3,207 research outputs found
ObsErvatioNal prospective multicenter stuDy tO characterize the cLinical ANd DiagnoStiC feAtures of endocarditis in the contemPorary Era (ENDO-LANDSCAPE study): rationale and design
No full textBackground: Recent developments in the management of valvular heart disease and heart failure have resulted in a dramatic increase in percutaneous valve procedures and implanted devices. We hypothesize that this has impacted the epidemiology, diagnosis, and management of endocarditis. Methods: The obsErvatioNal prospective multicenter stuDy tO characterize the cLinical ANd DiagnoStiC feAtures of endocarditis in the contemPorary Era (ENDO-LANDSCAPE study) is an observational, multicenter, and international study aimed to examine the epidemiology of endocarditis in the contemporary era. The study will constitute of a retrospective arm for the determination of the sample size of the prospective arm, where cases of endocarditis between 2016 to 2022 at three tertiary referral institutions will be analyzed. The prospective arm will examine all consecutive patients referred for an echocardiography with a suspected or confirmed diagnosis of endocarditis, and their clinical course followed up over 12 months for adverse outcomes. The primary aim of the study will be to characterize the epidemiology of endocarditis, focusing on patients with prosthetic or implanted devices. The secondary aims would be: the appropriateness of the requests for first-line echocardiographic imaging in exclusion of endocarditis; the role of other imaging modalities in the diagnosis of endocarditis; and the impact of a specialized endocarditis team on outcomes. Implications: The results of the ENDO-LANDSCAPE study will provide a contemporary update of the epidemiological trends in endocarditis. The data generated from this study would be useful in informing future clinical practice, potentially guiding future diagnostic and treatment algorithms in patients with endocarditis
Increasing Distributed Generation Penetration using Soft Normally-Open Points
No full textThis paper considers the effects of various voltage control solutions on facilitating an increase in allowable levels of distributed generation installation before voltage violations occur. In particular, the voltage control solution that is focused on is the implementation of `soft' normally-open points (SNOPs), a term which refers to power electronic devices installed in place of a normally-open point in a medium-voltage distribution network which allows for control of real and reactive power flows between each end point of its installation sites. While other benefits of SNOP installation are discussed, the intent of this paper is to determine whether SNOPs are a viable alternative to other voltage control strategies for this particular application. As such, the SNOPs ability to affect the voltage profile along feeders within a distribution system is focused on with other voltage control options used for comparative purposes. Results from studies on multiple network models with varying topologies are presented and a case study which considers economic benefits of increasing feasible DG penetration is also given
Engineering the fusion machinery core of SARS-CoV-2 spike protein for vaccine immunogen design
No full textSubmission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2025-10-19 without embargo termsThe student, Timothy James Tan, accepted the attached license on 2025-02-11 at 11:43.The student, Timothy James Tan, submitted this Dissertation for approval on 2025-02-11 at 11:46.This Dissertation was approved for publication on 2025-02-13 at 16:22.DSpace SAF Submission Ingestion Package generated from Vireo submission #21613 on 2025-10-19 at 18:17:14The emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 prompted the rapid development and deployment of vaccines harboring the spike protein of the virus. For vaccines to be effective, the spike protein immunogen required engineering into its prefusion-stabilizing conformation to elicit protective antibodies that primarily bind the spike receptor-binding domain (RBD), in addition to the spike’s N-terminal domain, and fusion machinery core. I showed that natural SARS-CoV-2 infection or vaccination with SARS-CoV-2 spike protein elicits protective, public antibodies encoded by IGHV3-53/3-66 with unique amino acid sequence signatures. Eliciting these public RBD antibodies is an alluring goal of vaccination for prophylactic protection among majority of the human population. To this end, I developed a systematic and unbiased high-throughput method of identifying prefusion-stabilizing mutations in the fusion machinery core of SARS-CoV-2 spike protein that will render the RBD intact. By combining saturation mutagenesis, mammalian cell display, a cell-based fusion assay, fluorescence-activated cell sorting, and deep sequencing, I identified several mutations, in addition to the two proline mutations used in currently approved vaccines, that lock the spike protein in its prefusion conformation. Biophysical characterization revealed that a D994Q mutation in the first heptad repeat prevented the complete unfolding of the spike trimer by forming an additional intra-protomer hydrogen bond. To develop vaccines that can target future variants, escape mutants of the spike protein need to be identified and characterized. Public antibodies encoded by IGHV1-69 and IGKV3-11 target the highly conserved S2 subunit containing the fusion machinery core of SARS-CoV-2. However, deep mutational scanning experiments showed that the D950N and Q954H mutations found in Delta and Omicron variants, respectively, weaken the binding of public antibodies to spike, and consequently, decrease protection in vivo. These results highlight that an innovative, high-throughput, deep mutational scanning-based method can accelerate vaccine immunogen engineering by systematically interrogating each mutation, and antigenic drift of immunogenic proteins provide a significant challenge for the proactive development of universal vaccines
Suite no. 3, BWV 1009
No full textMore Author/Title Info: Johann Sebastian Bach ; edition for double bass by Timothy Cobb.
