Exercise capacity and biventricular function in adult patients with repaired tetralogy of Fallot

BACKGROUND: Adult patients with repaired tetralogy of Fallot (rTOF) often have diminished exercise capacity. The primary objective of this study was to examine whether abnormalities of biventricular function play a role in exercise limitation in patients with rTOF. METHODS: This was a retrospective review of 99 adult patients with rTOF. Right ventricular (RV) and left ventricular (LV) function were assessed echocardiographically using the myocardial performance index (MPI). Maximal oxygen consumption (VO(2) Max) was measured during a level 1 cardiopulmonary exercise test. RESULTS: The mean age of the cohort was 34 +/- 11 years (50% females). Although most of the patients reported good functional capacity, the peak Vo(2)max was decreased at 22 +/- 6 mL/kg per minute (66% +/- 13% predicted Vo(2)max for age and sex). The mean RV and LV MPI were 0.30 +/- 0.07 and 0.42 +/- 0.09, respectively. In the multivariate model, higher RV MPI (P = .04) and LV MPI (P = .005) values, representing impaired ventricular function, were associated with diminished Vo(2)max. There was a significant correlation between the RV and LV MPI (r = 0.54, P = .001). CONCLUSIONS: Impairment of RV and LV function, as measured by MPI, is associated with diminished exercise capacity in patients with repaired tetralogy of Fallot. Furthermore, there is a linear relationship between the RV and LV function suggesting that ventricular interactions are contributing to the limited exercise capacity in this group of patients. Strategies aimed at preserving biventricular function or improving adverse ventricular interactions could help to improve functional capacity in these patients.

"The need obliged us" : culture as capacity during the Hurricane Stan emergency response. A case study from Tectitan, Huehuetenango, Guatemala

A major deficiency in disaster management plans is the assumption that pre-disaster civil-society does not have the capacity to respond effectively during crises. Following from this assumption a dominant emergency management strategy is to replace weak civil-society organizations with specialized disaster organizations that are often either military or Para-military and seek to centralize decision-making. Many criticisms have been made of this approach, but few specifically addresses disasters in the developing world. Disasters in the developing world present unique problems not seen in the developed world because they often occur in the context of compromised governments, and marginalized populations. In this context it is often community members themselves who possess the greatest capacity to respond to disasters. This paper focuses on the capacity of community groups to respond to disaster in a small town in rural Guatemala. Key informant interviews and ethnographic observations are used to reconstruct the community response to the disaster instigated by Hurricane Stan (2005) in the municipality of Tectitán in the Huehuetenango department. The interviews were analyzed using techniques adapted from grounded theory to construct a narrative of the events, and identify themes in the community’s disaster behavior. These themes are used to critique the emergency management plans advocated by the Guatemalan National Coordination for the Reduction of Disasters (CONRED). This paper argues that CONRED uncritically adopts emergency management strategies that do not account for the local realities in communities throughout Guatemala. The response in Tectitán was characterized by the formation of new organizations, whose actions and leadership structure were derived from “normal” or routine life. It was found that pre-existing social networks were resilient and easily re-oriented meet the novel needs of a crisis. New or emergent groups that formed during the disaster utilized social capital accrued by routine collective behavior, and employed organizational strategies derived from “normal” community relations. Based on the effectiveness of this response CONRED could improve its emergency planning on the local-level by utilizing the pre-existing community organizations rather than insisting that new disaster-specific organizations be formed.

Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner

Abstract Sphingosine kinases (SKs) are key enzymes regulating the production of sphingosine-1-phosphate (S1P), which determines important cell responses including cell growth and death. Here we show that renal mesangial cells isolated from wild-type, SK-1(-/-), and SK-2(-/-) mice show a differential response to apoptotic stimuli. Wild-type mesangial cells responded to staurosporine with increased DNA fragmentation and caspase-3 processing, which was enhanced in SK-1(-/-) cells. In contrast, SK-2(-/-) cells were highly resistant to staurosporine-induced apoptosis. Furthermore, the basal phosphorylation and activity of the anti-apoptotic protein kinase B (PKB) and of its substrate Bad were decreased in SK-1(-/-) but not in SK-2(-/-) cells. Upon staurosporine treatment, phosphorylation of PKB and Bad decreased in wild-type and SK-1(-/-) cells, but remained high in SK-2(-/-) cells. In addition, the anti-apoptotic Bcl-X(L) was significantly upregulated in SK-2(-/-) cells, which may further contribute to the protective state of these cells. In summary, our data show that SK-1 and SK-2 have opposite effects on the capacity of mesangial cells to resist apoptotic stimuli. This is due to differential modulation of the PKB/Bad pathway and of Bcl-X(L) expression. Thus, subtype-selective targeting of SKs will be critical when considering these enzymes as therapeutic targets for the treatment of inflammation or cancer.

