Field Evaluation of Elliptical Fiber Reinforced Polymer Dowel Performance, June 2003

Fiber composite materials (FRP) are making an entry into the construction market in both buildings and pavements. The application to pavements comes in the form of joint reinforcement (dowels and tie bars) to date. FRP resistance to salt corrosion in dowels has made it an alternative to standard epoxy coated dowels for pavements. Iowa State University has completed a large amount of laboratory research into the determination of diameter, spacing, and durability of FRP dowels. This report documents the installation of a series of FRP elliptical-shaped dowel joints (including instrumented units) in a field situation and the beginning of a two-year study to compare laboratory results to in-service pavements. Ten joints were constructed for each of three dowel spacings of 10, 12, and 15 inches ( 254, 305, and 381 mm) with one instrumented joint in each test section. The instrumented bars will be load tested with a loaded truck and FWD testing.

Mechanical ventilation and clinical practice heterogeneity in intensive care units: a multicenter case-vignette study.

BACKGROUND: Observational studies on mechanical ventilation (MV) show practice variations across ICUs. We sought to determine, with a case-vignette study, the heterogeneity of processes of care in ICUs focusing on mechanical ventilation procedures, and whether organizational patterns or physician characteristics influence practice variations. METHODS: We conducted a cross-sectional multicenter study using the case-vignette methodology. Descriptive analyses were calculated for each organizational pattern and respondent characteristics. An Index of Qualitative Variation (IQV, from 0, no heterogeneity, to a maximum of 1) was calculated. RESULTS: Forty ICUs from France (N = 33) and Switzerland (N = 7) participated; 396 physicians answered our case-vignettes. There was major heterogeneity of management processes related to MV within and across centers (mean IQV per center 0.51, SD 0.09). We observed the lowest variability (mean IQV per question < 0.4) for questions related to intubation procedure, ventilation of acute respiratory distress syndrome and the use of the semirecumbent position. We observed a high variability (mean IQV per question > 0.6) for questions related to management of endotracheal tube or suctioning, management of sedation and analgesia, and respect of autonomy. Heterogeneity was independent of respondent characteristics and of the presence of written procedures. There was a correlation between the processes associated with the highest variability (mean IQV per question > 0.6) and the annual volume of ICU admission (r = 0.32 (0.01 to 0.58)) and MV (r = 0.38 (0.07 to 0.63)). Within ICUs there was a large heterogeneity regarding knowledge of a local written procedure. CONCLUSIONS: Large clinical practice variations were found among ICUs. High volume centers were more likely to have heterogeneous practices. The presence of a local written procedure or respondent characteristics did not influence practice variation.

Population PK-guided simulation study in children exposed to drugs in human milk

Risks of significant infant drug exposure through human milk arepoorly defined due to lack of large-scale PK data. We propose to useBayesian approach based on population PK (popPK)-guided modelingand simulation for risk prediction. As a proof-of-principle study, weexploited fluoxetine milk concentration data from 25 women. popPKparameters including milk-to-plasma ratio (MP ratio) were estimatedfrom the best model. The dose of fluoxetine the breastfed infant wouldreceive through mother's milk, and infant plasma concentrations wereestimated from 1000 simulated mother-infant pairs, using randomassignment of feeding times and milk volume. A conservative estimateof CYP2D6 activity of 20% of the allometrically-adjusted adult valuewas assumed. Derived model parameters, including MP ratio were consistentwith those reported in the literature. Visual predictive check andother model diagnostics showed no signs of model misspecifications.The model simulation predicted that infant exposure levels to fluoxetinevia mother's milk were below 10% of weight-adjusted maternal therapeuticdoses in >99% of simulated infants. Predicted median ratio ofinfant-mother serum levels at steady state was 0.093 (range 0.033-0.31),consistent with literature reported values (mean=0.07; range 0-0.59).Predicted incidence of relatively high infant-mother ratio (>0.2) ofsteady-state serum fluoxetine concentrations was <1.3%. Overall, ourpredictions are consistent with clinical observations. Our approach maybe valid for other drugs, allowing in silico prediction of infant drugexposure risks through human milk. We will discuss application of thisapproach to another drug used in lactating women.

