Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial

OBJECTIVES: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD).

DESIGN: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard).

SETTING: Internet-based application.

PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care.

INTERVENTIONS: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes.

MAIN OUTCOME MEASURES: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions.

RESULTS: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists.

CONCLUSIONS: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals.

TRIAL REGISTRATION NUMBER: ISRCTN07479761; pre-results registration.

Screened Hybrid Exact Exchange Correction Scheme for Adsorption Energies on Perovskite Oxides

The bond formation between an oxide surface and oxygen, which is of importance for numerous surface reactions including catalytic reactions, is investigated within the framework of hybrid density functional theory that includes nonlocal Fock exchange. We show that there exists a linear correlation between the adsorption energies of oxygen on LaMO3 (M = Sc–Cu) surfaces obtained using a hybrid functional (e.g., Heyd–Scuseria–Ernzerhof) and those obtained using a semilocal density functional (e.g., Perdew–Burke–Ernzerhof) through the magnetic properties of the bulk phase as determined with a hybrid functional. The energetics of the spin-polarized surfaces follows the same trend as corresponding bulk systems, which can be treated at a much lower computational cost. The difference in adsorption energy due to magnetism is linearly correlated to the magnetization energy of bulk, that is, the energy difference between the spin-polarized and the non-spin-polarized solutions. Hence, one can estimate the correction ...

Aspects of Chiral Symmetry Breaking in Lattice QCD

Thesis (Ph.D.)--University of Washington, 2016-08

Solar magnetic carpet II: coronal interactions of small-scale magnetic fields

This paper is the second in a series of studies working towards constructing a realistic, evolving, non-potential coronal model for the solar magnetic carpet. In the present study, the interaction of two magnetic elements is considered. Our objectives are to study magnetic energy build-up, storage and dissipation as a result of emergence, cancellation, and flyby of these magnetic elements. In the future these interactions will be the basic building blocks of more complicated simulations involving hundreds of elements. Each interaction is simulated in the presence of an overlying uniform magnetic field, which lies at various orientations with respect to the evolving magnetic elements. For these three small-scale interactions, the free energy stored in the field at the end of the simulation ranges from 0.2 – 2.1×1026 ergs, whilst the total energy dissipated ranges from 1.3 – 6.3×1026 ergs. For all cases, a stronger overlying field results in higher energy storage and dissipation. For the cancellation and emergence simulations, motion perpendicular to the overlying field results in the highest values. For the flyby simulations, motion parallel to the overlying field gives the highest values. In all cases, the free energy built up is sufficient to explain small-scale phenomena such as X-ray bright points or nanoflares. In addition, if scaled for the correct number of magnetic elements for the volume considered, the energy continually dissipated provides a significant fraction of the quiet Sun coronal heating budget.

Spectral Frame Analysis and Learning through Graph Structure

This dissertation investigates the connection between spectral analysis and frame theory. When considering the spectral properties of a frame, we present a few novel results relating to the spectral decomposition. We first show that scalable frames have the property that the inner product of the scaling coefficients and the eigenvectors must equal the inverse eigenvalues. From this, we prove a similar result when an approximate scaling is obtained. We then focus on the optimization problems inherent to the scalable frames by first showing that there is an equivalence between scaling a frame and optimization problems with a non-restrictive objective function. Various objective functions are considered, and an analysis of the solution type is presented. For linear objectives, we can encourage sparse scalings, and with barrier objective functions, we force dense solutions. We further consider frames in high dimensions, and derive various solution techniques. From here, we restrict ourselves to various frame classes, to add more specificity to the results. Using frames generated from distributions allows for the placement of probabilistic bounds on scalability. For discrete distributions (Bernoulli and Rademacher), we bound the probability of encountering an ONB, and for continuous symmetric distributions (Uniform and Gaussian), we show that symmetry is retained in the transformed domain. We also prove several hyperplane-separation results. With the theory developed, we discuss graph applications of the scalability framework. We make a connection with graph conditioning, and show the in-feasibility of the problem in the general case. After a modification, we show that any complete graph can be conditioned. We then present a modification of standard PCA (robust PCA) developed by Cand\`es, and give some background into Electron Energy-Loss Spectroscopy (EELS). We design a novel scheme for the processing of EELS through robust PCA and least-squares regression, and test this scheme on biological samples. Finally, we take the idea of robust PCA and apply the technique of kernel PCA to perform robust manifold learning. We derive the problem and present an algorithm for its solution. There is also discussion of the differences with RPCA that make theoretical guarantees difficult.

