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Search Results: 1 - 10 of 15561 matches for " Anna Ludwicka-Bradley "
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Impact of Endothelial Microparticles on Coagulation, Inflammation, and Angiogenesis in Age-Related Vascular Diseases
Margaret Markiewicz,Erin Richard,Natalia Marks,Anna Ludwicka-Bradley
Journal of Aging Research , 2013, DOI: 10.1155/2013/734509
Abstract: Endothelial microparticles (EMPs) are complex vesicular structures that originate from plasma membranes of activated or apoptotic endothelial cells. EMPs play a significant role in vascular function by altering the processes of inflammation, coagulation, and angiogenesis, and they are key players in the pathogenesis of several vascular diseases. Circulating EMPs are increased in many age-related vascular diseases such as coronary artery disease, peripheral vascular disease, cerebral ischemia, and congestive heart failure. Their elevation in plasma has been considered as both a biomarker and bioactive effector of vascular damage and a target for vascular diseases. This review focuses on the pleiotropic roles of EMPs and the mechanisms that trigger their formation, particularly the involvement of decreased estrogen levels, thrombin, and PAI-1 as major factors that induce EMPs in age-related vascular diseases. 1. Introduction Vascular diseases are among the most common causes of morbidity and mortality, and both number and severity of morbid vascular conditions increase with age. Regulations of angiogenesis, coagulation, and inflammation are very important issues in vascular biology, both in normal physiology and pathology [1]. It is now well established that disruption of endothelial integrity represents a crucial event in the initiation and development of cardiovascular (CV) diseases. Numerous studies have reported that microparticles (MPs) play an important role in endothelial dysfunction. Endothelial dysfunction occurs when a perturbed homeostatic endothelium disrupts vascular competency resulting in reduced vasodilatation and increased proinflammatory and prothrombotic properties of the vascular network [2]. Recently, MPs originating from various cells have been found to be associated with several vascular related diseases. Moreover, exposed procoagulant phospholipids and specific receptors at the surface of MPs act as biomessengers linking inflammation, coagulation, and angiogenesis [3–5]. Although MPs were first described as “cellular debris” that are believed to have no biological significance, recent studies documented that MPs of endothelial and other origins are biological effectors in inflammation, vascular injury, angiogenesis, and thrombosis [6–8]. MPs isolated from granulation tissue are derived from endothelial cells, monocytes, platelets, erythrocytes [9–13], and myofibroblasts [8]. They exchange biological signals and information intercellularly and each kind of MP carries the antigens and receptors of the cells they originated. MPs may
Are Regional Habitat Models Useful at a Local-Scale? A Case Study of Threatened and Common Insectivorous Bats in South-Eastern Australia
Anna McConville, Bradley S. Law, Michael J. Mahony
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072420
Abstract: Habitat modelling and predictive mapping are important tools for conservation planning, particularly for lesser known species such as many insectivorous bats. However, the scale at which modelling is undertaken can affect the predictive accuracy and restrict the use of the model at different scales. We assessed the validity of existing regional-scale habitat models at a local-scale and contrasted the habitat use of two morphologically similar species with differing conservation status (Mormopterus norfolkensis and Mormopterus species 2). We used negative binomial generalised linear models created from indices of activity and environmental variables collected from systematic acoustic surveys. We found that habitat type (based on vegetation community) best explained activity of both species, which were more active in floodplain areas, with most foraging activity recorded in the freshwater wetland habitat type. The threatened M. norfolkensis avoided urban areas, which contrasts with M. species 2 which occurred frequently in urban bushland. We found that the broad habitat types predicted from local-scale models were generally consistent with those from regional-scale models. However, threshold-dependent accuracy measures indicated a poor fit and we advise caution be applied when using the regional models at a fine scale, particularly when the consequences of false negatives or positives are severe. Additionally, our study illustrates that habitat type classifications can be important predictors and we suggest they are more practical for conservation than complex combinations of raw variables, as they are easily communicated to land managers.