Uniform Title: Suites, cello, BWV 1009, C major; arranged
Physical Description: 2 scores (8 pages) ; 28 c
Romance, op. 50
No full textMore Author/Title Info: Ludwig van Beethoven ; editions for double bass and piano by Timothy Cobb.
Uniform Title: Romances, violin, orchestra, op. 50, F major; arranged
Physical Description: 2 scores (10 pages) + 2 parts (4 pages) ; 28 c
Evaluating Research Impact through Open Access to Scholarly Communication
No full textScientific research is a competitive business – in order to secure funding, promotion and tenure researchers must demonstrate their work has impact in their field. To maximise impact researchers undertake high priority research, aim to get results first, and publish in the highest impact journals. The Internet now presents a new opportunity to the scholarly author seeking higher impact: s/he can now make their work instantly accessible on the Web through author self-archiving. This growing body of open access literature (coupled with new publishing models that make journals available for-free to the reader) maximises research impact by maximising the number of people who can read it, and making it available sooner. Open access also provides a new opportunity for bibliometric research. This thesis describes the relatively recent phenomenon of open access to research literature, tools that were built to collect and analyse that literature, and the results of analyses of the effect of open access and its effect on author behaviour. It shows that articles self-archived by authors receive between 50-250% more citations, that rapid pre-printing on the Web has dramatically reduced the peak citation rate from over a year to virtually instant and how citation-impact – now widely used for evaluation – can be expanded to include a new web metric of download impact
2000 Commencement Address: G. Timothy Johnson, M.D.
No full textTimothy Johnson, M.D., medical editor for ABC News will deliver the principal address and receive an honorary degree at the 154th commencement exercises at the College of the Holy Cross on Friday, May 26, beginning at 10:30 a.m. at Fitton Field.
Johnson, one of the nation’s leading medical communicators of health care information, has provided commentary on medical problems and answers for viewers since 1975. In addition to commentary on Good Morning America, Johnson provides on-air analysis of medical news for World News Tonight, Nightline and 20/20. He consults with ABC News regardingcoverage of medical news. He is also medical editor for WCVB-TV, Channel 5 in Boston.
Johnson holds joint positions in medicine at Harvard University and Massachusetts General Hospital in Boston. He is the founding editor of the Harvard Medical School Health Letter and co-editor of the Harvard Medical School Health Letter Book. He is also coeditor of the book, “Your Good Health,” published by Harvard Press, as well as co-author with former US Surgeon General Dr. C. Everett Koop of the book, “Let’s Talk,” published by Zondervan in 1992.