The functional structure of the sentence: evidence from non-finite clauses

Non-finite clauses are sentential constituents with a verbal head that lacks a morphological specification for tense and agreement. In this paper I contend that these clauses are defective not only morphologically but also syntactically, in the sense that they all lack some of the functional categories that make up a full sentence. In particular I argue that to-infinitive clauses, gerund(ive) clauses and participial clauses differ among themselves, and with respect to other subordinate clauses, in the degree of structural defectiveness they display, which goes from the almost complete functional structure of the infinitive to the maximal degree of syntactic truncation of participial clauses (analyzed here as verbal small clauses). I also show the significant parallelism that exists in this respect between English and Spanish non-finite clauses, pointing to the implication this may have for a cross-linguistic approach to the cartography of syntactic structures.

Genome-scale analysis of the non-cultivable Treponema pallidum reveals extensive within-patient genetic variation

Insights into the genomic adaptive traits of Treponema pallidum, the causative bacterium of syphilis, have long been hampered due to the absence of in vitro culture models and the constraints associated with its propagation in rabbits. Here, we have bypassed the culture bottleneck by means of a targeted strategy never applied to uncultivable bacterial human pathogens to directly capture whole-genome T. pallidum data in the context of human infection. This strategy has unveiled a scenario of discreet T. pallidum interstrain single-nucleotide-polymorphism-based microevolution, contrasting with a rampant within-patient genetic heterogeneity mainly targeting multiple phase-variable loci and a major antigen-coding gene (tprK). TprK demonstrated remarkable variability and redundancy, intra- and interpatient, suggesting ongoing parallel adaptive diversification during human infection. Some bacterial functions (for example, flagella- and chemotaxis-associated) were systematically targeted by both inter- and intrastrain single nucleotide polymorphisms, as well as by ongoing within-patient phase variation events. Finally, patient-derived genomes possess mutations targeting a penicillin-binding protein coding gene (mrcA) that had never been reported, unveiling it as a candidate target to investigate the impact on the susceptibility to penicillin. Our findings decode the major genetic mechanisms by which T. pallidum promotes immune evasion and survival, and demonstrate the exceptional power of characterizing evolving pathogen subpopulations during human infection.

Guided Migration and Collective Behavior: Cell Dynamics during Cancer Progression

