1980 railroad traffic density, Iowa, 1982

This map shows railroad traffic usage by Iowa Rail Carriers.

How reliable is an undetectable viral load?

OBJECTIVES: An article by the Swiss AIDS Commission states that patients with stably suppressed viraemia [i.e. several successive HIV-1 RNA plasma concentrations (viral loads, VL) below the limits of detection during 6 months or more of highly active antiretroviral therapy (HAART)] are unlikely to be infectious. Questions then arise: how reliable is the undetectability of the VL, given the history of measures? What factors determine reliability? METHODS: We assessed the probability (henceforth termed reliability) that the n+1 VL would exceed 50 or 1000 HIV-1 RNA copies/mL when the nth one had been <50 copies/mL in 6168 patients of the Swiss HIV Cohort Study who were continuing to take HAART between 2003 and 2007. General estimating equations were used to analyse potential factors of reliability. RESULTS: With a cut-off at 50 copies/mL, reliability was 84.5% (n=1), increasing to 94.5% (n=5). Compliance, the current type of HAART and the first antiretroviral therapy (ART) received (HAART or not) were predictive factors of reliability. With a cut-off at 1000 copies/mL, reliability was 97.5% (n=1), increasing to 99.1% (n=4). Chart review revealed that patients had stopped their treatment, admitted to major problems with compliance or were taking non-HAART ART in 72.2% of these cases. Viral escape caused by resistance was found in 5.6%. No explanation was found in the charts of 22.2% of cases. CONCLUSIONS: After several successive VLs at <50 copies/mL, reliability reaches approximately 94% with a cut-off of 50 copies/mL and approximately 99% with a cut-off at 1000 copies/mL. Compliance is the most important factor predicting reliability.

Evaluation of Low Cost Traffic Calming for Rural Communities – Phase II [Updated], TR-630, October, 2013

The main goal of the research described in this report was to evaluate countermeasures that agencies can use to reduce speeds as drivers enter rural communities located on high-speed roadways. The objectives of this study were as follows: * Identify and summarize countermeasures used to manage speeds in transition zones * Demonstrate the effectiveness of countermeasures that are practical for high- to low-speed transition zones * Acquire additional information about countermeasures that may show promise but lack sufficient evidence of effectiveness * Develop an application toolbox to assist small communities in selecting appropriate transition zones and effective countermeasures for entrances to small rural communities The team solicited small communities that were interested in participating in the Phase II study and several communities were also recommended. The treatments evaluated were selected by carefully considering traffic-calming treatments that have been used effectively in other countries for small rural communities, as well as the information gained from the first phase of the project. The treatments evaluated are as follows: * Transverse speed bars * Colored entrance treatment * Temporary island * Radar-activated speed limit sign * Speed feedback sign The toolbox publication and four focused tech briefs also cover the results of this work.

Association between mannose-binding lectin deficiency and cytornegalovirus infection course after organ transplantation.

Background: Mannose binding lectin (MBL) is an innate humoral immune effector and MBL defi ciency has been suggested as a risk factor for the development of certain viral infections. However, there is no data about the possible association between MBL defi ciency and CMV, especially after organ transplantation. Methods: We measured MBL levels in 16 kidney transplant recipients with highrisk CMV serostatus (D+/R-) who received valganciclovir prophylaxis for 3 months (Study 1). In addition, MBL levels were retrospectively assayed in 55 recipients from a previous study of organ transplant recipients managed preemptively (Study 2). In Study 2, protracted CMV infection was associated with recipient CMV seronegativity, increasing age, and high viral load during the initial episode. In both studies, MBL defi ciency was diagnosed if MBL levels were <500 ng/ml. Results: In Study 1, after a follow-up of 12 months, 7 out of 16 patients developed CMV disease, 4 patients developed asymptomatic CMV infection, and 5 patients never developed any sign of CMV replication. Overall, 9/16 patients (56%) had MBL defi ciency: 5/7 (71%) of patients with CMV disease, 4/4 (100%) of patients with asymptomatic CMV infection, and 0/5 (0%) of patients without CMV infection (p=0.005, between CMV infection/disease versus no infection). Median MBL concentrations were higher in patients without CMV infection than in those with CMV infection (p<0.005). In Study 2, among 30 patients with CMV infection, 9/25 (36%) patients without MBL defi ciency had a protracted course, while 4/5 (80%) with MBL defi ciency did so (p=0.07). Conclusion: Data from two separate patient populations suggest that MBL defi ciency may be a signifi cant risk factor for late CMV disease/infection after prophylaxis, and protracted infection after preemptive treatment. This suggests a role for MBL in the control of CMV infection after organ transplantation.

Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals.