He originally intended to join the ministry and graduated from the North Park Seminary in 1963. Two years later he decided to enter medicine. Johnson, who is a Phi Beta Kappa graduate of Augustana College, graduated summa cum laude from Albany Medical College and holds a master’s degree in public health from Harvard University. Johnson served as an assisting minister at the Community Covenant Church in West Peabody, Mass.https://crossworks.holycross.edu/commence_address/1012/thumbnail.jp
The Redeemer in an "irredeemable text" (1 Timothy 2:9-15)
No full textIn the ongoing debate about the meaning of 1 Timothy 2:9-15 some have branded it an "irredeemable text of terror" while for others it contains "God's eternal design for men and women." In this article it is argued that both these views fail to give due cognisance to the declared intention of the author of this passage. It is demonstrated how, in a strategy of accommodation, the author uses traditional material to further his (and God's) aim to save all people by bringing them to the knowledge of the truth about Jesus Christ, the Redeemer. In the final hermeneusis it is proposed that the legitimate and authoritative application of 1 Timothy 2:9-15 lies in its intended soteriological focus and strategy and not in the endorsement of any social or socio-political agenda
Design of experiments with mixed effects and discrete responses plus related topics
No full textFor certain types of experiment, the response cannot be adequately modelled using a normal distribution. When this is the case, it is common to use a Generalised Linear Model (GLM) to analyse the data. Such models allow us to fit a wide range of response distributions including Bernoulli and Poisson.If responses in the same block are correlated, it may be appropriate to model the impact of blocking using random effects. The GLM can be extended in several ways to include random effects; both Generalised Linear Mixed Models (GLMMs) and Hierarchical Generalised Linear Models (HGLMs) are common examples of such extensions. Another example is a random intercept model for a binary response bioassay study with repeated measurements on heterogeneous individuals. The latter model is related to a GLMM but not strictly within that class.Obtaining designs for non-normal models with random effects is complicated by the fact that the information matrix, on which most optimality criteria are based, is computationally expensive to evaluate. Indeed, if one computes naively, the search for a typical optimal GLMM design is likely to take several months.When estimating GLMMs, it is common to use analytical approximations such as marginal quasi-likelihood (MQL) and penalised quasi-likelihood (PQL) in place of full maximum likelihood estimation. In Chapters 2 and 3, we consider the use of such computationally cheap approximations to construct surrogates for the information matrix when producing optimal designs. These reduce the computational burden substantially, enabling us to obtain designs within a practical time frame. The accuracy of the analytical approximations is explored through the use of a detailed computational approximation, which enables us to compute the optimal maximum likelihood design in the case where there are at most two points per block. It is found that one of the analytical approximations appears to perform consistently better than the others for the purposes of producing designs.In Chapters 4 and 5, designs for an individual variation bioassay model are obtained in the cases where (i) there is a single observation, or (ii) there are multiple observations, per individual. In the former case, designs on the basis of both maximum likelihood and analytical approximations are found and compared. In the multiple observation case, a restriction on the design space enables optimal designs to be computed using a computational approximation related to that for GLMMs. This involves extensive precomputation of numerical integrals.In Chapter 6 designs for HGLMs are studied using a computationally inexpensive asymptotic approximation to the variance-covariance matrix of the parameter estimators. This allows us to derive designs which are also efficient for the estimation of the random effects.Throughout, the dependence of the optimal design on the unknown values of the model parameters is addressed through the use of Bayesian methods, which codify uncertainty about the parameter values using a prior distribution. We often assess the performance of the designs obtained from the optimisation of a Bayesian objective function in terms of the distribution on the local efficiencies which is induced by the prior distribution.When the parameter space contains degenerate values, there is a problem with potential non-convergence of the Bayesian objective function used to select designs. This issue is explored in depth in Chapter 7, and results are obtained for a number of standard models
INDIGENOUS PEOPLES OF THE BRITISH DOMINIONS AND THE FIRST WORLD WAR/ Timothy C. Winegard
No full textTimothy Winegard saw active duty in the Canadian Reserve Force from 2001 to 2010 and served on detachment duty to the British Army for a two-year period. He obtained various academic degrees from 1999 onwards, among others a BA Hons degree in History and an MA in War Studies. The book under discussion here is the third work by this author. Other publications from this author include Oka: A convergence of cultures and the Canadian forces (2008), For King and Kanata (2011), and the latest work entitled Indigenous peoples of the British dominions and the First World War (2012).</p
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