A myth exposed: Fast growth in diameter does not justify precocious abdominal aortic aneurysm repair

AbstractObjectives: fast growth of abdominal aortic aneurysm (AAA) diameter is claimed to be an indication for repair. We investigated the validity of this claim. Methods: between January 1988 and October 2000, 277 patients have had duplex sonography at six-monthly intervals in our aneurysm surveillance programme. During this period fast AAA growth was not an indication for operation in our unit. Results: we identified 63 patients whose aneurysms had grown 0.5 cm or more in 6 months. Thirty-one of the 63 patients had aneurysms measuring 5.5 cm or greater in anterior-posterior diameter after the fast growth and all have been operated on unless deemed not fit due to anaesthetic risk. The remaining 32 patients continued in surveillance for a total of 50 patient years and none had rupture of their aneurysm. The calculated 95% confidence interval for the risk of rupture was 0-6 per 100 patient years. Six patients, who would have been operated on if fast growth had been an indication, have been spared surgery of whom 3 died and 3 became unfit. Nine patients remained in surveillance at the end of the study. Conclusion: our data support the view that rapid increase in AAA diameter is not an indication for elective AAA repair.Eur J Vasc Endovasc Surg 25, 408-411 (2003

Biomarkers of coagulation and inflammation in dogs after randomized administration of 6% Hydroxyethyl Starch 130/0.4 or Hartmann’s Solution

Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES

Allergy, inflammation, hepatopathy and coagulation biomarkers in dogs with suspected anaphylaxis due to insect envenomation

Objectives: To compare concentrations of biomarkers of; allergy [mast cell tryptase (MCT) and histamine], inflammation [interleukin (IL)-6,-10, and−18, CXCL8, CCL2, keratinocyte chemoattractant (KC), C-reactive protein (CRP)], endothelial glycocalyx shedding (hyaluronan), coagulation [prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and von Willebrand Factor antigen, protein C (PC) and antithrombin (AT) activity], and hepatopathy [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin] between dogs with anaphylaxis after suspected insect exposure, dogs with critical illness, and healthy dogs. Design: This was a single center prospective clinical observational comparative biomarker study that included 25 dogs with anaphylaxis (evidence of insect exposure, acute dermatological signs, and other organ involvement), 30 dogs with other critical illness, and 20 healthy dogs. Differences across groups in biomarker concentrations were tested using one-way ANOVA or Kruskal-Wallis test, with significant P values (<0.05) reported for pairwise differences detected by post-hoc tests. Logistic regression models were used to calculate the area under the receiver operator characteristic curve (AUROC) for discrimination between anaphylaxis and non-anaphylactic illness. Results: Histamine concentration was significantly higher in the anaphylaxis group than the healthy (P < 0.001) and critically ill groups (P < 0.001), whereas no differences in MCT were detected amongst groups. Biomarker concentrations that were increased relative to healthy dogs in both the anaphylaxis and critically ill groups included IL-10 (P < 0.001 and P = 0.007, respectively), CCL2 (P = 0.007 and P < 0.001, respectively) and AST (both P < 0.001), whereas only the critically ill group had significantly increased CRP (P < 0.001), IL-6 (P < 0.001), KC (P < 0.001), ALP (P < 0.001), and fibrinogen (P = 0.016) concentrations, compared to the healthy group. Only dogs with anaphylaxis had significantly higher hyaluronan (P = 0.021) and ALT (P = 0.021) concentrations, and lower PC (P = 0.030) and AT (P = 0.032) activities, compared to healthy dogs. Both CRP and histamine concentration showed good discrimination between anaphylaxis and other critical illness, with an AUROC of 0.96 (95% CI 0.91–1) and 0.81 (95% CI 0.69–0.93), respectively. Conclusions: This preliminary study in dogs with anaphylaxis after suspected insect exposure, found evidence of an early innate immune response, glycocalyx shedding and anticoagulant consumption. Both CRP and histamine showed potential clinical utility for differentiation between anaphylaxis and other critical illness

Co-silencing of human Bub3 and dynein highlights an antagonistic relationship in regulating kinetochore-microtubule attachments

We previously reported that the spindle assembly checkpoint protein Bub3 is involved in regulating kinetochore-microtubule (KT-MT) attachments. Also, Bub3 was reported to interact with the microtubule motor protein dynein. Here we examined how this interaction contributes to KT-MT attachments. Depletion of Bub3 or dynein induced misaligned chromosomes, consistent with their role in KT-MT attachments. Unexpectedly, co-silencing of both proteins partially suppressed the misalignment phenotype and restored chromosome congression. Consistent with these observations, KT-MT attachments in co-depleted cells were stable, able to drive chromosome congression, and produce inter-and intra-kinetochore stretch, indicating they are functional. We suggest that a mutual antagonism exists between Bub3 and dynein to ensure optimal KT-MT attachments. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.CESPU [02-GCQF-CICS-2011N]; FCT - Fundacao para a Ciencia e a Tecnologia [CEQUIMED-PEst-OE/SAU/UI4040/2014]; FCT [SFRH/BD/90744/2012]info:eu-repo/semantics/publishedVersio

