Improvement of cardiovascular risk prediction: time to review current knowledge, debates, and fundamentals on how to assess test characteristics.

Cardiovascular risk assessment might be improved with the addition of emerging, new tests derived from atherosclerosis imaging, laboratory tests or functional tests. This article reviews relative risk, odds ratios, receiver-operating curves, posttest risk calculations based on likelihood ratios, the net reclassification improvement and integrated discrimination. This serves to determine whether a new test has an added clinical value on top of conventional risk testing and how this can be verified statistically. Two clinically meaningful examples serve to illustrate novel approaches. This work serves as a review and basic work for the development of new guidelines on cardiovascular risk prediction, taking into account emerging tests, to be proposed by members of the 'Taskforce on Vascular Risk Prediction' under the auspices of the Working Group 'Swiss Atherosclerosis' of the Swiss Society of Cardiology in the future.

Photodynamic Diagnosis of Non-muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data.

BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Alternatives for Rural Roads, HR-242, 1989

Much of the nation's rural road system is deteriorating. Many of the roads were built in the 1880s and 1890s with the most recent upgrading done in the 1940s and 1950s. Consequently, many roads and bridges do not have the capacity for the increased loads, speed, and frequent use of today's vehicles. Because of the growing demands and a dense county road system (inherited from the land settlement policies two centuries ago), revenue available to counties is inadequate to upgrade andmaintain the present system. Either revenue must be increased - an unpopular option - or costs must be reduced. To examine cost-saving options, Iowa State University conducted a study of roads and bridges in three 100 square mile areas in Iowa: • A suburban area • A rural area with a large number of paved roads, few bridges, and a high agricultural tax base and •A more rural area in a hilly terrain with many bridges and gravel roads, and a low agricultural tax base. A cost-benefit analysis was made on the present road system in these areas on such options as abandoning roads with limited use, converting some to private drives, and reducing maintenance on these types of roads. In only a few instances does abandonment of low traffic volume roads produce cost savings for counties and abutting land owners that exceed the additional travel costs to the public. In this study, the types of roads that produced net savings when abandoned were: • A small percentage (less than 5 percent) of the nonpaved county roads in the suburban area. However, net savings were very small. Cost savings from reducing the county road system in urbanized areas are very limited. • Slightly more than 5 percent of the nonpaved county roads in the most rural area that had a small number of paved county roads. • More than 12 percent of the nonpaved roads in the rural area that had a relatively large number of paved county and state roads. Converting low-volume roads to low-maintenance or Service B roads produces the largest savings of all solutions considered. However, future bridge deterioration and county liability on Service B roads are potential problems. Converting low-volume roads to private drives also produces large net savings. Abandonment of deadend roads results in greater net savings than continuous roads. However, this strategy shifts part of the public maintenance burden to land owners. Land owners also then become responsible for accident liability. Reconstruction to bring selected bridges with weight restrictions up to legal load limits reduces large truck and tractor-wagon mileage and costs. However, the reconstruction costs exceeded the reduction in travel costs. Major sources of vehicle miles on county roads are automobiles used for household purposes and pickup truck travel for farm purposes. Farm-related travel represents a relatively small percent of total travel miles, but a relatively high percentage of total travel costs.

Systems analysis of MVA-C induced immune response reveals its significance as a vaccine candidate against HIV/AIDS of clade C.

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world.

A Computer Based Information System for County Equipment Cost Records, Interim Report, HR-173, 1975

This report describes the work accomplished to date on research project HR-173, A Computer Based Information System for County Equipment Cost Records, and presents the initial design for this system. The specific topics discussed here are findings from the analysis of information needs, the system specifications developed from these findings, and the proposed system design based upon the system specifications. The initial system design will include tentative input designs for capturing input data, output designs to show the output formats and the items to be output for use in decision making, file design showing the organization of information to be kept on each piece of equipment in the computer data file, and general system design explaining how the entire system will operate. The Steering Committee appointed by Iowa Highway Research Board is asked to study this report, make appropriate suggestions, and give approval to the proposed design subject to any suggestions made. This approval will permit the designer to proceed promptly with the development of the computer program implementation phase of the design.