OBJECTIVES: Toll-like receptors (TLRs) are innate immune sensors that are integral to resisting chronic and opportunistic infections. Mounting evidence implicates TLR polymorphisms in susceptibilities to various infectious diseases, including HIV-1. We investigated the impact of TLR single nucleotide polymorphisms (SNPs) on clinical outcome in a seroincident cohort of HIV-1-infected volunteers. DESIGN: We analyzed TLR SNPs in 201 antiretroviral treatment-naive HIV-1-infected volunteers from a longitudinal seroincident cohort with regular follow-up intervals (median follow-up 4.2 years, interquartile range 4.4). Participants were stratified into two groups according to either disease progression, defined as peripheral blood CD4(+) T-cell decline over time, or peak and setpoint viral load. METHODS: Haplotype tagging SNPs from TLR2, TLR3, TLR4, and TLR9 were detected by mass array genotyping, and CD4(+) T-cell counts and viral load measurements were determined prior to antiretroviral therapy initiation. The association of TLR haplotypes with viral load and rapid progression was assessed by multivariate regression models using age and sex as covariates. RESULTS: Two TLR4 SNPs in strong linkage disequilibrium [1063 A/G (D299G) and 1363 C/T (T399I)] were more frequent among individuals with high peak viral load compared with low/moderate peak viral load (odds ratio 6.65, 95% confidence interval 2.19-20.46, P < 0.001; adjusted P = 0.002 for 1063 A/G). In addition, a TLR9 SNP previously associated with slow progression was found less frequently among individuals with high viral setpoint compared with low/moderate setpoint (odds ratio 0.29, 95% confidence interval 0.13-0.65, P = 0.003, adjusted P = 0.04). CONCLUSION: This study suggests a potentially new role for TLR4 polymorphisms in HIV-1 peak viral load and confirms a role for TLR9 polymorphisms in disease progression.

Predicting the deleterious effects of mutation load in fragmented populations.

Human-induced habitat fragmentation constitutes a major threat to biodiversity. Both genetic and demographic factors combine to drive small and isolated populations into extinction vortices. Nevertheless, the deleterious effects of inbreeding and drift load may depend on population structure, migration patterns, and mating systems and are difficult to predict in the absence of crossing experiments. We performed stochastic individual-based simulations aimed at predicting the effects of deleterious mutations on population fitness (offspring viability and median time to extinction) under a variety of settings (landscape configurations, migration models, and mating systems) on the basis of easy-to-collect demographic and genetic information. Pooling all simulations, a large part (70%) of variance in offspring viability was explained by a combination of genetic structure (F(ST)) and within-deme heterozygosity (H(S)). A similar part of variance in median time to extinction was explained by a combination of local population size (N) and heterozygosity (H(S)). In both cases the predictive power increased above 80% when information on mating systems was available. These results provide robust predictive models to evaluate the viability prospects of fragmented populations.

Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial.

BACKGROUND: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24(Gag), in adults infected with HIV-1. METHODS: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 10(6) cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, the UK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo. Group allocation was masked from participants and investigators. Four primary immunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were given intradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption. Analyses were by modified intention to treat: all participants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed. The 52 week follow-up period was completed in June, 2011. For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate. This study is registered with ClinicalTrials.gov, number NCT00659789. FINDINGS: 174 individuals were screened; because of slow recruitment, enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28. Of the participants who resumed cART, 30 (34%) were in the Vacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4 counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to 1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23 100 copies per mL Vacc-4x vs 71 800 copies per mL placebo; p=0·025) and week 52 (median 19 550 copies per mL vs 51 000 copies per mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic, inducing proliferative responses in both CD4 and CD8 T-cell populations. INTERPRETATION: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worth consideration in future HIV-cure investigative strategies. FUNDING: Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA.

Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection.

BACKGROUND: Visceral leishmaniasis is a parasitic disease associated with high mortality. The most important foci of visceral leishmaniasis in Ethiopia are in the Northwest and are predominantly associated with high rates of HIV co-infection. Co-infection of visceral leishmaniasis patients with HIV results in higher mortality, treatment failure and relapse. We have previously shown that arginase, an enzyme associated with immunosuppression, was increased in patients with visceral leishmaniasis and in HIV seropositive patients; further our results showed that high arginase activity is a marker of disease severity. Here, we tested the hypothesis that increased arginase activities associated with visceral leishmaniasis and HIV infections synergize in patients co-infected with both pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with visceral leishmaniasis and a cohort of patients with visceral leishmaniasis and HIV infection from Gondar, Northwest Ethiopia, and recorded and compared their clinical data. Further, we measured the levels of arginase activity in the blood of these patients and identified the phenotype of arginase-expressing cells. Our results show that CD4(+) T cell counts were significantly lower and the parasite load in the spleen was significantly higher in co-infected patients. Moreover, our results demonstrate that arginase activity was significantly higher in peripheral blood mononuclear cells and plasma of co-infected patients. Finally, we identified the cells-expressing arginase in the PBMCs as low-density granulocytes. CONCLUSION: Our results suggest that increased arginase might contribute to the poor disease outcome characteristic of patients with visceral leishmaniasis and HIV co-infection.

