11,765 research outputs found
Riemannian Walk for Incremental Learning: Understanding Forgetting and Intransigence
Incremental learning (IL) has received a lot of attention recently, however,
the literature lacks a precise problem definition, proper evaluation settings,
and metrics tailored specifically for the IL problem. One of the main
objectives of this work is to fill these gaps so as to provide a common ground
for better understanding of IL. The main challenge for an IL algorithm is to
update the classifier whilst preserving existing knowledge. We observe that, in
addition to forgetting, a known issue while preserving knowledge, IL also
suffers from a problem we call intransigence, inability of a model to update
its knowledge. We introduce two metrics to quantify forgetting and
intransigence that allow us to understand, analyse, and gain better insights
into the behaviour of IL algorithms. We present RWalk, a generalization of
EWC++ (our efficient version of EWC [Kirkpatrick2016EWC]) and Path Integral
[Zenke2017Continual] with a theoretically grounded KL-divergence based
perspective. We provide a thorough analysis of various IL algorithms on MNIST
and CIFAR-100 datasets. In these experiments, RWalk obtains superior results in
terms of accuracy, and also provides a better trade-off between forgetting and
intransigence
Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host
BACKGROUND: The ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time. RESULTS: SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS. CONCLUSION: Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission
Outcomes linked to eligibility for stem cell transplantation trials in diffuse cutaneous systemic sclerosis
Objectives:
The aim of this study was to explore outcomes in a cohort of diffuse cutaneous systemic sclerosis (dcSSc) patients fulfilling eligibility criteria for stem cell transplantation (SCT) studies but receiving standard immunosuppression.
Methods:
From a large single-centre dcSSc cohort (n = 636), patients were identified using the published SCT trials’ inclusion criteria. Patients meeting the trials’ exclusion criteria were excluded.
Results:
Of the 227 eligible patients, 214 met the inclusion criteria for ASTIS, 82 for SCOT and 185 for the UPSIDE trial, and 66 were excluded based on age > 65 years, low DLco, pulmonary hypertension or creatinine clearance <40ml/min. The mean follow-up time was 12 years (SD 7). Among the eligible patients, 103 (45.4%) died. Survival was 96% at 2-, 88% at 5-, 73% at 10- and 43% at 20 years. Compared with this ‘SCT-eligible’ cohort, those patients who would have been excluded from SCT trials had a worse long-term survival (97% at 2-, 77% at 5-, 52% at 10- and 15% at 20 years, log rank p< 0.001). Excluded patients also had a significantly worse long-term event free survival. Hazard of death was higher in patients with higher age at onset (HR 1.05, p< 0.001), higher ESR at baseline (HR 1.01, p= 0.025) and males (HR 2.12, p= 0.008).
Conclusion:
SCT inclusion criteria identify patients with poor outcome despite current best practice treatment. Patients meeting the inclusion criteria for SCT but who would have been excluded from the trials because of age, pulmonary hypertension, poor kidney function or DLco <40%, had worse outcomes
Second Order Asymptotic Boundary Conditions for Modeling of Imperfect Interface
The interface between two solids has properties differing from those of the bulk media. The actual structure of such an interface depends on the particular type of solid contact: contact formed during solidification, metallurgical solid bond, dry mechanical or lubricated contact, et cetera. The classical boundary conditions which are satisfied for an infinitely thin perfect bond are not adequate to describe wave interaction with such an imperfect interface.</p
The epiphyseal scar: changing perceptions in relation to skeletal age estimation.