Validation of diagnosis criteria for acquired sensory neuronopathy. a francophone multicenter study

Recently published criteria using clinical (ataxia or asymmetrical distribution at onset or full development, and sensory loss not restricted to the lower limbs) and electrophysiological items (less than two abnormal lower limb motor nerves and at least an abolished SAP or three SAP below 30% of lower limit of normal in the upper limbs) were sensitive and specific for the diagnosis of sensory neuronopathy (SNN) (Camdessanche et al., Brain, 2009). However, these criteria need to be validated on a large multicenter population. For this, a database collecting cases from fifteen Reference Centers for Neuromuscular diseases in France and Switzerland is currently developed. So far, data from 120 patients with clinically pure sensory neuropathy have been collected. Cases were classified independently from the evaluated criteria as SNN (53), non-SNN (46) or suspected SNN (21) according to the expert's diagnosis. Using the criteria, SNN was possible in 83% (44/53), 23.9% (11/46) and 71.4% (15/21) of cases, respectively. In the non-SSN group, half of the patients with a diagnosis of possible SSN had an ataxic form of inflammatory demyelinating neuropathy. In the SNN group, half of those not retained as possible SNN had CANOMAD, paraneoplasia, or B12 deficiency. In a second step, after application of the items necessary to reach the level of probable SNN (no biological or electrophysiological abnormalities excluding SNN; presence of onconeural antibody, cisplatin treatment, Sj ¨ ogren's syndrome or spinal cord MRI high signal in the posterior column), a final diagnosis of possible or probable SNN was obtained in, respectively, 90.6% (48/53), 8.8% (4/45), and 71.4% (15/21) of patients in the three groups. Among the 5 patients with a final non-SNN but initial SNN diagnosis, 3 had motor conduction abnormalities (one with CANOMAD) and among the 4 patients with a final SNN but initial non-SSN diagnosis, one had anti-Hu antibody and one was discussed as a possible ataxic CIDP. These preliminary results confirm the sensitivity and specificity of the proposed criteria for the diagnosis of SNN.

Iowa Gender Wage Study, 1999

In 1993, Iowa Workforce Development (then the Department of Employment Services) conducted a survey to determine if there was a gender gap in wages paid. The results of that survey indicated that women were paid 68 cents per dollar paid to males. We felt a need to determine if this relationship of wages paid to each gender has changed since the 1993 study. In 1999, the Commission on the Status of Women requested that Iowa Workforce Development conduct research to update the 1993 information. A survey, cosponsored by the Commission on the Status of Women and Iowa Workforce Development, was conducted in 1999. The results of the survey showed that women earned 73 percent of what men earned when both jobs were considered. (The survey asked respondents to provide information on a primary job and a secondary job.) The ratio for the primary job was 72 percent, while the ratio for the secondary job was 85 percent. Additional survey results detail the types of jobs respondents had, the types of companies for which they worked and the education and experience levels. All of these characteristics can contribute to these ratios. While the large influx of women into the labor force may be over, it is still important to look at such information to determine if future action is needed. We present these results with that goal in mind. We are indebted to those Iowans, female and male, who voluntarily completed the survey. This study was completed under the general direction of Judy Erickson. The report was written by Shazada Khan, Teresa Wageman, Ann Wagner, and Yvonne Younes with administrative and technical assistance from Michael Blank, Margaret Lee and Gary Wilson. The Iowa State University Statistical Lab provided sampling advice, data entry and coding and data analysis.

Epidemiology of incident heart failure in a contemporary elderly cohort: the health, aging, and body composition study.