Load Ratings for Standard Bridges, HR-239 Phase IV, 2008

In this report, sixteen secondary and primary bridge standards for two types of bridges are rated for AASHTO HS20-44 vehicle configuration utilizing Load Factor methodology. The ratings apply only to those bridges which: (1) are built according to the applicable bridge standard plans, (2) have no structural deterioration or damage, and (3) have no added wearing surface in excess of one-half inch integral wearing surface.

Development of a New Process for Determining Design Year Traffic Demands, TR-528, 2007

Researchers should continuously ask how to improve the models we rely on to make financial decisions in terms of the planning, design, construction, and maintenance of roadways. This project presents an alternative tool that will supplement local decision making but maintain a full appreciation of the complexity and sophistication of today’s regional model and local traffic impact study methodologies. This alternative method is tailored to the desires of local agencies, which requested a better, faster, and easier way to evaluate land uses and their impact on future traffic demands at the sub-area or project corridor levels. A particular emphasis was placed on scenario planning for currently undeveloped areas. The scenario planning tool was developed using actual land use and roadway information for the communities of Johnston and West Des Moines, Iowa. Both communities used the output from this process to make regular decisions regarding infrastructure investment, design, and land use planning. The City of Johnston case study included forecasting future traffic for the western portion of the city within a 2,600-acre area, which included 42 intersections. The City of West Des Moines case study included forecasting future traffic for the city’s western growth area covering over 30,000 acres and 331 intersections. Both studies included forecasting a.m. and p.m. peak-hour traffic volumes based upon a variety of different land use scenarios. The tool developed took goegraphic information system (GIS)-based parcel and roadway information, converted the data into a graphical spreadsheet tool, allowed the user to conduct trip generation, distribution, and assignment, and then to automatically convert the data into a Synchro roadway network which allows for capacity analysis and visualization. The operational delay outputs were converted back into a GIS thematic format for contrast and further scenario planning. This project has laid the groundwork for improving both planning and civil transportation decision making at the sub-regional, super-project level.

Non-Corrosive Tie Reinforcing and Dowel Bars for Highway Pavement Slabs, HR-343, 1993

The use of non-metallic load transfer and reinforcement devices for concrete highway pavements is a possible alternative to avoid corrosion problems related to the current practice of steel materials. Laboratory and field testing of highway pavement dowel bars, made of both steel and fiber composite materials, and fiber composite tie rods were carried out in this research investigation. Fatigue, static, and dynamic testing was performed on full-scale concrete pavement slabs which were supported by a simulated subgrade and which included a single transverse joint. The bahavior of the full-scale specimens with both steel and fiber composite dowels placed in the test joints was monitored during several million load cycles which simulated truck traffic at a transverse joint. Static bond tests were conducted on fiber composite tie rods to determine the required embedment length. These tests took the form of bending tests which included curvature and shear in the embedment zone and pullout tests which subjected the test specimen to axial tension only. Fiber composite dowel bars were placed at two transverse joints during construction of a new concrete highway pavement in order to evaluate their performance under actual field conditions. Fiber composite tie rods were also placed in the longitudinal joint between the two fiber composite doweled transverse joints.

Load Ratings for Standard Bridges, HR-239 Phase III, 1998

In this report, 25 secondary bridge standards for three types of bridges are rated for the AASHTO HS20-44 vehicle configuration and five typical Iowa legal vehicles. The ratings apply only to those bridges which: (1) are built according to the applicable bridge standard plans, (2) have no structural deterioration or damage, and (3) have no added wearing surface in excess of 0.5-in. (1.27-cm) integral wearing surface. Appendix A contains the results of the original October 1982 report on load ratings for standard bridges.