Optimizing Pavement Base, Subbase, and Subgrade Layers for Cost and Performance of Local Roads, TR-640

This report is one of two products for this project with the other being a design guide. This report describes test results and comparative analysis from 16 different portland cement concrete (PCC) pavement sites on local city and county roads in Iowa. At each site the surface conditions of the pavement (i.e., crack survey) and foundation layer strength, stiffness, and hydraulic conductivity properties were documented. The field test results were used to calculate in situ parameters used in pavement design per SUDAS and AASHTO (1993) design methodologies. Overall, the results of this study demonstrate how in situ and lab testing can be used to assess the support conditions and design values for pavement foundation layers and how the measurements compare to the assumed design values. The measurements show that in Iowa, a wide range of pavement conditions and foundation layer support values exist. The calculated design input values for the test sites (modulus of subgrade reaction, coefficient of drainage, and loss of support) were found to be different than typically assumed. This finding was true for the full range of materials tested. The findings of this study support the recommendation to incorporate field testing as part of the process to field verify pavement design values and to consider the foundation as a design element in the pavement system. Recommendations are provided in the form of a simple matrix for alternative foundation treatment options if the existing foundation materials do not meet the design intent. The PCI prediction model developed from multi-variate analysis in this study demonstrated a link between pavement foundation conditions and PCI. The model analysis shows that by measuring properties of the pavement foundation, the engineer will be able to predict long term performance with higher reliability than by considering age alone. This prediction can be used as motivation to then control the engineering properties of the pavement foundation for new or re-constructed PCC pavements to achieve some desired level of performance (i.e., PCI) with time.

Does unemployment hurt less if there is more of it around? A panel analysis of life satisfaction in Germany and Switzerland

This paper examines the existence of a habituation effect to unemployment: Do theunemployed suffer less from job loss if unemployment is more widespread, if their ownunemployment lasts longer and if unemployment is a recurrent experience? Theunderlying idea is that unemployment hysteresis may operate through a sociologicalchannel: if many people in the community lose their job and remain unemployed over anextended period, the psychological cost of being unemployed diminishes and the pressureto accept a new job declines. We analyze this question with individual-level data from theGerman Socio-Economic Panel (1984-2009) and the Swiss Household Panel (2000-2009). We find no evidence for a mitigating effect of high surrounding unemployment onunemployed individuals' subjective well-being: Becoming unemployed hurts as muchwhen regional unemployment is high as when it is low. Likewise, the strongly harmfulimpact of being unemployed on well-being does not wear off over time, nor do repeatedepisodes of unemployment make it any better. It thus appears doubtful that anunemployment shock becomes persistent because the unemployed become used to, andhence reasonably content with, being without a job.

Concrete Pavement Mixture Design and Analysis (MDA): Development and Evaluation of Vibrating Kelly Ball Test (VKelly Test) for the Workability of Concrete, 2015

Due to the low workability of slipform concrete mixtures, the science of rheology is not strictly applicable for such concrete. However, the concept of rheological behavior may still be considered useful. A novel workability test method (Vibrating Kelly Ball or VKelly test) that would quantitatively assess the responsiveness of a dry concrete mixture to vibration, as is desired of a mixture suitable for slipform paving, was developed and evaluated. The objectives of this test method are for it to be cost-effective, portable, and repeatable while reporting the suitability of a mixture for use in slipform paving. The work to evaluate and refine the test was conducted in three phases: 1. Assess whether the VKelly test can signal variations in laboratory mixtures with a range of materials and proportions 2. Run the VKelly test in the field at a number of construction sites 3. Validate the VKelly test results using the Box Test developed at Oklahoma State University for slipform paving concrete The data collected to date indicate that the VKelly test appears to be suitable for assessing a mixture’s response to vibration (workability) with a low multiple operator variability. A unique parameter, VKelly Index, is introduced and defined that seems to indicate that a mixture is suitable for slipform paving when it falls in the range of 0.8 to 1.2 in./√s.