This dissertation focuses on gaining understanding of cell migration and collective behavior through a combination of experiment, analysis, and modeling techniques. Cell migration is a ubiquitous process that plays an important role during embryonic development and wound healing as well as in diseases like cancer, which is a particular focus of this work. As cancer cells become increasingly malignant, they acquire the ability to migrate away from the primary tumor and spread throughout the body to form metastatic tumors. During this process, changes in gene expression and the surrounding tumor environment can lead to changes in cell migration characteristics. In this thesis, I analyze how cells are guided by the texture of their environment and how cells cooperate with their neighbors to move collectively. The emergent properties of collectively moving groups are a particular focus of this work as collective cell dynamics are known to change in diseases such as cancer. The internal machinery for cell migration involves polymerization of the actin cytoskeleton to create protrusions that---in coordination with retraction of the rear of the cell---lead to cell motion. This actin machinery has been previously shown to respond to the topography of the surrounding surface, leading to guided migration of amoeboid cells. Here we show that epithelial cells on nanoscale ridge structures also show changes in the morphology of their cytoskeletons; actin is found to align with the ridge structures. The migration of the cells is also guided preferentially along the ridge length. These ridge structures are on length scales similar to those found in tumor microenvironments and as such provide a system for studying the response of the cells' internal migration machinery to physiologically relevant topographical cues. In addition to sensing surface topography, individual cells can also be influenced by the pushing and pulling of neighboring cells. The emergent properties of collectively migrating cells show interesting dynamics and are relevant for cancer progression, but have been less studied than the motion of individual cells. We use Particle Image Velocimetry (PIV) to extract the motion of a collectively migrating cell sheet from time lapse images. The resulting flow fields allow us to analyze collective behavior over multiple length and time scales. To analyze the connection between individual cell properties and collective migration behavior, we compare experimental flow fields with the migration of simulated cell groups. Our collective migration metrics allow for a quantitative comparison between experimental and simulated results. This comparison shows that tissue-scale decreases in collective behavior can result from changes in individual cell activity without the need to postulate the existence of subpopulations of leader cells or global gradients. In addition to tissue-scale trends in collective behavior, the migration of cell groups includes localized dynamic features such as cell rearrangements. An individual cell may smoothly follow the motion of its neighbors (affine motion) or move in a more individualistic manner (non-affine motion). By decomposing individual motion into both affine and non-affine components, we measure cell rearrangements within a collective sheet. Finally, finite-time Lyapunov exponent (FTLE) values capture the stretching of the flow field and reflect its chaotic character. Applying collective migration analysis techniques to experimental data on both malignant and non-malignant human breast epithelial cells reveals differences in collective behavior that are not found from analyzing migration speeds alone. Non-malignant cells show increased cooperative motion on long time scales whereas malignant cells remain uncooperative as time progresses. Combining multiple analysis techniques also shows that these two cell types differ in their response to a perturbation of cell-cell adhesion through the molecule E-cadherin. Non-malignant MCF10A cells use E-cadherin for short time coordination of collective motion, yet even with decreased E-cadherin expression, the cells remain coordinated over long time scales. In contrast, the migration behavior of malignant and invasive MCF10CA1a cells, which already shows decreased collective dynamics on both time scales, is insensitive to the change in E-cadherin expression.

Guided Migration and Collective Behavior: Cell Dynamics during Cancer Progression