Structural capacity of steel tubular cast-in-place piling

Steel tubular cast-in-place pilings are used throughout the country for many different project types. These piles are a closed-end pipe with varying wall thicknesses and outer diameters, that are driven to depth and then the core is filled with concrete. These piles are typically used for smaller bridges, or secondary structures. Mostly the piling is designed based on a resistance based method which is a function of the soil properties of which the pile is driven through, however there is a structural capacity of these members that is considered to be the upper bound on the loading of the member. This structural capacity is given by the AASHTO LRFD (2010), with two methods. These two methods are based on a composite or non-composite section. Many state agencies and corporations use the non-composite equation because it is requires much less computation and is known to be conservative. However with the trends of the time, more and more structural elements are being investigated to determine ways to better understand the mechanics of the members, which could lead to more efficient and safer designs. In this project, a set of these piling are investigated. The way the cross section reacts to several different loading conditions, along with a more detailed observation of the material properties is considered as part of this research. The evaluation consisted of testing stub sections of pile with varying sizes (10-¾”, 12-¾”), wall thicknesses (0.375”, 0.5”), and testing methods (whole compression, composite compression, push through, core sampling). These stub sections were chosen as they would represent a similar bracing length to many different soils. In addition, a finite element model was developed using ANSYS to predict the strains from the testing of the pile cross sections. This model was able to simulate the strains from most of the loading conditions and sizes that were tested. The bond between the steel shell and the concrete core, along with the concrete strength through the depth of the cross section were some of the material properties of these sections that were investigated.

Capacity optimization of a prestressed concrete railroad tie

Today the use of concrete ties is on the rise in North America as they become an economically competitive alternative to the historical industry standard wood ties, while providing performance which exceeds its competition in terms of durability and capacity. Similarly, in response to rising energy costs, there is increased demand for efficient and sustainable transportation of people and goods. One source of such transportation is the railroad. To accommodate the increased demand, railroads are constructing new track and upgrading existing track. This update to the track system will increase its capacity while making it a more reliable means of transportation compared to other alternatives. In addition to increasing the track system capacity, railroads are considering an increase in the size of the typical freight rail car to allow larger tonnage. An increase in rail car loads will in turn affect the performance requirements of the track. Due to the increased loads heavy haul railroads are considering applying to their tracks, current designs of prestressed concrete railroad ties for heavy haul applications may be undersized. In an effort to maximize tie capacity while maintaining tie geometry, fastening systems and installation equipment, a parametric study to optimize the existing designs was completed. The optimization focused on maximizing the capacity of an existing tie design through an investigation of prestressing quantity, configuration, stress levels and other material properties. The results of the parametric optimization indicate that the capacity of an existing tie can be increased most efficiently by increasing the diameter of the prestressing and concrete strength. However, researchers also found that current design specifications and procedures do not include consideration of tie behavior beyond the current tie capacity limit of cracking to the first layer of prestressing. In addition to limiting analysis to the cracking limit, failure mechanisms such as shear in deep beams at the rail seat or pullout failure of the prestressing due to lack of development length were absent from specified design procedures, but discussed in this project.

Comparison of three methods for driven pile capacity

A significant cost for foundations is the design and installation of piles when they are required due to poor ground conditions. Not only is it important that piles be designed properly, but also that the installation equipment and total cost be evaluated. To assist in the evaluation of piles a number of methods have been developed. In this research three of these methods were investigated, which were developed by the Federal Highway Administration, the US Corps of Engineers and the American Petroleum Institute (API). The results from these methods were entered into the program GRLWEAPTM to assess the pile drivability and to provide a standard base for comparing the three methods. An additional element of this research was to develop EXCEL spreadsheets to implement these three methods. Currently the Army Corps and API methods do not have publicly available software and must be performed manually, which requires that data is taken off of figures and tables, which can introduce error in the prediction of pile capacities. Following development of the EXCEL spreadsheet, they were validated with both manual calculations and existing data sets to ensure that the data output is correct. To evaluate the three pile capacity methods data was utilized from four project sites from North America. The data included site geotechnical data along with field determined pile capacities. In order to achieve a standard comparison of the data, the pile capacities and geotechnical data from the three methods were entered into GRLWEAPTM. The sites consisted of both cohesive and cohesionless soils; where one site was primarily cohesive, one was primarily cohesionless, and the other two consisted of inter-bedded cohesive and cohesionless soils. Based on this limited set of data the results indicated that the US Corps of Engineers method more closely compared with the field test data, followed by the API method to a lesser degree. The DRIVEN program compared favorably in cohesive soils, but over predicted in cohesionless material.