Lateral Load Resistance of Diaphragms in Prestressed Concrete Girder Bridges, HR-319, 1991

Each year several prestressed concrete girder bridges in Iowa and other states are struck and damaged by vehicles with loads too high to pass under the bridge. Whether or not intermediate diaphragms play a significant role in reducing the effect of these unusual loading conditions has often been a topic of discussion. A study of the effects of the type and location of intermediate diaphragms in prestressed concrete girder bridges when the bridge girder flanges were subjected to various levels of vertical and horizontal loading was undertaken. The purpose of the research was to determine whether steel diaphragms of any conventional configuration can provide adequate protection to minimize the damage to prestressed concrete girders caused by lateral loads, similar to the protection provided by the reinforced concrete intermediate diaphragms presently being used by the Iowa Department of Transportation. The research program conducted and described in this report included the following: A comprehensive literature search and survey questionnaire were undertaken to define the state-of-the-art in the use of intermediate diaphragms in prestressed concrete girder bridges. A full scale, simple span, restressed concrete girder bridge model, containing three beams was constructed and tested with several types of intermediate diaphragms located at the one-third points of the span or at the mid-span. Analytical studies involving a three-dimensional finite element analysis model were used to provide additional information on the behavior of the experimental bridge. The performance of the bridge with no intermediate diaphragms was quite different than that with intermediate diaphragms in place. All intermediate diaphragms tested had some effect in distributing the loads to the slab and other girders, although some diaphragm types performed better than others. The research conducted has indicated that the replacement of the reinforced concrete intermediate diaphragms currently being used in Iowa with structural steel diaphragms may be possible.

Liability and Traffic Control Considerations for Low Water Stream Crossings, HR-218, 1981

The current shortage of highway funds precludes the immediate replacement of most of the bridges that have been evaluated as structurally deficient or functionally obsolete or both. A low water stream crossing (LWSC) affords an economical alternative to the replacement of a bridge with another bridge in many instances. However, the potential liability that might be incurred from the use of LWSCs has served as a deterrent to their use. Nor have guidelines for traffic control devices been developed for specific application to LWSCs. This research addressed the problems of liability and traffic control associated with the use of LWSCs. Input to the findings from this research was provided by several persons contacted by telephone plus 189 persons who responded to a questionnaire concerning their experience with LWSCs. It was concluded from this research that a significant potential for accidents and liability claims could result from the use of LWSCs. However, it was also concluded that this liability could be reduced to within acceptable limits if adequate warning of the presence of an LWSC were afforded to road users. The potential for accidents and liability could further be reduced if vehicular passage over an LWSC were precluded during periods when the road was flooded. Under these conditions, it is believed, the potential for liability from the use of an LWSC on an unpaved, rural road would be even less than that resulting from the continuing use of an inadequate bridge. The signs recommended for use in advance of an LWSC include two warning signs and one regulatory sign with legends as follows: FLOOD AREA AHEAD, IMPASSABLE DURING HIGH WATER, DO NOT ENTER WHEN FLOODED. Use of the regulatory sign would require an appropriate resolution by the Board of Supervisors having responsibility for a county road. Other recommendations include the optional use of either a supple mental distance advisory plate or an advisory speed plate, or both, under circumstances where these may be needed. It was also recommended HR-218 Liability & Traffic Control Considerations for Low Water Stream Crossings that LWSCs be used only on unpaved roads and that they not be used in locations where flooding of an LWSC would deprive dwelling places of emergency ground access.

Cardiovascular effects in patrol officers are associated with fine particulate matter from brake wear and engine emissions

Background: Exposure to fine particulate matter air pollutants (PM2.5) affects heart rate variability parameters, and levels of serum proteins associated with inflammation, hemostasis and thrombosis. This study investigated sources potentially responsible for cardiovascular and hematological effects in highway patrol troopers. Results: Nine healthy young non-smoking male troopers working from 3 PM to midnight were studied on four consecutive days during their shift and the following night. Sources of in-vehicle PM2.5 were identified with variance-maximizing rotational principal factor analysis of PM2.5-components and associated pollutants. Two source models were calculated. Sources of in-vehicle PM2.5 identified were 1) crustal material, 2) wear of steel automotive components, 3) gasoline combustion, 4) speed-changing traffic with engine emissions and brake wear. In one model, sources 1 and 2 collapsed to a single source. Source factors scores were compared to cardiac and blood parameters measured ten and fifteen hours, respectively, after each shift. The "speed-change" factor was significantly associated with mean heart cycle length (MCL, +7% per standard deviation increase in the factor score), heart rate variability (+16%), supraventricular ectopic beats (+39%), % neutrophils (+7%), % lymphocytes (-10%), red blood cell volume MCV (+1%), von Willebrand Factor (+9%), blood urea nitrogen (+7%), and protein C (-11%). The "crustal" factor (but not the "collapsed" source) was associated with MCL (+3%) and serum uric acid concentrations (+5%). Controlling for potential confounders had little influence on the effect estimates. Conclusion: PM2.5 originating from speed-changing traffic modulates the autonomic control of the heart rhythm, increases the frequency of premature supraventricular beats and elicits proinflammatory and pro-thrombotic responses in healthy young men. [Authors]