BACKGROUND: The race- and sex-specific epidemiology of incident heart failure (HF) among a contemporary elderly cohort are not well described. METHODS: We studied 2934 participants without HF enrolled in the Health, Aging, and Body Composition Study (mean [SD] age, 73.6 [2.9] years; 47.9% men; 58.6% white; and 41.4% black) and assessed the incidence of HF, population-attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF. RESULTS: During a median follow-up of 7.1 years, 258 participants (8.8%) developed HF (13.6 cases per 1000 person-years; 95% confidence interval, 12.1-15.4). Men and black participants were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (PAR, 23.9% for white participants and 29.5% for black participants) and uncontrolled blood pressure (PAR, 21.3% for white participants and 30.1% for black participants) carried the highest PAR in both races. Among black participants, 6 of 8 risk factors assessed (smoking, increased heart rate, coronary heart disease, left ventricular hypertrophy, uncontrolled blood pressure, and reduced glomerular filtration rate) had more than 5% higher PAR compared with that among white participants, leading to a higher overall proportion of HF attributable to modifiable risk factors in black participants vs white participants (67.8% vs 48.9%). Participants who developed HF had higher annual mortality (18.0% vs 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher among black participants (62.1 vs 30.3 hospitalizations per 100 person-years, P < .001). CONCLUSIONS: Incident HF is common in older persons; a large proportion of HF risk is attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be considered in prevention and treatment efforts.

An evaluation of new parsimony-based versus parametric inference methods in biogeography: a case study using the globally distributed plant family Sapindaceae

Aim  Recently developed parametric methods in historical biogeography allow researchers to integrate temporal and palaeogeographical information into the reconstruction of biogeographical scenarios, thus overcoming a known bias of parsimony-based approaches. Here, we compare a parametric method, dispersal-extinction-cladogenesis (DEC), against a parsimony-based method, dispersal-vicariance analysis (DIVA), which does not incorporate branch lengths but accounts for phylogenetic uncertainty through a Bayesian empirical approach (Bayes-DIVA). We analyse the benefits and limitations of each method using the cosmopolitan plant family Sapindaceae as a case study.Location  World-wide.Methods  Phylogenetic relationships were estimated by Bayesian inference on a large dataset representing generic diversity within Sapindaceae. Lineage divergence times were estimated by penalized likelihood over a sample of trees from the posterior distribution of the phylogeny to account for dating uncertainty in biogeographical reconstructions. We compared biogeographical scenarios between Bayes-DIVA and two different DEC models: one with no geological constraints and another that employed a stratified palaeogeographical model in which dispersal rates were scaled according to area connectivity across four time slices, reflecting the changing continental configuration over the last 110 million years.Results  Despite differences in the underlying biogeographical model, Bayes-DIVA and DEC inferred similar biogeographical scenarios. The main differences were: (1) in the timing of dispersal events - which in Bayes-DIVA sometimes conflicts with palaeogeographical information, and (2) in the lower frequency of terminal dispersal events inferred by DEC. Uncertainty in divergence time estimations influenced both the inference of ancestral ranges and the decisiveness with which an area can be assigned to a node.Main conclusions  By considering lineage divergence times, the DEC method gives more accurate reconstructions that are in agreement with palaeogeographical evidence. In contrast, Bayes-DIVA showed the highest decisiveness in unequivocally reconstructing ancestral ranges, probably reflecting its ability to integrate phylogenetic uncertainty. Care should be taken in defining the palaeogeographical model in DEC because of the possibility of overestimating the frequency of extinction events, or of inferring ancestral ranges that are outside the extant species ranges, owing to dispersal constraints enforced by the model. The wide-spanning spatial and temporal model proposed here could prove useful for testing large-scale biogeographical patterns in plants.

Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.

During pregnancy the plasma concentration of two different inhibitors of plasminogen activators (PAIs) increases. The only one found in the plasma of nonpregnant women (PAI1) is immunologically related to a PAI of endothelial cells; its plasma activity, as deduced from the inhibition of single-chain tissue-type plasminogen activator (t-PA), increased from 3.4 +/- 2.3 U/mL (mean +/- 95% confidence limits) in the plasma of nonpregnant women to 29 +/- 7 U/mL at term, and its antigen level, measured by a radioimmunoassay, increased from 54 +/- 17 ng/mL to 144 +/- 25 ng/mL. In pregnancy plasma a second PAI (PAI 2) related to a PAI found in placenta extracts was observed. Its level, quantified with a radioimmunoassay, increased from below the detection limit (approximately 10 ng/mL) in normal plasma to 260 ng/mL at term. One hour after delivery, PAI 1 activities and antigen decreased sharply, but the PAI 2 antigen levels remained constant. Three days later, the PAI 1 antigen levels had fallen to normal levels, but the PAI 2 antigen levels were still at least eightfold above the nonpregnant values. During pregnancy, the t-PA and prourokinase (u-PA) antigen concentrations increased 50% and 200%, respectively, whereas the plasminogen and alpha 2-antiplasmin levels remained constant. Despite the large variations in the levels of PAs and PAIs, the overall fibrinolytic activity as measured in diluted plasma by a radioiodinated fibrin plate assay did not change significantly. Just after delivery, a great increase in the t-PA antigen levels was observed. Three to five days after delivery most parameters of the fibrinolytic system were normal again. Our results demonstrate that during pregnancy and in the puerperium profound alterations of the fibrinolytic system occur that are characterized by increases in PAs and their inhibitors, but these alterations do not affect the overall fibrinolytic activity.