This dissertation focuses on gaining understanding of cell migration and collective behavior through a combination of experiment, analysis, and modeling techniques. Cell migration is a ubiquitous process that plays an important role during embryonic development and wound healing as well as in diseases like cancer, which is a particular focus of this work. As cancer cells become increasingly malignant, they acquire the ability to migrate away from the primary tumor and spread throughout the body to form metastatic tumors. During this process, changes in gene expression and the surrounding tumor environment can lead to changes in cell migration characteristics. In this thesis, I analyze how cells are guided by the texture of their environment and how cells cooperate with their neighbors to move collectively. The emergent properties of collectively moving groups are a particular focus of this work as collective cell dynamics are known to change in diseases such as cancer. The internal machinery for cell migration involves polymerization of the actin cytoskeleton to create protrusions that---in coordination with retraction of the rear of the cell---lead to cell motion. This actin machinery has been previously shown to respond to the topography of the surrounding surface, leading to guided migration of amoeboid cells. Here we show that epithelial cells on nanoscale ridge structures also show changes in the morphology of their cytoskeletons; actin is found to align with the ridge structures. The migration of the cells is also guided preferentially along the ridge length. These ridge structures are on length scales similar to those found in tumor microenvironments and as such provide a system for studying the response of the cells' internal migration machinery to physiologically relevant topographical cues. In addition to sensing surface topography, individual cells can also be influenced by the pushing and pulling of neighboring cells. The emergent properties of collectively migrating cells show interesting dynamics and are relevant for cancer progression, but have been less studied than the motion of individual cells. We use Particle Image Velocimetry (PIV) to extract the motion of a collectively migrating cell sheet from time lapse images. The resulting flow fields allow us to analyze collective behavior over multiple length and time scales. To analyze the connection between individual cell properties and collective migration behavior, we compare experimental flow fields with the migration of simulated cell groups. Our collective migration metrics allow for a quantitative comparison between experimental and simulated results. This comparison shows that tissue-scale decreases in collective behavior can result from changes in individual cell activity without the need to postulate the existence of subpopulations of leader cells or global gradients. In addition to tissue-scale trends in collective behavior, the migration of cell groups includes localized dynamic features such as cell rearrangements. An individual cell may smoothly follow the motion of its neighbors (affine motion) or move in a more individualistic manner (non-affine motion). By decomposing individual motion into both affine and non-affine components, we measure cell rearrangements within a collective sheet. Finally, finite-time Lyapunov exponent (FTLE) values capture the stretching of the flow field and reflect its chaotic character. Applying collective migration analysis techniques to experimental data on both malignant and non-malignant human breast epithelial cells reveals differences in collective behavior that are not found from analyzing migration speeds alone. Non-malignant cells show increased cooperative motion on long time scales whereas malignant cells remain uncooperative as time progresses. Combining multiple analysis techniques also shows that these two cell types differ in their response to a perturbation of cell-cell adhesion through the molecule E-cadherin. Non-malignant MCF10A cells use E-cadherin for short time coordination of collective motion, yet even with decreased E-cadherin expression, the cells remain coordinated over long time scales. In contrast, the migration behavior of malignant and invasive MCF10CA1a cells, which already shows decreased collective dynamics on both time scales, is insensitive to the change in E-cadherin expression.

The Development of Calibrants through Characterization of Volatile Organic Compounds from Peroxide Based Explosives and a Non-target Chemical Calibration Compound

Detection canines represent the fastest and most versatile means of illicit material detection. This research endeavor in its most simplistic form is the improvement of detection canines through training, training aids, and calibration. This study focuses on developing a universal calibration compound for which all detection canines, regardless of detection substance, can be tested daily to ensure that they are working with acceptable parameters. Surrogate continuation aids (SCAs) were developed for peroxide based explosives along with the validation of the SCAs already developed within the International Forensic Research Institute (IFRI) prototype surrogate explosives kit. Storage parameters of the SCAs were evaluated to give recommendations to the detection canine community on the best possible training aid storage solution that minimizes the likelihood of contamination. Two commonly used and accepted detection canine imprinting methods were also evaluated for the speed in which the canine is trained and their reliability. As a result of the completion of this study, SCAs have been developed for explosive detection canine use covering: peroxide based explosives, TNT based explosives, nitroglycerin based explosives, tagged explosives, plasticized explosives, and smokeless powders. Through the use of these surrogate continuation aids a more uniform and reliable system of training can be implemented in the field than is currently used today. By examining the storage parameters of the SCAs, an ideal storage system has been developed using three levels of containment for the reduction of possible contamination. The developed calibration compound will ease the growing concerns over the legality and reliability of detection canine use by detailing the daily working parameters of the canine, allowing for Daubert rules of evidence admissibility to be applied. Through canine field testing, it has been shown that the IFRI SCAs outperform other commercially available training aids on the market. Additionally, of the imprinting methods tested, no difference was found in the speed in which the canines are trained or their reliability to detect illicit materials. Therefore, if the recommendations discovered in this study are followed, the detection canine community will greatly benefit through the use of scientifically validated training techniques and training aids.

Effects of small scale non-mechanised forest management and high impact and mechanised forest management on the forest dynamics and growth of the residual trees.

This study was perfonned in PSPs located at the CPAr-ACRE EMORAPA expcrirnental area and at the PC Peixoto management areas. AI CPA F-ACR E the managed area was meehanically exploited in 1992 and at PC Peixoto animal traction was used to extract the planks.

Spatial scale effects of sampling on the interpolation of species distribution models in the southwestern Amazon.

