Demonstration of Load Rating Capabilities through Physical Load Testing: Sioux County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Sioux County Bridge (FHWA #308730), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Ida County Bridge (FHWA #186070) and the Johnson County Bridge (FHWA #205750). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing: Ida County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Ida County Bridge (FHWA #186070), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Sioux County Bridge (FHWA #308730) and the Johnson County Bridge (FHWA #205750). A tech brief provides overall information about the project.

Demonstration of Load Rating Capabilities through Physical Load Testing: Johnson County Bridge Case Study, RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. This report documents one of three bridges inspected, load tested, and load rated as part of the project, the Johnson County Bridge (FHWA #205750), including testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. Two parallel reports document the testing and load rating of the Sioux County Bridge (FHWA #308730) and the Ida County Bridge (FHWA #186070). A tech brief provides overall information about the project.

Pilot Project - Demonstration of Load Rating Capabilities through Physical Load Testing: Tech Transfer Summary, RB32-013, 2013

This project demonstrated the capabilities for load testing bridges in Iowa, developed and presented a webinar to local and state engineers, and produced a spreadsheet and benefit evaluation matrix that others can use to preliminarily assess where bridge testing may be economically feasible given truck traffic and detour lengths.

Demonstration of Load Rating Capabilities through Physical Load Testing (4 vol), RB32-013, 2013

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of performing such testing, and perform outreach to local, state, and national engineers on the topic of bridge load testing and rating. The three final reports document one each of three bridges inspected, load tested, and load rated as part of the project. The bridges include the Sioux County Bridge (FHWA #308730), the Ida County Bridge (FHWA #186070), and the Johnson County Bridge (FHWA #205750). Actions included testing procedures and performance of the bridge under static loading along with the calculated load rating from the field-calibrated analytical model. A Tech Transfer Summary provides overall information about the project.

Determination of entrance loss coefficients for pre-cast reinforced Concrete Box Culverts, December 2012

There is an increased interest in constructing Pre-Cast (PC) Twin and Triple Reinforced Concrete Box (RCB) culverts in Iowa due to the efficiency associated with their production in controlled environment and decrease of the construction time at the culvert sites. The design of the multi-barrel PC culverts is, however, based on guidelines for single-barrel cast-inplace (CIP) culverts despite that the PC and CIP culverts have different geometry. There is scarce information for multiplebarrel RCB culverts in general and even fewer on culverts with straight wingwalls as those designed by Iowa DOT. Overall, the transition from CIP to PC culverts requires additional information for improving the design specifications currently in use. Motivated by the need to fill these gaps, an experimental study was undertaken by IIHR-Hydroscience & Engineering. The goals of the study are to document flow performance curves and head losses at the culvert entrance for a various culvert geometry, flow conditions, and settings. The tests included single-, double- and triple-barrel PC and CIP culverts with two span-to-rise ratios set on mild and steep slopes. The tests also included optimization of the culvert geometry entrance by considering various configurations for the top bevel. The overall conclusion of the study is that by and large the current Iowa DOT design specifications for CIP culverts can be used for multi-barrel PC culvert design. For unsubmerged flow conditions the difference in the hydraulic performance curves and headloss coefficients for PC and CIP culverts are within the experimental uncertainty. Larger differences (specified by the study) are found for submerged conditions when the flow is increasingly constricted at the entrance in the culvert. The observed differentiation is less important for multi-barrel culverts as the influence of the wingwalls decreases with the increase of the number of barrels.

Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide.

AIMS/HYPOTHESIS: Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide. METHODS: Sixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n = 8) or EX (n = 8). Insulin sensitivity was determined using hyperinsulinaemic-euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry. RESULTS: Insulin sensitivity was improved with DIWL (20.6 ± 4.7%) and EX (19.2 ± 12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p < 0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (-12.4 ± 14.6%) and EX (-40.9 ± 12.0%). Ceramide decreased with EX (-33.7 ± 11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (-19.5 ± 8.5%, p < 0.05), but increased with EX (19.6 ± 7.4%, p < 0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions. CONCLUSIONS/INTERPRETATION: Diet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00766298.

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.

Physical activity in free-living, overweight white and black women: divergent responses by race to diet-induced weight loss.

BACKGROUND: Black women are at greater risk of obesity than are white women, perhaps because of their lower levels of physical activity. OBJECTIVE: We compared free-living activity energy expenditure (AEE) in sedentary white and black women (in overweight and normal-weight states) and in never-overweight control subjects. DESIGN: Subjects included 46 women (23 white, 23 black) studied while overweight and after reaching a normal weight and 38 female control subjects (23 white, 15 black). Diet, without exercise training, resulted in a mean weight loss of 13 kg and a body mass index (in kg/m(2)) < 25. Body composition, sleeping energy expenditure, free-living total energy expenditure, and the energy cost of activity and aerobic capacity were assessed before and after weight loss under 4-wk, diet-controlled, weight-stable conditions and in the control subjects. AEE was defined as above-sleep energy expenditure. RESULTS: No significant racial differences in body composition, before or after weight loss, were found. After weight loss, AEE and aerobic capacity increased in the white women and decreased in the black women (P < 0.05 and P < 0.02, respectively). After weight loss, but not before, the white women had a significantly higher mean AEE than did the black women (2448 +/- 979 and 1728 +/- 1373 kJ/d, respectively; P < 0.05), approximating AEEs in the white (2314 +/- 1105) and black (2310 +/- 1251) control subjects. CONCLUSIONS: Relative to the responses of the white women to diet-induced weight loss, the black women became less fit and less physically active. Induction of a normal body weight in overweight black women appeared to produce a more obesity-prone state, favoring weight relapse.

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.

Efficacy, tolerability and risk factors for virological failure of darunavir-based therapy for treatment-experienced HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice. METHODS: We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors. We followed these patients for up to 72 weeks, assessed virological failure using different loss of virological response algorithms and evaluated risk factors for virological failure using a Bayesian method to fit discrete Cox proportional hazard models. RESULTS: Among 130 treatment-experienced patients starting darunavir, the median age was 47 years, the median duration of HIV infection was 16 years, and 82% received mono or dual antiretroviral therapy before starting highly active antiretroviral therapy. During a median patient follow-up period of 45 weeks, 17% of patients stopped taking darunavir after a median exposure of 20 weeks. In patients followed beyond 48 weeks, the rate of virological failure at 48 weeks was at most 20%. Virological failure was more likely where patients had previously failed on both amprenavir and saquinavir and as the number of previously failed PI regimens increased. CONCLUSIONS: As a component of therapy for treatment-experienced patients, darunavir can achieve a similar efficacy and tolerability in clinical practice to that seen in clinical trials. Clinicians should consider whether a patient has failed on both amprenavir and saquinavir and the number of failed PI regimens before prescribing darunavir.

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.

Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

BACKGROUND: The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth. METHODOLOGY AND PRINCIPAL FINDINGS: To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD), characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP), a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD) characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia. SIGNIFICANCE: Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

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.