The Initial Configuration of Young Stellar Clusters: A K-band Number Counts Analysis of the Surface Density of Stars

We present an analysis of K-band stellar distributions for the young stellar clusters GGD 12-15, IRAS 20050+2720, and NGC 7129. We find that the two deeply embedded clusters, GGD 12-15 and IRAS 20050+2720, are not azimuthally symmetric and show a high degree of structure which traces filamentary structure observed in 850 micron emission maps. In contrast, the NGC 7129 cluster is circularly symmetric, less dense, and anti-correlated to 850 micron emission, suggesting recent gas expulsion and dynamical expansion have occured. We estimate stellar volume densities from nearest neighbor distances, and discuss the impact of these densities on the evolution of circumstellar disks and protostellar envelopes in these regions.Comment: 44 pages, 26 figures, Accepted to ApJ. Changes include extinction mapping, Monte Carlo field star modeling, and Nyquist sampled azimuthal stellar distributions. A version with full resolution figures is available at http://astro.pas.rochester.edu/~rguter/preprints/gutermuth_sd.tar.g

Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues

Introduction: The small leucine-rich proteoglycans (SLRPs) modulate tissue organization, cellular proliferation, matrix adhesion, growth factor and cytokine responses, and sterically protect the surface of collagen type I and II fibrils from proteolysis. Catabolism of SLRPs has important consequences for the integrity of articular cartilage and meniscus by interfering with their tissue homeostatic functions. Methods: SLRPs were dissociatively extracted from articular cartilage from total knee and hip replacements, menisci from total knee replacements, macroscopically normal and fibrillated knee articular cartilage from mature age-matched donors, and normal young articular cartilage. The tissue extracts were digested with chondroitinase ABC and keratanase-I before identification of SLRP core protein species by Western blotting using antibodies to the carboxyl-termini of the SLRPs. Results: Multiple core-protein species were detected for all of the SLRPs (except fibromodulin) in the degenerate osteoarthritic articular cartilage and menisci. Fibromodulin had markedly less fragments detected with the carboxyl-terminal antibody compared with other SLRPs. There were fewer SLRP catabolites in osteoarthritic hip than in knee articular cartilage. Fragmentation of all SLRPs in normal age-matched, nonfibrillated knee articular cartilage was less than in fibrillated articular cartilage from the same knee joint or total knee replacement articular cartilage specimens of similar age. There was little fragmentation of SLRPs in normal control knee articular cartilage. Only decorin exhibited a consistent increase in fragmentation in menisci in association with osteoarthritis. There were no fragments of decorin, biglycan, lumican, or keratocan that were unique to any tissue. A single fibromodulin fragment was detected in osteoarthritic articular cartilage but not meniscus. All SLRPs showed a modest age-related increase in fragmentation in knee articular and meniscal cartilage but not in other tissues. Conclusion: Enhanced fragmentation of SLRPs is evident in degenerate articular cartilage and meniscus. Specific decorin and fibromodulin core protein fragments in degenerate meniscus and/or human articular cartilage may be of value as biomarkers of disease. Once the enzymes responsible for their generation have been identified, further research may identify them as therapeutic targets

Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia

The disease known as late-onset Alzheimer\u27s disease is a neurodegenerative condition recognized as the single most common form of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary tangles, neuropil threads, neuritic senile plaques and often deposits of amyloid around the cerebrovasculature. Although many studies have provided a relatively detailed knowledge of these putatively pathogenic entities, understanding of the events that initiate and support the biological processes generating them and the subsequent observable neuropathology and neurodegeneration remain limited. This is especially true in the case of late-onset disease. Although early-onset Alzheimer\u27s disease has been shown conclusively to have genetic roots, the detailed etiologic initiation of late-onset disease without such genetic origins has remained elusive. Over the last 15 years, current and ongoing work has implicated infection in the etiology and pathogenesis of late-onset dementia. Infectious agents reported to be associated with disease initiation are various, including several viruses and pathogenic bacterial species. We have reported extensively regarding an association between late-onset disease and infection with the intracellular bacterial pathoge

Treatment compliance and effectiveness of a cognitive behavioural intervention for low back pain : a complier average causal effect approach to the BeST data set

