) and L(H\alpha) distributions of the clusters with respect to the field, and in cluster to cluster variations of these quantities, which we propose are driven by a global cluster property as the total mass. Overall, we conclude that both, the global cluster environment as well as the cluster merging history play a non negligible role in the integral star formation properties of clusters of galaxies.Comment: 38 pages, 11 figures. Accepted for publication in Astronomical Journa

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

An ethical framework for global vaccine allocation

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations

Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Leray, M., Wilkins, L. G. E., Apprill, A., Bik, H. M., Clever, F., Connolly, S. R., De Leon, M. E., Duffy, J. E., Ezzat, L., Gignoux-Wolfsohn, S., Herre, E. A., Kaye, J. Z., Kline, D. I., Kueneman, J. G., McCormick, M. K., McMillan, W. O., O’Dea, A., Pereira, T. J., Petersen, J. M., Petticord, D. F., Torchin, M. E., Thurber, R. V., Videvall, E., Wcislo, W. T., Yuen, B., Eisen, J. A. . Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution. Plos Biology, 19(8), (2021): e3001322, https://doi.org/10.1371/journal.pbio.3001322.Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host’s physiological capacities; however, the identity and functional role(s) of key members of the microbiome (“core microbiome”) in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems’ capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts’ plastic and adaptive responses to environmental change requires (i) recognizing that individual host–microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.Financial support for the workshop was provided by grant GBMF5603 (https://doi.org/10.37807/GBMF5603) from the Gordon and Betty Moore Foundation (W.T. Wcislo, J.A. Eisen, co-PIs), and additional funding from the Smithsonian Tropical Research Institute and the Office of the Provost of the Smithsonian Institution (W.T. Wcislo, J.P. Meganigal, and R.C. Fleischer, co-PIs). JP was supported by a WWTF VRG Grant and the ERC Starting Grant 'EvoLucin'. LGEW has received funding from the European Union’s Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Marie Sklodowska-Curie Grant Agreement No. 101025649. AO was supported by the Sistema Nacional de Investigadores (SENACYT, Panamá). A. Apprill was supported by NSF award OCE-1938147. D.I. Kline, M. Leray, S.R. Connolly, and M.E. Torchin were supported by a Rohr Family Foundation grant for the Rohr Reef Resilience Project, for which this is contribution #2. This is contribution #85 from the Smithsonian’s MarineGEO and Tennenbaum Marine Observatories Network.