Enhanced cerebral blood volume under normobaric hyperoxia in the J20-hAPP mouse model of Alzheimer’s disease

Early impairments to neurovascular coupling have been proposed to be a key pathogenic factor in the onset and progression of Alzheimer’s disease (AD). Studies have shown impaired neurovascular function in several mouse models of AD, including the J20-hAPP mouse. In this study, we aimed to investigate early neurovascular changes using wild-type (WT) controls and J20-hAPP mice at 6 months of age, by measuring cerebral haemodynamics and neural activity to physiological sensory stimulations. A thinned cranial window was prepared to allow access to cortical vasculature and imaged using 2D-optical imaging spectroscopy (2D-OIS). After chronic imaging sessions where the skull was intact, a terminal acute imaging session was performed where an electrode was inserted into the brain to record simultaneous neural activity. We found that cerebral haemodynamic changes were significantly enhanced in J20-hAPP mice compared with controls in response to physiological stimulations, potentially due to the significantly higher neural activity (hyperexcitability) seen in the J20-hAPP mice. Thus, neurovascular coupling remained preserved under a chronic imaging preparation. Further, under hyperoxia, the baseline blood volume and saturation of all vascular compartments in the brains of J20-hAPP mice were substantially enhanced compared to WT controls, but this effect disappeared under normoxic conditions. This study highlights novel findings not previously seen in the J20-hAPP mouse model, and may point towards a potential therapeutic strategy

Effectiveness of Mouthguards for the Prevention of Orofacial Injuries and Concussions in Sports: Systematic Review and Meta-Analysis

Background: Sport activities can account for up to one-third of all orofacial injuries. Mouthguards (MGs) have been proposed as a way to reduce these injuries. Objectives: To present a systematic review and meta-analysis of the effectiveness of MGs for the prevention of sports-related orofacial injuries and concussions. Methods: Using specific search terms, PubMed, Ovid Embase, and the Cumulative Index to Nursing and Allied Health Literature were searched to find studies that (1) contained original quantitative data on MGs and orofacial injuries and/or concussions, (2) included groups involved in sports or exercise activities, (3) included MG users and non-MG users, and (4) provided either risk ratios (RRs) and 95% confidence intervals (95% CIs) comparing injuries among MG users and non-MG users, or data that could be used to calculate RRs and 95% CIs. Results: Twenty-six studies met the review criteria. Investigations employed a variety of study designs, utilized different types of MGs, used widely varying injury case definitions, and had multiple methodological weaknesses. Despite these limitations, meta-analyses indicated that the use of MGs reduced the overall risk of orofacial injuries in 12 cohort trials (summary RR [nonusers/users] = 2.33, 95% CI 1.59–3.44), and 11 trials involving self-report questionnaires (summary RR [nonusers/users] = 2.32, 95% CI 1.04–5.13). The influence of MGs on concussion incidence in five cohort studies was modest (summary RR [nonusers/users] = 1.25, 95% CI 0.90–1.74). Conclusion: These data indicate that MGs should be used in sports activities where there is significant orofacial injury risk

Equatorial circular orbits in the Kerr-de Sitter spacetimes

Equatorial motion of test particles in the Kerr-de Sitter spacetimes is considered. Circular orbits are determined, their properties are discussed for both the black-hole and naked-singularity spacetimes, and their relevance for thin accretion discs is established.Comment: 24 pages, 19 figures, REVTeX

SIMULATING AN ACCELERATION SCHEDULE FOR NDCX-II

The Virtual National Laboratory for Heavy-Ion Fusion Science is developing a physics design for NDCX-II, an experiment to study warm dense matter heated by ions. Present plans call for using 34 induction cells to accelerate 45 nC of Li+ ions to more than 3 MeV, followed by neutralized drift-compression. To heat targets to the desired temperatures, the beam must be compressed to a millimeter-scale radius and a duration of about 1 ns. A novel NDCX-II acceleration schedule has been developed using an interactive one-dimensional particle-in-cell simulation ASP to model the longitudinal physics and axisymmetric WARP simulations to validate the 1-D model and add transverse focusing. Three-dimensional Warp runs have been used recently to study the sensitivity to misalignments in the focusing solenoids

Standing-Wave Free-Electron Laser Two-Beam Accelerator

A free-electron laser (FEL) two-beam accelerator (TBA) is proposed, in which the FEL interaction takes place in a series of drive cavities, rather than in a waveguide. Each drive cavity is 'beat-coupled' to a section of the accelerating structure. This standing-wave TBA is investigated theoretically and numerically, with analyses included of microwave extraction, growth of the FEL signal through saturation, equilibrium longitudinal beam dynamics following saturation, and sensitivity of the microwave amplitude and phase to errors in current and energy. It is found that phase errors due to current jitter are substantially reduced from previous versions of the TBA. Analytic scalings and numerical simulations are used to obtain an illustrative TBA parameter set