1,451 research outputs found
Finite Element Methods for Elliptic Distributed Optimal Control Problems with Pointwise State Constraints
Finite element methods for a model elliptic distributed optimal control
problem with pointwise state constraints are considered from the perspective of
fourth order boundary value problems
Impact of Indirect Contacts in Emerging Infectious Disease on Social Networks
Interaction patterns among individuals play vital roles in spreading
infectious diseases. Understanding these patterns and integrating their impact
in modeling diffusion dynamics of infectious diseases are important for
epidemiological studies. Current network-based diffusion models assume that
diseases transmit through interactions where both infected and susceptible
individuals are co-located at the same time. However, there are several
infectious diseases that can transmit when a susceptible individual visits a
location after an infected individual has left. Recently, we introduced a
diffusion model called same place different time (SPDT) transmission to capture
the indirect transmissions that happen when an infected individual leaves
before a susceptible individual's arrival along with direct transmissions. In
this paper, we demonstrate how these indirect transmission links significantly
enhance the emergence of infectious diseases simulating airborne disease
spreading on a synthetic social contact network. We denote individuals having
indirect links but no direct links during their infectious periods as hidden
spreaders. Our simulation shows that indirect links play similar roles of
direct links and a single hidden spreader can cause large outbreak in the SPDT
model which causes no infection in the current model based on direct link. Our
work opens new direction in modeling infectious diseases.Comment: Workshop on Big Data Analytics for Social Computing,201
Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity
Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever
CT pulmonary angiography: an over-utilized imaging modality in hospitalized patients with suspected pulmonary embolism
Aims: To determine if computed tomographic pulmonary angiography (CTPA) was overemployed in the evaluation of hospitalized patients with suspected acute pulmonary embolism (PE). Methods: Data were gathered retrospectively on hospitalized patients (n=185) who had CTPA for suspected PE between June and August 2009 at our institution. Results: CTPA was done in 185 hospitalized patients to diagnose acute PE based on clinical suspicion. Of these, 30 (16.2%) patients were tested positive for acute PE on CTPA. The Well's pretest probability for PE was low, moderate, and high in 77 (41.6%), 83 (44.9%), and 25 (13.5%) patients, respectively. Out of the 30 PE-positive patients, pretest probability was low in 2 (6.6%), moderate in 20 (66.7%), and high in 8 (26.6%) (p=0.003). Modified Well's criteria applied to all patients in our study revealed 113 (61%) with low and 72 (39%) with high clinical pretest probability. When modified Well's criteria was applied to 30 PE-positive patients, 10 (33.3%) and 20 (66.6%) were found to have low and high pretest probability, respectively (p=0.006). D-dimer assay was done in 30 (16.2%) of the inpatients with suspected PE and all of them were found to have elevated levels. A lower extremity duplex ultrasound confirmed deep venous thrombosis in 17 (9.1%) of the patients with suspected PE, at least 1 week prior to having CTPA. Conclusion: Understanding the recommended guidelines, evidence-based literature, and current concepts in evaluation of patients with suspected acute PE will reduce unnecessary CTPA examinations
Inflammasome and IL-1β-Mediated Disorders
The NLRP3 inflammasome is an intracellular complex that regulates the release of proinflammatory cytokines such as interleukin-1β in response to exogenous pathogens and endogenous danger signals. Evidence from studies involving human genetics, human ex vivo mononuclear cell responses, and in vivo and in vitro murine models confirms the importance of the inflammasome and interleukin-1β in the pathogenesis of several inherited and complex diseases. The availability of several effective interleukin-1β targeted therapies has allowed for successful proof-of-concept studies in several of these disorders. However, many other diseases are likely to be mediated by the inflammasome and interleukin-1β, providing additional targets in the future
A nearly continuous measure of birth weight for gestational age using a United States national reference