Long-term health-related quality of life and walking capacity of lung recipients with and without bronchiolitis obliterans syndrome

BACKGROUND: Outcome after lung transplantation (LTx) is affected by the onset of bronchiolitis obliterans syndrome (BOS) and lung function decline. Reduced health-related quality of life (HRQL) and physical mobility have been shown in patients developing BOS, but the impact on the capacity to walk is unknown. We aimed to compare the long-term HRQL and 6-minute walk test (6MWT) between lung recipients affected or not by BOS Grade > or =2. METHODS: Fifty-eight patients were prospectively followed for 5.6 +/- 2.9 years after LTx. Assessments included the St George's Respiratory Questionnaire (SGRQ) and the 6MWT, which were performed yearly. Moreover, clinical complications were recorded to estimate the proportion of the follow-up time lived without clinical intercurrences after transplant. Analyses were performed using adjusted linear regression and repeated-measures analysis of variance. RESULTS: BOS was a significant predictor of lower SGRQ scores (p < 0.01) and reduced time free of clinical complications (p = 0.001), but not of 6MWT distance (p = 0.12). At 7 years post-transplant, results were: 69.0 +/- 21.8% vs 86.9 +/- 5.6%, p < 0.05 (SGRQ); 58.5 +/- 21.6% vs 88.7 +/- 11.4%, p < 0.01 (proportion of time lived without clinical complications); and 82.2 +/- 10.9% vs 91.9 +/- 14.2%, p = 0.27 (percent of predicted 6MWT), respectively, for patients with BOS and without BOS. CONCLUSIONS: Despite significantly less time lived without clinical complications and progressive decline of self-reported health status, the capacity to walk of patients affected by BOS remained relatively stable over time. These findings may indicate that the development of moderate to severe BOS does not prevent lung recipients from walking independently and pursuing an autonomous life.

EXAMINING POLICY CAPACITY INITIATIVES WITHIN CLIMATE CHANGE FRAMEWORKS IN THREE US AND CANADIAN SECTORS USING NVIVO CONTENT ANALYSIS

The climate change narrative has changed from one of mitigation to one of adaptation. Governments around the world have created climate change frameworks which address how the country can better cope with the expected and unexpected changes due to global climate change. In an effort to do so, federal governments of Canada and the United States, as well as some provinces and states within these countries, have created detailed documents which outline what steps must be taken to adapt to these changes. However, not much is mentioned about how these steps will be translated in to policy, and how that policy will eventually be implemented. To examine the ability of governments to acknowledge and incorporate the plethora of scientific information to policy, consideration must be made for policy capacity. This report focuses on three sectors: water supply and demand; drought and flood planning; and forest and grassland ecosystems, and the word ‘capacity’ as related to nine different forms of policy capacity acknowledged in these frameworks. Qualitative content analysis using NVivo was carried out on fifty four frameworks and the results obtained show that there is a greater consideration for managerial capacity compared to analytical or political capacity. The data also indicated that although there were more Canadian frameworks which referred to policy capacity, the frameworks from the United States actually considered policy capacity to a greater degree.

Strategic Emergency department design: An approach to capacity planning in healthcare provision in overcrowded emergency rooms

Healthcare professionals and the public have increasing concerns about the ability of emergency departments to meet current demands. Increased demand for emergency services, mainly caused by a growing number of minor and moderate injuries has reached crisis proportions, especially in the United Kingdom. Numerous efforts have been made to explore the complex causes because it is becoming more and more important to provide adequate healthcare within tight budgets. Optimisation of patient pathways in the emergency department is therefore an important factor. This paper explores the possibilities offered by dynamic simulation tools to improve patient pathways using the emergency department of a busy university teaching hospital in Switzerland as an example.