BACKGROUND: It is imperative that all methods applied in skeletal age estimation and the criteria on which they are based have a strong evidential basis. The relationship between the persistence of epiphyseal scars and chronological age, however, has remained largely untested. AIMS: To assess the relationships between the level of persistence of the epiphyseal scar and chronological age, biological sex and side of the body in relation to the interpretation of epiphyseal scars in methods of skeletal age estimation. SUBJECTS AND METHODS: A sample of radiographic images was obtained from the Tayside NHS Trust, Ninewells Hospital, Dundee, UK. This included images of four anatomical regions from living female and male individuals aged between 20-50 years. RESULTS: Some remnant of an epiphyseal scar was found in 78-99% of individuals examined in this study. The level of persistence of epiphyseal scars was also found to vary between anatomical regions. CONCLUSION: The overall relationship between chronological age and the level of persistence or obliteration of the epiphyseal scar was found to be of insufficient strength to support a causative link. It is, therefore, necessary that caution is employed in their interpretation in relation to skeletal age estimation practices
The molecular dimension of microbial species: 1. Ecological distinctions among, and homogeneity within, putative ecotypes of Synechococcus inhabiting the cyanobacterial mat of Mushroom Spring, Yellowstone National Park
© 2015 Becraft, Wood, Rusch, Kühl, Jensen, Bryant, Roberts, Cohan and Ward. Based on the Stable Ecotype Model, evolution leads to the divergence of ecologically distinct populations (e.g., with different niches and/or behaviors) of ecologically interchangeable membership. In this study, pyrosequencing was used to provide deep sequence coverage of Synechococcus psaA genes and transcripts over a large number of habitat types in the Mushroom Spring microbial mat. Putative ecological species (putative ecotypes), which were predicted by an evolutionary simulation based on the Stable Ecotype Model (Ecotype Simulation), exhibited distinct distributions relative to temperature-defined positions in the effluent channel and vertical position in the upper 1 mm-thick mat layer. Importantly, in most cases variants predicted to belong to the same putative ecotype formed unique clusters relative to temperature and depth in the mat in canonical correspondence analysis, supporting the hypothesis that while the putative ecotypes are ecologically distinct, the members of each ecotype are ecologically homogeneous. Putative ecotypes responded differently to experimental perturbations of temperature and light, but the genetic variation within each putative ecotype was maintained as the relative abundances of putative ecotypes changed, further indicating that each population responded as a set of ecologically interchangeable individuals. Compared to putative ecotypes that predominate deeper within the mat photic zone, the timing of transcript abundances for selected genes differed for putative ecotypes that predominate in microenvironments closer to upper surface of the mat with spatiotemporal differences in light and O2 concentration. All of these findings are consistent with the hypotheses that Synechococcus species in hot spring mats are sets of ecologically interchangeable individuals that are differently adapted, that these adaptations control their distributions, and that the resulting distributions constrain the activities of the species in space and time
Global well-posedness of the Kirchhoff equation and Kirchhoff systems
This article is devoted to review the known results on global well-posedness
for the Cauchy problem to the Kirchhoff equation and Kirchhoff systems with
small data. Similar results will be obtained for the initial-boundary value
problems in exterior domains with compact boundary. Also, the known results on
large data problems will be reviewed together with open problems.Comment: arXiv admin note: text overlap with arXiv:1211.300
On stability of discretizations of the Helmholtz equation (extended version)
We review the stability properties of several discretizations of the
Helmholtz equation at large wavenumbers. For a model problem in a polygon, a
complete -explicit stability (including -explicit stability of the
continuous problem) and convergence theory for high order finite element
methods is developed. In particular, quasi-optimality is shown for a fixed
number of degrees of freedom per wavelength if the mesh size and the
approximation order are selected such that is sufficiently small and
, and, additionally, appropriate mesh refinement is used near
the vertices. We also review the stability properties of two classes of
numerical schemes that use piecewise solutions of the homogeneous Helmholtz
equation, namely, Least Squares methods and Discontinuous Galerkin (DG)
methods. The latter includes the Ultra Weak Variational Formulation
The impact of a medication review with follow-up service on hospital admissions in aged polypharmacy patients
© 2016 The British Pharmacological Society Aims: The aims were to assess the impact of a medication review with follow-up (MRF) service provided in community pharmacy to aged polypharmacy patients on the number of medication-related hospital admissions and to estimate the effect on hospital costs. Methods: This was a sub-analysis of a cluster randomized controlled trials carried out in 178 community pharmacies in Spain. Pharmacies in the intervention group (IG) provided a comprehensive medication review during 6 months. Pharmacists in the comparison group (CG) delivered usual care. For the purposes of this sub-analysis, an expert panel of three internal medicine specialists screened the hospitalizations occurring during the main study, in order to identify medication-related hospitalizations. Inter-rater reliability was measured using Fleiss's kappa. Hospital costs were calculated using diagnosis related groups. Results: One thousand four hundred and three patients were included in the main study and they had 83 hospitalizations. Forty-two hospitalizations (50.6%) were medicine-related, with a substantial level of agreement among the experts (kappa = 0.65, 95% CI 0.52, 0.78, P < 0.01). The number of medication-related hospitalizations was significantly lower in patients receiving MRF (IG 11, GC 31, P = 0.042). The probability of being hospitalized was 3.7 times higher in the CG (odds ratio 3.7, 95% CI 1.2, 11.3, P = 0.021). Costs for a medicine-related hospitalization were €6672. Medication-related hospitalization costs were lower for patients receiving MRF [IG: €94 (SD 917); CG: €301 (SD 2102); 95% CI 35.9, 378.0, P = 0.018]. Conclusion: MRF provided by community pharmacists might be an effective strategy to balance the assurance of the benefit from medications and the avoidance of medication-related hospitalizations in aged patients using polypharmacy
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