Knowledge of the geographical distribution of timber tree species in the Amazon is still scarce. This is especially true at the local level, thereby limiting natural resource management actions. Forest inventories are key sources of information on the occurrence of such species. However, areas with approved forest management plans are mostly located near access roads and the main industrial centers. The present study aimed to assess the spatial scale effects of forest inventories used as sources of occurrence data in the interpolation of potential species distribution models. The occurrence data of a group of six forest tree species were divided into four geographical areas during the modeling process. Several sampling schemes were then tested applying the maximum entropy algorithm, using the following predictor variables: elevation, slope, exposure, normalized difference vegetation index (NDVI) and height above the nearest drainage (HAND). The results revealed that using occurrence data from only one geographical area with unique environmental characteristics increased both model overfitting to input data and omission error rates. The use of a diagonal systematic sampling scheme and lower threshold values led to improved model performance. Forest inventories may be used to predict areas with a high probability of species occurrence, provided they are located in forest management plan regions representative of the environmental range of the model projection area.

Excitonic properties of transition metal oxide perovskites and workflow automatization of GW schemes

The Many-Body-Perturbation Theory approach is among the most successful theoretical frameworks for the study of excited state properties. It allows to describe the excitonic interactions, which play a fundamental role in the optical response of insulators and semiconductors. The first part of the thesis focuses on the study of the quasiparticle, optical and excitonic properties of \textit{bulk} Transition Metal Oxide (TMO) perovskites using a G$_0$W$_0$+Bethe Salpeter Equation (BSE) approach. A representative set of 14 compounds has been selected, including 3d, 4d and 5d perovskites. An approximation of the BSE scheme, based on an analytic diagonal expression for the inverse dielectric function, is used to compute the exciton binding energies and is carefully bench-marked against the standard BSE results. In 2019 an important breakthrough has been achieved with the synthesis of ultrathin SrTiO3 films down to the monolayer limit. This allows us to explore how the quasiparticle and optical properties of SrTiO3 evolve from the bulk to the two-dimensional limit. The electronic structure is computed with G0W0 approach: we prove that the inclusion of the off-diagonal self-energy terms is required to avoid non-physical band dispersions. The excitonic properties are investigated beyond the optical limit at finite momenta. Lastly a study of the under pressure optical response of the topological nodal line semimetal ZrSiS is presented, in conjunction with the experimental results from the group of Prof. Dr. Kuntscher of the Augsburg University. The second part of the thesis discusses the implementation of a workflow to automate G$_0$W$_0$ and BSE calculations with the VASP software. The workflow adopts a convergence scheme based on an explicit basis-extrapolation approach [J. Klimeš \textit{et al.}, Phys. Rev.B 90, 075125 (2014)] which allows to reduce the number of intermediate calculations required to reach convergence and to explicit estimate the error associated to the basis-set truncation.

Finite group lattice gauge theories for quantum simulation

The present manuscript focuses on Lattice Gauge Theories based on finite groups. For the purpose of Quantum Simulation, the Hamiltonian approach is considered, while the finite group serves as a discretization scheme for the degrees of freedom of the gauge fields. Several aspects of these models are studied. First, we investigate dualities in Abelian models with a restricted geometry, using a systematic approach. This leads to a rich phase diagram dependent on the super-selection sectors. Second, we construct a family of lattice Hamiltonians for gauge theories with a finite group, either Abelian or non-Abelian. We show that is possible to express the electric term as a natural graph Laplacian, and that the physical Hilbert space can be explicitly built using spin network states. In both cases we perform numerical simulations in order to establish the correctness of the theoretical results and further investigate the models.

Validação da Body Appreciation Scale (BAS), Life Satisfaction Index for the Third Age (LSITA) e do Aging Perception Questionnaire (APQ) para a língua portuguesa no Brasil : um estudo em idosos brasileiros

Universidade Estadual de Campinas . Faculdade de Educação Física