On the Selection of Non-Invasive Methods Based on Speech Analysis Oriented to Automatic Alzheimer Disease Diagnosis

The work presented here is part of a larger study to identify novel technologies and biomarkers for early Alzheimer disease (AD) detection and it focuses on evaluating the suitability of a new approach for early AD diagnosis by non-invasive methods. The purpose is to examine in a pilot study the potential of applying intelligent algorithms to speech features obtained from suspected patients in order to contribute to the improvement of diagnosis of AD and its degree of severity. In this sense, Artificial Neural Networks (ANN) have been used for the automatic classification of the two classes (AD and control subjects). Two human issues have been analyzed for feature selection: Spontaneous Speech and Emotional Response. Not only linear features but also non-linear ones, such as Fractal Dimension, have been explored. The approach is non invasive, low cost and without any side effects. Obtained experimental results were very satisfactory and promising for early diagnosis and classification of AD patients.

Alzheimer disease diagnosis based on automatic spontaneous speech analysis

Alzheimer’s disease (AD) is the most prevalent form of progressive degenerative dementia and it has a high socio-economic impact in Western countries, therefore is one of the most active research areas today. Its diagnosis is sometimes made by excluding other dementias, and definitive confirmation must be done trough a post-mortem study of the brain tissue of the patient. The purpose of this paper is to contribute to im-provement of early diagnosis of AD and its degree of severity, from an automatic analysis performed by non-invasive intelligent methods. The methods selected in this case are Automatic Spontaneous Speech Analysis (ASSA) and Emotional Temperature (ET), that have the great advantage of being non invasive, low cost and without any side effects.

Efficacy of in-hospital multidimensional interventions of secondary prevention after acute coronary syndrome: a systematic review and meta-analysis

BACKGROUND: Secondary prevention programs for patients experiencing an acute coronary syndrome have been shown to be effective in the outpatient setting. The efficacy of in-hospital prevention interventions administered soon after acute cardiac events is unclear. We performed a systematic review and meta-analysis to determine whether in-hospital, patient-level interventions targeting multiple cardiovascular risk factors reduce all-cause mortality after an acute coronary syndrome. METHODS AND RESULTS: Using a prespecified search strategy, we included controlled clinical trials and before-after studies of secondary prevention interventions with at least a patient-level component (ie, education, counseling, or patient-specific order sets) initiated in hospital with outcomes of mortality, readmission, or reinfarction rates in acute coronary syndrome patients. We classified the interventions as patient-level interventions with or without associated healthcare provider-level interventions and/or system-level interventions. Twenty-six studies met our inclusion criteria. The summary estimate of 14 studies revealed a relative risk of all-cause mortality of 0.79 (95% CI, 0.69 to 0.92; n=37,585) at 1 year. However, the apparent benefit depended on study design and level of intervention. The before-after studies suggested reduced mortality (relative risk [RR], 0.77; 95% CI, 0.66 to 0.90; n=3680 deaths), whereas the RR was 0.96 (95% CI, 0.64 to 1.44; n=99 deaths) among the controlled clinical trials. Only interventions including a provider- or system-level intervention suggested reduced mortality compared with patient-level-only interventions. CONCLUSIONS: The evidence for in-hospital, patient-level interventions for secondary prevention is promising but not definitive because only before-after studies suggest a significant reduction in mortality. Future research should formally test which components of interventions provide the greatest benefit.

Populations with elevated mutation load do not benefit from the operation of sexual selection.

