Carotid atherosclerotic plaque rupture and its sequelae are among the leading causes of acute ischemic stroke. The risk of rupture and subsequent thrombosis is, among others, determined by vulnerable ...plaque characteristics and linked to activation of the immune system, in which neutrophil extracellular traps (NETs) potentially play a role. The aim of this study was to investigate how plaque vulnerability is associated with NETs levels. We included 182 patients from the Plaque At RISK (PARISK) study in whom carotid imaging was performed to measure plaque ulceration, fibrous cap integrity, intraplaque hemorrhage, lipid-rich necrotic core, calcifications and plaque volume. Principal component analysis generated a 'vulnerability index' comprising all plaque characteristics. Levels of the NETs marker myeloperoxidase-DNA complex were measured in patient plasma. The association between the vulnerability index and low or high NETs levels (dependent variable) was assessed by logistic regression. No significant association between the vulnerability index and NETs levels was detected in the total population (odds ratio 1.28, 95% confidence interval 0.90-1.83, p = 0.18). However, in the subgroup of patients naive to statins or antithrombotic medication prior to the index event, this association was statistically significant (odds ratio 2.08, 95% confidence interval 1.04-4.17, p = 0.04). Further analyses revealed that this positive association was mainly driven by intraplaque hemorrhage, lipid-rich necrotic core and ulceration. In conclusion, plaque vulnerability is positively associated with plasma levels of NETs, but only in patients naive to statins or antithrombotic medication prior to the index event.
The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools.
Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of ...pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone.
Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.
Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque ...calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58-0.90 respectively OR = 2.24, 95% CI 1.60-3.13).We found significant correlation for change in ECAC volume with diabetes (β = 0.46, 95% CI 0.03-0.89) and baseline ECAC volume (β = 0.81, 95% CI 0.73-0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48-3.16), age (OR = 2.00, 95% CI 1.19-3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20-11.96).The overall change of ICAC volume was also significantly correlated with diabetes (β = 0.92, 95% CI 1.59-7.02), use of oral hypoglycemic drugs (β = 0.86, 95% CI 0.12-1.59) and baseline ICAC volume (β = 0.71, 95% CI 0.55-0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.
Simulations of effusion from ISOL target/ion source systems Mustapha, B; Nolen, J.A
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
03/2004, Letnik:
521, Številka:
1
Journal Article
Recenzirano
Monte Carlo simulations of the low- and high-conductivity Target/Ion Source systems used at Oak Ridge National Laboratory for effusion measurements are performed. Comparisons with the corresponding ...experimental data for the different geometries are presented and discussed. Independent checks of the simulation using data for simple geometries and using the conductance approach well known in vacuum technology are performed. A simulation-based comparison between the low- and high-conductivity systems is also presented.
Evolving new technologies in vascular access mandate increased attention to patient safety; an often overlooked yet valuable training tool is simulation. For the end-stage renal disease patient, ...simulation tools are effective for all aspects of creating access for peritoneal dialysis and hemodialysis. Based on aviation principles, known as crew resource management, we place equal emphasis on team training as individual training to improve interactions between team members and systems, cumulating in improved safety. Simulation allows for environmental control and standardized procedures, letting the trainee practice and correct mistakes without harm to patients, compared with traditional patient-based training. Vascular access simulators range from suture devices, to pressurized tunneled conduits for needle cannulation, to computer-based interventional simulators. Simulation training includes simulated case learning, root cause analysis of adverse outcomes, and continual update and refinement of concepts. Implementation of effective human to complex systems interaction in end-stage renal disease patients involves a change in institutional culture. Three concepts discussed in this article are as follows: (1) the need for user-friendly systems and technology to enhance performance, (2) the necessity for members to both train and work together as a team, and (3) the team assigned to use the system must test and practice it to a proficient level before safely using the system on patients.
Renal transplant patients sensitized to HLA antigens comprise nearly one‐third of the UNOS wait‐list and receive 14% of deceased donor (DD) transplants, a rate half that of unsensitized patients. ...Between 1999 and 2003, we performed 492 adult renal transplants from DD; 120 patients (∼25%) had a panel reactive antibody (PRA) of >30%, with nearly half (n = 58) having a PRA of >80%. Our approach is based upon high‐resolution solid‐phase HLA antibody analysis to identify class I/II antibodies and a ‘virtual crossmatch’ to predict compatible donor/recipient combinations. Recipients are excluded from the United Network for Organ Sharing match run if donors possess unacceptable antigens. Thus, when sensitized patients appear on the match run, they have a high probability of a negative final crossmatch. Here, we describe our 5‐year experience with this approach. Five‐year graft survival ranged from 66% to 70% among unsensitized (n = 272), moderately sensitized (PRA < 30%, n = 100) and highly sensitized (>30% PRA; n = 120) patients, equal to the average national graft survival (65.7%). The application of this approach (the Emory Algorithm) provides a logical and systematic approach to improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients awaiting renal transplantation.
The authors describe an algorithm for transplanting highly‐sensitized kidney patients based on high resolution HLA antibody analysis and a virtual crossmatch to predict compatibility and a high probability of negativity in the actual final crossmatch. See also editorial by B Hippen in this issue on page 2230.
The Super-FRS project at GSI Geissel, H.; Weick, H.; Winkler, M. ...
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms,
05/2003, Letnik:
204
Journal Article, Conference Proceeding
Recenzirano
The GSI projectile fragment separator FRS has demonstrated with many pioneering experiments the research potential of in-flight separators at relativistic energies. Although the present facility has ...contributed much to the progress in the field of nuclear structure physics, major improvements are desirable in the future. The characteristics of the proposed next-generation facility at GSI, the Super-FRS, will be presented and compared to other projects. The Super-FRS is a large-acceptance superconducting fragment separator followed by different experimental branches including a combination with a new storage-cooler ring system. This system consists of a collector ring (CR) and a new experimental storage ring (NESR) which allow precision mass and lifetime measurements as well as in-ring reaction studies. The NESR can be operated in combination with an electron ring to measure electron scattering with exotic nuclei. This electron heavy-ion collider will open up new fields for nuclear structure research.
Highlights • A subtle, partial T cell deficiency has been found in bipolar offspring over time. • T cell subsets followed a dynamic course from adolescence into adulthood. • During adolescence, a ...high inflammatory state was detected in bipolar offspring. • T cell aberrancies do not directly predict mood disorder development.
Background: We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and thyroid failure in outpatients with bipolar disorder compared with two control groups.
Methods: The TPO-Abs of ...outpatients with DSM-IV bipolar disorder (n = 226), a population control group (n = 252), and psychiatric inpatients of any diagnosis (n = 3190) were measured. Thyroid failure was defined as a raised thyroid stimulating hormone level, previously diagnosed hypothyroidism, or both. Subjects were compared with attention to age, gender, and exposure to lithium.
Results: The TPO-Abs were more prevalent in bipolar patients (28%) than population and psychiatric controls (3–18%). The presence of TPO-Abs in bipolar patients was associated with thyroid failure, but not with age, gender, mood state, rapid cycling, or lithium exposure. Thyroid failure was present in 17% of bipolar patients and more prevalent in women. It was associated with lithium exposure, especially in the presence of TPO-Abs, but not with current rapid cycling, although an association may have been masked by thyroid hormone replacement.
Conclusions: Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment. These variables appear to be independent risk factors for the development of hypothyroidism, especially in women with bipolar disorder.
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