Comparison of Super Resolution Reconstruction Acquisition Geometries for Use in Mouse Phenotyping
Niranchana Manivannan,Bradley D. Clymer,Anna Bratasz,Kimerly A. Powell
International Journal of Biomedical Imaging , 2013, DOI: 10.1155/2013/820874
Abstract: 3D isotropic imaging at high spatial resolution (30–100 microns) is important for comparing mouse phenotypes. 3D imaging at high spatial resolutions is limited by long acquisition times and is not possible in many in vivo settings. Super resolution reconstruction (SRR) is a postprocessing technique that has been proposed to improve spatial resolution in the slice-select direction using multiple 2D multislice acquisitions. Any 2D multislice acquisition can be used for SRR. In this study, the effects of using three different low-resolution acquisition geometries (orthogonal, rotational, and shifted) on SRR images were evaluated and compared to a known standard. Iterative back projection was used for the reconstruction of all three acquisition geometries. The results of the study indicate that super resolution reconstructed images based on orthogonally acquired low-resolution images resulted in reconstructed images with higher SNR and CNR in less acquisition time than those based on rotational and shifted acquisition geometries. However, interpolation artifacts were observed in SRR images based on orthogonal acquisition geometry, particularly when the slice thickness was greater than six times the inplane voxel size. Reconstructions based on rotational geometry appeared smoother than those based on orthogonal geometry, but they required two times longer to acquire than the orthogonal LR images. 1. Introduction MRI is being used more frequently for evaluating morphological phenotypes in genetically engineered mouse models of disease [1]. 3D imaging at the highest spatial resolution is the preferred approach for comparing morphological phenotypes; however, it is not always possible in small animal in vivo imaging settings. This is due to the long acquisition times required to achieve high spatial resolution. Several-factors limit obtaining high-resolution 3D isotropic images in the in vivo settings such as the length of time a mouse can be kept under anesthesia, motion artifacts that are likely to occur during long acquisition protocols that degrade image quality, and increased repetition times required at the high magnetic field strengths used for small animal imaging. Keeping animals under anesthesia for long periods of time (>2?hrs) is not desirable. MRI acquisition protocols with very long repetition times ( ?ms), such as T2-weighted, diffusion-weighted (DW), and inversion recovery imaging are particularly affected by the long scan times required for 3D isotropic imaging. Thus, in vivo MR images in small animal studies are usually acquired using 2D
Is It Possible to Revitalize a Dying Language? An Examination of Attempts to Halt the Decline of Irish  [PDF]
Michael Bradley
Open Journal of Modern Linguistics (OJML) , 2014, DOI: 10.4236/ojml.2014.44047
Abstract: This paper evaluates the attempts to revitalize the indigenous language of Ireland. It examines how the number of native Irish speakers declined under British rule, and how this trend continued even after independence, when Irish was declared the country’s official language. Successive Irish governments have used two main strategies to reverse language shift. The first was to protect the small Irish speaking areas in the west of the country, the Gaeltacht. The second was to rely on schools elsewhere to produce new generations of fluent Irish speakers. By the 1970s it was apparent that neither policy was working. However since then, somewhat improbably, an increasing number of people have begun to use Irish, both inside and outside the Gaeltacht. This paper examines whether this revival constitutes reverse language shift. In particular, it asks to what extent Irish is now being passed on as a mother tongue to a new generation of children.
Risk of future trauma based on alcohol screening scores: A two-year prospective cohort study among US veterans
Alex H S Harris, Anna Lembke, Patricia Henderson, Shalini Gupta, Rudolf Moos, Katharine A Bradley
Addiction Science & Clinical Practice , 2012, DOI: 10.1186/1940-0640-7-6
Abstract: Outpatients (215, 924 male and 9168 female) who returned mailed AUDIT-C questionnaires were followed for 24 months in the medical record for any International Statistical Classification of Diseases and Related Health Problems (ICD-9) code related to trauma. The two-year prevalence of trauma was examined as a function of AUDIT-C scores, with low-level drinking (AUDIT-C 1-4) as the reference group. Men and women were examined separately, and age-stratified analyses were performed.Having an AUDIT-C score of 9-12 (indicating severe alcohol misuse) was associated with increased risk for trauma. Mean (SD) ages for men and women were 68.2 (11.5) and 57.2 (15.8), respectively. Age-stratified analyses showed that, for men [less than or equal to]50 years, those with AUDIT-C scores [greater than or equal to]9 had an increased risk for trauma compared with those with AUDIT-C scores in the 1-4 range (adjusted prevalence, 25.7% versus 20.8%, respectively; OR = 1.24; 95% confidence interval [CI], 1.03-1.50). For men [greater than or equal to]65 years with average comorbidity and education, those with AUDIT-C scores of 5-8 (adjusted prevalence, 7.9% versus 7.4%; OR = 1.16; 95% CI, 1.02-1.31) and 9-12 (adjusted prevalence 11.1% versus 7.4%; OR = 1.68; 95% CI, 1.30-2.17) were at significantly increased risk for trauma compared with men [greater than or equal to]65 years in the reference group. Higher AUDIT-C scores were not associated with increased risk of trauma among women.Men with severe alcohol misuse (AUDIT-C 9-12) demonstrate an increased risk of trauma. Men [greater than or equal to]65 showed an increased risk for trauma at all levels of alcohol misuse (AUDIT-C 5-8 and 9-12). These findings may be used as part of an evidence-based brief intervention for alcohol use disorders. More research is needed to understand the relationship between AUDIT-C scores and risk of trauma in women.