Theory predicts that if most mutations are deleterious to both overall fitness and condition-dependent traits affecting mating success, sexual selection will purge mutation load and increase nonsexual fitness. We explored this possibility with populations of mutagenized Drosophila melanogaster exhibiting elevated levels of deleterious variation and evolving in the presence or absence of male-male competition and female choice. After 60 generations of experimental evolution, monogamous populations exhibited higher total reproductive output than polygamous populations. Parental environment also affected fitness measures - flies that evolved in the presence of sexual conflict showed reduced nonsexual fitness when their parents experienced a polygamous environment, indicating trans-generational effects of male harassment and highlighting the importance of a common garden design. This cost of parental promiscuity was nearly absent in monogamous lines, providing evidence for the evolution of reduced sexual antagonism. There was no overall difference in egg-to-adult viability between selection regimes. If mutation load was reduced by the action of sexual selection in this experiment, the resultant gain in fitness was not sufficient to overcome the costs of sexual antagonism.

Population based screening - the difficulty of how to do more good than harm and how to achieve it.

Screening people without symptoms of disease is an attractive idea. Screening allows early detection of disease or elevated risk of disease, and has the potential for improved treatment and reduction of mortality. The list of future screening opportunities is set to grow because of the refinement of screening techniques, the increasing frequency of degenerative and chronic diseases, and the steadily growing body of evidence on genetic predispositions for various diseases. But how should we decide on the diseases for which screening should be done and on recommendations for how it should be implemented? We use the examples of prostate cancer and genetic screening to show the importance of considering screening as an ongoing population-based intervention with beneficial and harmful effects, and not simply the use of a test. Assessing whether screening should be recommended and implemented for any named disease is therefore a multi-dimensional task in health technology assessment. There are several countries that already use established processes and criteria to assess the appropriateness of screening. We argue that the Swiss healthcare system needs a nationwide screening commission mandated to conduct appropriate evidence-based evaluation of the impact of proposed screening interventions, to issue evidence-based recommendations, and to monitor the performance of screening programmes introduced. Without explicit processes there is a danger that beneficial screening programmes could be neglected and that ineffective, and potentially harmful, screening procedures could be introduced.

Low-Cost Rural Surface Alternatives: Demonstration Project, TR-664, 2015

The goals of this project were to implement several stabilization methods for preventing or mitigating freeze-thaw damage to granular surfaced roads and identify the most effective and economical methods for the soil and climate conditions of Iowa. Several methods and technologies identified as potentially suitable for Iowa were selected from an extensive analysis of existing literature provided with Iowa Highway Research Board (IHRB) Project TR-632. Using the selected methods, demonstration sections were constructed in Hamilton County on a heavily traveled two-mile section of granular surfaced road that required frequent maintenance during previous thawing periods. Construction procedures and costs of the demonstration sections were documented, and subsequent maintenance requirements were tabulated through two seasonal freeze-thaw periods. Extensive laboratory and field tests were performed prior to construction, as well as before and after the two seasonal freeze-thaw periods, to monitor the performance of the demonstration sections. A weather station was installed at the project site and temperature sensors were embedded in the subgrade to monitor ground temperatures up to a depth of 5 ft and determine the duration and depths of ground freezing and thawing. An economic analysis was performed using the documented construction and maintenance costs, and the estimated cumulative costs per square yard were projected over a 20-year timeframe to determine break-even periods relative to the cost of continuing current maintenance practices. Overall, the sections with biaxial geogrid or macadam base courses had the best observed freeze-thaw performance in this study. These two stabilization methods have larger initial costs and longer break-even periods than aggregate columns, but counties should also weigh the benefits of improved ride quality and savings that these solutions can provide as excellent foundations for future paving or surface upgrades.

Robust parametric indirect estimates of the expected cost of a hospital stay with covariates and censored data.

We consider the problem of estimating the mean hospital cost of stays of a class of patients (e.g., a diagnosis-related group) as a function of patient characteristics. The statistical analysis is complicated by the asymmetry of the cost distribution, the possibility of censoring on the cost variable, and the occurrence of outliers. These problems have often been treated separately in the literature, and a method offering a joint solution to all of them is still missing. Indirect procedures have been proposed, combining an estimate of the duration distribution with an estimate of the conditional cost for a given duration. We propose a parametric version of this approach, allowing for asymmetry and censoring in the cost distribution and providing a mean cost estimator that is robust in the presence of extreme values. In addition, the new method takes covariate information into account.