BACKGROUND: Fully understanding the determinants and sequelae of fetal growth requires a continuous measure of birth weight adjusted for gestational age. Published United States reference data, however, provide estimates only of the median and lowest and highest 5(th )and 10(th )percentiles for birth weight at each gestational age. The purpose of our analysis was to create more continuous reference measures of birth weight for gestational age for use in epidemiologic analyses. METHODS: We used data from the most recent nationwide United States Natality datasets to generate multiple reference percentiles of birth weight at each completed week of gestation from 22 through 44 weeks. Gestational age was determined from last menstrual period. We analyzed data from 6,690,717 singleton infants with recorded birth weight and sex born to United States resident mothers in 1999 and 2000. RESULTS: Birth weight rose with greater gestational age, with increasing slopes during the third trimester and a leveling off beyond 40 weeks. Boys had higher birth weights than girls, later born children higher weights than firstborns, and infants born to non-Hispanic white mothers higher birth weights than those born to non-Hispanic black mothers. These results correspond well with previously published estimates reporting limited percentiles. CONCLUSIONS: Our method provides comprehensive reference values of birth weight at 22 through 44 completed weeks of gestation, derived from broadly based nationwide data. Other approaches require assumptions of normality or of a functional relationship between gestational age and birth weight, which may not be appropriate. These data should prove useful for researchers investigating the predictors and outcomes of altered fetal growth
Domain analysis of lipoprotein LppQ in Mycoplasma mycoides subsp. mycoides SC
The lipoprotein LppQ is the most prominent antigen of Mycoplasma mycoides subsp. mycoides small colony type (SC) during infection of cattle. This pathogen causes contagious bovine pleuropneumonia (CBPP), a devastating disease of considerable socio-economic importance in many countries worldwide. The dominant antigenicity and high specificity for M. mycoides subsp. mycoides SC of lipoprotein LppQ have been exploited for serological diagnosis and for epidemiological investigations of CBPP. Scanning electron microscopy and immunogold labelling were used to provide ultrastructural evidence that LppQ is located to the cell membrane at the outer surface of M. mycoides subsp. mycoides SC. The selectivity and specificity of this method were demonstrated through discriminating localization of extracellular (i.e., in the zone of contact with host cells) vs. integral membrane domains of LppQ. Thus, our findings support the suggestion that the accessible N-terminal domain of LppQ is surface exposed and such surface localization may be implicated in the pathogenesis of CBPP
Unintentional injuries in children with disabilities:a systematic review and meta-analysis
Children with disabilities are thought to have an increased risk of unintentional injuries, but quantitative syntheses of findings from previous studies have not been done. We conducted a systematic review and meta-analysis to assess whether pre-existing disability can increase the risk of unintentional injuries among children when they are compared to children without disability. We searched 13 electronic databases to identify original research published between 1 January 1990 and 28 February 2013. We included those studies that reported on unintentional injuries among children with pre-existing disabilities compared with children without disabilities. We conducted quality assessments and then calculated pooled odds ratios of injury using random-effects models. Fifteen eligible studies were included from 24,898 references initially identified, and there was a total sample of 83,286 children with disabilities drawn from the eligible studies. When compared with children without disabilities, the pooled OR of injury was 1.86 (95 % CI 1.65-2.10) in children with disabilities. The pooled ORs of injury were 1.28, 1.75, and 1.86 in the 0-4 years, 5-9 years, and ≥10 years of age subgroups, respectively. Compared with children without disabilities, the pooled OR was 1.75 (95 % CI 1.26-2.43) among those with International Classification of Functioning (ICF) limitations. When disability was defined as physical disabilities, the pooled OR was 2.39 (95 % CI 1.43-4.00), and among those with cognitive disabilities, the pooled OR was 1.77 (95 % CI 1.49-2.11). There was significant heterogeneity in the included studies. Compared with peers without disabilities, children with disabilities are at a significantly higher risk of injury. Teens with disabilities may be an important subgroup for future injury prevention efforts. More data are needed from low- and middle-income countries
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