Study of protein complexes

Summary : A lot of information can be obtained on proteins when proteomics methods are used. In our study, we aimed to characterize complexes containing pro-apoptotic proteins by different proteomics methods and finally focused on PIDD (p53-induced protein with a death domain), for which the most interesting results were obtained. PIDD has been shown to function as a molecular switch between genotoxic stress-induced apoptotis and genotoxic stress-induced cell survival through NF-κB activation. To exert these two functions, PIDD forms alternate complexes respectively with caspase2 and CRADD on one hand and RIP 1 and NEMO on the other hand. The first part of our study focuses on the processing of PIDD. PIDD full length (FL) is constitutively cleaved into three fragments, an N-terminal one (PIDD-N) and two fragments containing the C-terminus (PIDD-C and PIDD-CC). Localization of the two PIDD cleavage sites by mass spectrometry (MS) allowed to understand that PIDD is probably not cleaved by proteases but is subject to protein (self-)splicing and also to map the PIDD-N, PIDD-C and PIDD-CC fragments exactly. Further characterization of these three fragments by Tinel et al. (Tinel et al., 2007) showed that PIDD-C is involved in activation of an apoptotic pathway while PIDD-CC is involved in NF-κB activation. We also found that PIDD is subject to proline-directed phosphorylation at two serine residues in PIDD-N, the regulatory fragment of PIDD. The second part of the study aimed at identifying by proteomics techniques proteins that co-purify with PIDD and therefore are putative cellular interaction partners. In this respect we analyzed samples obtained in different conditions or with different PIDD constructs corresponding to processed fragments. This allowed us to identify a large number of potential interactors for PIDD. For example, by comparing data obtained from PIDD-C and PIDD-FL affinity purifications, we found that the Hsp90 chaperone system interacts strongly with PIDD-N. In the third part of this study, we developed methods to selectively and rapidly quantify by MS proteins of interest in PIDD affinity purifications or negative controls. Using these tools we detected significant changes in PIDD-FL-copurifying proteins treated by heat shock. Overall, our studies provide informative data on the processing of PIDD and its possible involvement in several molecular pathways.

Metastatic tumors to the colon and rectum: a multi-institutional study.

Context.-Unlike the small bowel, the colorectal mucosa is seldom the site of metastatic disease. Objective.-To determine the incidence of truly colorectal metastases, and subsequent clinicopathologic findings, in a substantial colorectal cancer population collected from 7 European centers. Design.-During the last decade, 10 365 patients were identified as having colorectal malignant tumors, other than systemic diseases. Data collected included patient demographics, clinical symptoms, treatment, the presence of metastases in other sites, disease-free interval, follow-up, and overall survival. All secondary tumors resulting from direct invasion from malignant tumors of the contiguous organs were excluded, as well as those resulting from lymph node metastases or peritoneal seeding. Results.-Only 35 patients were included (10 men) with a median age of 59 years. They presented with obstruction, bleeding, abdominal pain, or perforation. The leading source of metastases was the breast, followed by melanoma. Metastases were synchronous in 3 cases. The mean disease-free interval for the remaining cases was 6.61 years. Surgical resection was performed in 28 cases. Follow-up was available for 26 patients; all had died, with a mean survival time of 10.67 months (range, 1-41 months). Conclusions.-Colorectal metastases are exceptional (0.338%) with the breast as a leading source of metastases; they still represent a late stage of disease and reflect a poor prognosis. Therefore, the pathologist should be alert for the possibility of secondary tumors when studying large bowel biopsies. Any therapy is usually palliative, but our results suggest that prolonged survival after surgery and complementary therapy can be obtained in some patients.