Pringsheim Convergence and the Dirichlet Function  [PDF]
Thomas Beatty, Bradley Hansen
Advances in Pure Mathematics (APM) , 2016, DOI: 10.4236/apm.2016.66031
Abstract: Double sequences have some unexpected properties which derive from the possibility of commuting limit operations. For example, \"\"may be defined so that the iterated limits \"\" and \"\"exist and are equal for all x, and yet the Pringsheim limit \"\" does not exist. The sequence \"\"is a classic example used to show that the iterated limit of a double sequence of continuous functions may exist, but result in an everywhere discontinuous limit. We explore whether the limit of this sequence in the Pringsheim sense equals the iterated result and derive an interesting property of cosines as a byproduct.
A brief community linkage intervention for veterans with a persistent mental illness and a co-occurring substance abuse disorder
Smelson,David A.; Losonczy,Miklos F.; Ziedonis,Douglas; Sussner,Bradley D.; Castles-Fonseca,Kathy; Rodrigues,Stephanie; Kline,Anna;
The European Journal of Psychiatry , 2007, DOI: 10.4321/S0213-61632007000200006
Abstract: objective: individuals with co-occurring psychiatric and substance abuse problems often exhibit poor outpatient treatment engagement and re-hospitalization following discharge from acute psychiatric services. although case management can improve treatment engagement and reduce attrition, these services are often delivered indefinitely, limiting the availability of treatment slots. in an effort to reduce re-hospitalization rates and improve outcomes during the transition from inpatient to outpatient treatment, we developed and evaluated time-limited case management (tlc), an eight-week integrated mental health and substance abuse augmentation intervention. method: sixty-five dually diagnosed veterans admitted to inpatient psychiatric treatment were included in the program evaluation, 32 who received the tlc service in addition to treatment as usual (tau) that began during inpatient treatment and continued after the transition to outpatient services, and a comparison group of 33 who received only tau without transitional support provided through the tlc augmentation service. results: the tlc group had fewer days and episodes of hospitalization at two and six month post-study entry. furthermore, the tlc group exhibited greater improvements on the global assessment of functioning from baseline to the six-month follow-up. conclusion: tlc appears to be an effective transitional augmentation service with benefits that persist beyond the eight weeks of the program. future research should include a larger and more rigorously controlled trial to confirm the efficacy and unique contributions of the intervention.
Synthesis and Characterization of Dual-Functionalized Core-Shell Fluorescent Microspheres for Bioconjugation and Cellular Delivery
Jonathan M. Behrendt, David Nagel, Evita Chundoo, Lois M. Alexander, Damien Dupin, Anna V. Hine, Mark Bradley, Andrew J. Sutherland
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0050713
Abstract: The efficient transport of micron-sized beads into cells, via a non-endocytosis mediated mechanism, has only recently been described. As such there is considerable scope for optimization and exploitation of this procedure to enable imaging and sensing applications to be realized. Herein, we report the design, synthesis and characterization of fluorescent microsphere-based cellular delivery agents that can also carry biological cargoes. These core-shell polymer microspheres possess two distinct chemical environments; the core is hydrophobic and can be labeled with fluorescent dye, to permit visual tracking of the microsphere during and after cellular delivery, whilst the outer shell renders the external surfaces of the microspheres hydrophilic, thus facilitating both bioconjugation and cellular compatibility. Cross-linked core particles were prepared in a dispersion polymerization reaction employing styrene, divinylbenzene and a thiol-functionalized co-monomer. These core particles were then shelled in a seeded emulsion polymerization reaction, employing styrene, divinylbenzene and methacrylic acid, to generate orthogonally functionalized core-shell microspheres which were internally labeled via the core thiol moieties through reaction with a thiol reactive dye (DY630-maleimide). Following internal labeling, bioconjugation of green fluorescent protein (GFP) to their carboxyl-functionalized surfaces was successfully accomplished using standard coupling protocols. The resultant dual-labeled microspheres were visualized by both of the fully resolvable fluorescence emissions of their cores (DY630) and shells (GFP). In vitro cellular uptake of these microspheres by HeLa cells was demonstrated conventionally by fluorescence-based flow cytometry, whilst MTT assays demonstrated that 92% of HeLa cells remained viable after uptake. Due to their size and surface functionalities, these far-red-labeled microspheres are ideal candidates for in vitro, cellular delivery of proteins.