Heart rate response determines long term exercise capacity after heart transplantation

BACKGROUND: Exercise capacity after heart transplantation (HTx) remains limited despite normal left ventricular systolic function of the allograft. Various clinical and haemodynamic parameters are predictive of exercise capacity following HTx. However, the predictive significance of chronotropic competence has not been demonstrated unequivocally despite its immediate relevance for cardiac output. AIMS: This study assesses the predictive value of various clinical and haemodynamic parameters for exercise capacity in HTx recipients with complete chronotropic competence evolving within the first 6 postoperative months. METHODS: 51 patients were enrolled in this exercise study. Patients were included when at least >6 months after HTx and without negative chronotropic medication or factors limiting exercise capacity such as significant transplant vasculopathy or allograft rejection. Clinical parameters were obtained by chart review, haemodynamic parameters from current cardiac catheterisation, and exercise capacity was assessed by treadmill stress testing. A stepwise multiple regression model analysed the proportion of the variance explained by the predictive parameters. RESULTS: The mean age of these 51 HTx recipients was 55.4 +/- 13.2 yrs on inclusion, 42 pts were male and the mean time interval after cardiac transplantation was 5.1 +/- 2.8 yrs. Five independent predictors explained 47.5% of the variance observed for peak exercise capacity (adjusted R2 = 0.475). In detail, heart rate response explained 31.6%, male gender 5.2%, age 4.1%, pulmonary vascular resistance 3.7%, and body-mass index 2.9%. CONCLUSION: Heart rate response is one of the most important predictors of exercise capacity in HTx recipients with complete chronotropic competence and without relevant transplant vasculopathy or acute allograft rejection.

Diastolic dysfunction of the cardiac allograft and maximal exercise capacity

BACKGROUND: Peak oxygen uptake (peak Vo(2)) is an established integrative measurement of maximal exercise capacity in cardiovascular disease. After heart transplantation (HTx) peak Vo(2) remains reduced despite normal systolic left ventricular function, which highlights the relevance of diastolic function. In this study we aim to characterize the predictive significance of cardiac allograft diastolic function for peak Vo(2). METHODS: Peak Vo(2) was measured using a ramp protocol on a bicycle ergometer. Left ventricular (LV) diastolic function was assessed with tissue Doppler imaging sizing the velocity of the early (Ea) and late (Aa) apical movement of the mitral annulus, and conventional Doppler measuring early (E) and late (A) diastolic transmitral flow propagation. Correlation coefficients were calculated and linear regression models fitted. RESULTS: The post-transplant time interval of the 39 HTxs ranged from 0.4 to 20.1 years. The mean age of the recipients was 55 +/- 14 years and body mass index (BMI) was 25.4 +/- 3.9 kg/m(2). Mean LV ejection fraction was 62 +/- 4%, mean LV mass index 108 +/- 22 g/m(2) and mean peak Vo(2) 20.1 +/- 6.3 ml/kg/min. Peak Vo(2) was reduced in patients with more severe diastolic dysfunction (pseudonormal or restrictive transmitral inflow pattern), or when E/Ea was > or =10. Peak Vo(2) correlated with recipient age (r = -0.643, p < 0.001), peak heart rate (r = 0.616, p < 0.001) and BMI (r = -0.417, p = 0.008). Of all echocardiographic measurements, Ea (r = 0.561, p < 0.001) and Ea/Aa (r = 0.495, p = 0.002) correlated best. Multivariate analysis identified age, heart rate, BMI and Ea/Aa as independent predictors of peak Vo(2). CONCLUSIONS: Diastolic dysfunction is relevant for the limitation of maximal exercise capacity after HTx.

In vitro comparison of the complement-scavenging capacity of different intravenous immunoglobulin preparations

BACKGROUND AND OBJECTIVES: Complement inhibition is considered important in the mechanism of action of intravenous immunoglobulin (IVIG) in a number of inflammatory and autoimmune disorders. The capacity of different IVIG preparations to 'scavenge' activated C3 and thereby inhibit complement activation was assessed by a new in vitro assay. MATERIALS AND METHODS: Diluted human serum as a complement source, with or without addition of different concentrations of IVIG, was incubated in microtitre plates coated with heat-aggregated human IgG. Complement scavenging was measured by detecting reduced C3 binding and determining fluid phase C3b-IgG complex formation. Complement activation induced by the IVIG preparations was measured as C5a formation. RESULTS: All IVIG preparations exhibited a dose-dependent inhibition of C3b deposition, correlating strongly with binding of C3b to fluid-phase IgG, but the extent of complement scavenging varied considerably between different IVIG preparations. At an IVIG concentration of 0.9 mg/ml, the inhibition of C3b deposition ranged from 72 +/- 16% to 22 +/- 4.1%. The reduction of C3b deposition on the complement-activating surface was not due to IVIG-induced complement activation in the fluid phase, as shown by the low C5a formation in the presence of serum. CONCLUSION: In vitro analysis allows comparison of the complement-inhibitory properties of IVIG preparations. The extent of complement scavenging varies between the products.