Maternal side-effects after multiple courses of antenatal corticosteroids (MACS): the three-month follow-up of women in the randomized controlled trial of MACS for preterm birth study.

OBJECTIVE: A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression. The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. METHODS: Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale. Women were also asked to evaluate their study participation. RESULTS: Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. CONCLUSION: In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Association study of 182 candidate genes in anorexia nervosa.

We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN.

Tools and techniques to study ligand-receptor interactions and receptor activation by TNF superfamily members.

Ligands and receptors of the TNF superfamily are therapeutically relevant targets in a wide range of human diseases. This chapter describes assays based on ELISA, immunoprecipitation, FACS, and reporter cell lines to monitor interactions of tagged receptors and ligands in both soluble and membrane-bound forms using unified detection techniques. A reporter cell assay that is sensitive to ligand oligomerization can identify ligands with high probability of being active on endogenous receptors. Several assays are also suitable to measure the activity of agonist or antagonist antibodies, or to detect interactions with proteoglycans. Finally, self-interaction of membrane-bound receptors can be evidenced using a FRET-based assay. This panel of methods provides a large degree of flexibility to address questions related to the specificity, activation, or inhibition of TNF-TNF receptor interactions in independent assay systems, but does not substitute for further tests in physiologically relevant conditions.

Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study.

BACKGROUND: Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability. METHODS: All medications were prospectively recorded in 1,497 ART-treated patients and screened for PDDIs using a customized version of the Liverpool drug interactions database. RESULTS: Overall, 68% (1,013/1,497) of patients had a comedication and 40% (599/1,497) had > or = 1 PDDI. Among patients with comedication, 2% (21/1,013) had red-flag interactions (contraindicated) and 59% (597/1,013) had orange-flag interactions (potential dose adjustment and/or close monitoring required). The latter involved mainly central nervous system drugs (49%), cardiovascular drugs (34%) and methadone (19%). In the multivariate analysis, factors associated with having a comedication were advanced age, female gender, obesity and HCV infection. Independent risk factors for PDDIs were regimens combining protease inhibitors and non-nucleoside reverse transcriptase inhibitors (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.44-6.48), > or = 2 comedications (OR 1.89, 95% CI 1.32-2.70), current illicit drug use (OR 2.00, 95% CI 1.29-3.10) and patients with HCV infection (OR 1.74, 95% CI 1.19-2.56). Viral response was similar in patients with and without PDDIs (84.5% versus 86.4%; P=0.386). During follow-up, ART was modified in 134 patients with comedication regardless of the presence of PDDIs (P=0.524). CONCLUSIONS: PDDIs increase with complex ART and comorbidities. No adverse effect was noted on ART efficacy or tolerability; however, most PDDIs affected comedication but were manageable through dose adjustment or monitoring.

Differential DNA extraction of challenging simulated sexual assault samples: a Swiss collaborative study.

ABSTRACT: In sexual assault cases, autosomal DNA analysis of gynecological swabs is a challenge, as the presence of a large quantity of female material may prevent the detection of the male DNA. A solution to this problem is differential DNA extraction, but as there are different protocols, it was decided to test their efficiency on simulated casework samples. Four difficult samples were sent to the nine Swiss laboratories active in the forensic genetics. They used their routine protocols to separate the epithelial cell fraction, enriched with the non-sperm DNA, from the sperm fraction. DNA extracts were then sent to the organizing laboratory for analysis. Estimates of male to female DNA ratio without differential DNA extraction ranged from 1:38 to 1:339, depending on the semen used to prepare the samples. After differential DNA extraction, most of the ratios ranged from 1:12 to 9:1, allowing the detection of the male DNA. Compared to direct DNA extraction, cell separation resulted in losses of 94-98% of the male DNA. As expected, more male DNA was generally present in the sperm than in the epithelial cell fraction. However, for about 30% of the samples, the reverse trend was observed. The recovery of male and female DNA was highly variable depending on the laboratories. Experimental design similar to the one used in this study may help for local protocol testing and improvement.