Simplifying genetic disorders
David Bradley
Genome Biology , 2000, DOI: 10.1186/gb-spotlight-20001005-02
Abstract: In work published in the October issue of Nature Genetics, University of Chicago researchers have cleared a path to studying the genetic foundation of type 2, or non-insulin-dependent diabetes mellitus (NIDDM). In a study of a Mexican-American population and two white populations (Finns and Germans) they have found that small genetic variations, called single-nucleotide polymorphisms (SNPs), in a particular gene tend to occur more often in diabetics than in healthy relatives. Although finding a common genetic variation in family groups affected by simple genetic disorders is implicit, a gene implicated in a population with a complex disease could provide a potential new target for gene therapy. "Variation in this gene is associated with a threefold increased risk in the groups studied," explains lead researcher Graeme Bell.Bell and colleagues have used clever detective work coupled with brute force to positionally clone this gene, which seems to affect susceptibility to type 2 diabetes. They point the accusing finger at a gene encoding calpain-10, a ubiquitous cysteine protease, and demonstrate that specific combinations of polymorphisms in this gene are associated with disease risk. "These findings propose a fundamentally new hypothesis for diabetes research," says Leonid Kruglyak of the Fred Hutchison Cancer Center, Seattle, writing in an accompanying News and Views article. Superficially, the enzyme has no apparent connection with the disease but Bell's colleagues, led by Leslie Baier, have reported that variation in calpain-10 is associated with insulin resistance, so there are already clues as to a possible underlying mechanism.Some observers are cautious of proclaiming triumphs at this stage, suggesting that a new style genetics is needed to understand complex 21st century problems. "How well [Bell's results] will stand up to future tests and extrapolation remains to be seen," explains Kenneth Weiss of Penn State University. "We need to see if it is confirmed
Feedback on the FDA's February 2006 draft guidance on Patient Reported Outcome (PRO) measures from a developer of PRO measures
Clare Bradley
Health and Quality of Life Outcomes , 2006, DOI: 10.1186/1477-7525-4-78
Abstract: The US Department of Health and Human Services Food and Drug Administration (FDA) made public in February 2006 a document entitled 'Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims DRAFT GUIDANCE'. I have a particular interest in this draft guidance as I specialise in the design, development and use of PRO measures and license them for use in clinical trials, other research and routine clinical practice. My measures include:? the Diabetes Treatment Satisfaction Questionnaire (DTSQ) in its status (DTSQs) and change (DTSQc) forms [1-6] and related measures for other conditions including the HIVTSQ, RTSQ, RetTSQ, GHerpTSQ, ThyTSQ [7-12], and the newly designed DTSQ-Teen and DTSQ-Parent. The DTSQs and DTSQc are fully linguistically validated in 65 language versions? the Well-being Questionnaire (e.g. W-BQ12) [3,13-18] generic measure of well-being is psychometrically validated for a range of populations including those who have diabetes (type 1 and type 2) macular disease and growth hormone deficiency and fully linguistically validated in 37 language versions? the ADDQoL measure of the impact of diabetes on quality of life [4,19] with related measures for other conditions including RDQoL, RetDQoL, MacDQoL, HDQoL, A-RHDQoL, ThyDQoL, ADDQoL Teen [12,20-27] and recently designed ADDQoL Jnr (for 5–8 year olds) and ADDQoL Jnr+ (for 9–12 year olds). The ADDQoL, MacDQoL and RetDQoL are linguistically validated in 16–25 language versions.I welcome the FDA guidance as a much needed source of information about the standards required in PRO design, linguistic validation and psychometric validation. I recognise that the guidance may be very useful in encouraging good practice.I was one of the 56 individuals/organisations who submitted comments on the draft FDA guidelines by their deadline of 4th April. My original comments can be viewed with others on the FDA website [28]. I also attended a meeting in Washington
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