Background: Group cognitive behavioural intervention (CBI) is effective in reducing low-back pain and disability in comparison to advice in primary care. The aim of this analysis was to investigate the impact of compliance on estimates of treatment effect and to identify factors associated with compliance. Methods: In this multicentre trial, 701 adults with troublesome sub-acute or chronic low-back pain were recruited from 56 general practices. Participants were randomised to advice (control n = 233) or advice plus CBI (n = 468). Compliance was specified a priori as attending a minimum of three group sessions and the individual assessment. We estimated the complier average causal effect (CACE) of treatment. Results: Comparison of the CACE estimate of the mean treatment difference to the intention-to-treat (ITT) estimate at 12 months showed a greater benefit of CBI amongst participants compliant with treatment on the Roland Morris Questionnaire (CACE: 1.6 points, 95% CI 0.51 to 2.74; ITT: 1.3 points, 95% CI 0.55 to 2.07), the Modified Von Korff disability score (CACE: 12.1 points, 95% CI 6.07 to 18.17; ITT: 8.6 points, 95% CI 4.58 to 12.64) and the Modified von Korff pain score (CACE: 10.4 points, 95% CI 4.64 to 16.10; ITT: 7.0 points, 95% CI 3.26 to 10.74). People who were non-compliant were younger and had higher pain scores at randomisation. Conclusions: Treatment compliance is important in the effectiveness of group CBI. Younger people and those with more pain are at greater risk of non-compliance

Factors associated with Anaplasma spp. seroprevalence among dogs in the United States

Background Dogs in the United States are hosts to a diverse range of ticks and tick-borne pathogens, including A. phagocytophilum, an important emerging canine and human pathogen. Previously, a Companion Animal Parasite Council (CAPC)-sponsored workshop proposed factors purported to be associated with the infection risk for tick-transmitted pathogens in dogs in the United States, including climate conditions, socioeconomic characteristics, local topography, and vector distribution. Methods Approximately four million test results from routine veterinary diagnostic tests from 2011–2013, which were collected on a county level across the contiguous United States, are statistically analyzed with the proposed factors via logistic regression and generalized estimating equations. Spatial prevalence maps of baseline Anaplasma spp. prevalence are constructed from Kriging and head-banging smoothing methods. Results All of the examined factors, with the exception of surface water coverage, were significantly associated with Anaplasma spp. prevalence. Overall, Anaplasma spp. prevalence increases with increasing precipitation and forestation coverage and decreases with increasing temperature, population density, relative humidity, and elevation. Interestingly, socioeconomic status and deer/vehicle collisions were positively and negatively correlated with canine Anaplasma seroprevalence, respectively. A spatial map of the canine Anaplasma hazard is an auxiliary product of the analysis. Anaplasma spp. prevalence is highest in New England and the Upper Midwest. Conclusions The results from the two posited statistical models (one that contains an endemic areas assumption and one that does not) are in general agreement, with the major difference being that the endemic areas model estimates a larger prevalence in Western Texas, New Mexico, and Colorado. As A. phagocytophilum is zoonotic, the results of this analysis could also help predict areas of high risk for human exposure to this pathogen

Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review

Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability.

Factor XIII (FXIII) is an important proenzyme in the hemostatic system. The plasma-derived enzyme activated FXIII cross-links fibrin fibers within thrombi to increase their mechanical strength and cross-links fibrin to fibrinolytic inhibitors, specifically α2-antiplasmin, to increase resistance to fibrinolysis. We have previously shown that cellular FXIII (factor XIII-A [FXIII-A]), which is abundant in the platelet cytoplasm, is externalized onto the activated membrane and cross-links extracellular substrates. The contribution of cellular FXIII-A to platelet activation and platelet function has not been extensively studied. This study aims to identify the role of platelet FXIII-A in platelet function. We used normal healthy platelets with a cell permeable FXIII inhibitor and platelets from FXIII-deficient patients as a FXIII-free platelet model in a range of platelet function and clotting tests. Our data demonstrate that platelet FXIII-A enhances fibrinogen binding to the platelet surface upon agonist stimulation and improves the binding of platelets to fibrinogen and aggregation under flow in a whole-blood thrombus formation assay. In the absence of FXIII-A, platelets show reduced sensitivity to agonist stimulation, including decreased P-selectin exposure and fibrinogen binding. We show that FXIII-A is involved in platelet spreading where a lack of FXIII-A reduces the ability of platelets to fully spread on fibrinogen and collagen. Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent. Overall, this study shows that platelet FXIII-A functions during thrombus formation by aiding platelet activation and thrombus retraction in addition to its antifibrinolytic roles