Changes in Aortic Pulse Wave Velocity in Hypertensive Postmenopausal Women: Comparison Between a Calcium Channel Blocker vs Angiotensin Receptor Blocker Regimen.

J Clin Hypertens (Greenwich). 2012;14:773-778. ©2012 Wiley Periodicals, Inc. Postmenopausal women are at greater risk for hypertension-related cardiovascular disease. Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension. This randomized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness. Overall, 125 postmenopausal hypertensive women (age, 61.4±6 years; systolic blood pressure/diastolic blood pressure [SBP/DBP], 158±11/92±9 mm Hg) were randomized to valsartan 320 mg±hydrochlorothiazide (HCTZ) (n=63) or amlodipine 10 mg±HCTZ (n=62). The primary outcome was carotid-to-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Both treatments lowered peripheral blood pressure (BP) (-22.9/-10.9 mm Hg for valsartan and -25.2/-11.7 mm Hg for amlodipine, P=not significant) and central BP (-15.7/-7.6 mm Hg for valsartan and -19.2/-10.3 mm Hg for amlodipine, P<.05 for central DBP). Both treatments similarly reduced the carotid-femoral PWV (-1.9 vs -1.7 m/s; P=not significant). Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group (77% vs 14%, P<.001). BP lowering in postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement. Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering, suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects.

Shear thinning and thixotropy of HMHEC and HEC water solutions

Steady state viscosity and thixotropy of hydrophobically modified hydroxyethyl cellulose HMHEC and nonassociative cellulose water solutions are studied. Although all the samples are shear thinning, only the HMHEC is thixotropic, since the migration of hydrophobes to micelles is controlled by diffusion. The Cross model fits steady state curves. The Mewis model, a phenomenological model that proposes that the rate of change of viscosity when the shear rate is suddenly changed is related to the difference between the steady state and current values of viscosity raised to an exponent, fits structure construction experiments when the exponent, n, is estimated to be around 2. The Newtonian assumption used by Mewis cannot be used here, however. This seems to be related to the fact that the thickening is due to bridged micelle formation, which is a slow process, and also to topological constraints and entanglements, which are rapid processes. The kinetic parameter was redefined to kn in order to make it independent of initial conditions. So, kn depends only on how the shear affects the structure. kn reaches a plateau at shear rates too low to produce structure destruction and decreases at higher shear rates.

Innovative Solutions for Slope Stability Reinforcement and Characterization: Vol. I, TR-489, 2005

Soil slope instability concerning highway infrastructure is an ongoing problem in Iowa, as slope failures endanger public safety and continue to result in costly repair work. Characterization of slope failures is complicated, because the factors affecting slope stability can be difficult to discern and measure, particularly soil shear strength parameters. While in the past extensive research has been conducted on slope stability investigations and analysis, this research consists of field investigations addressing both the characterization and reinforcement of such slope failures. The current research focuses on applying an infrequently-used testing technique comprised of the Borehole Shear Test (BST). This in-situ test rapidly provides effective (i.e., drained) shear strength parameter values of soil. Using the BST device, fifteen Iowa slopes (fourteen failures and one proposed slope) were investigated and documented. Particular attention was paid to highly weathered shale and glacial till soil deposits, which have both been associated with slope failures in the southern Iowa drift region. Conventional laboratory tests including direct shear tests, triaxial compression tests, and ring shear tests were also performed on undisturbed and reconstituted soil samples to supplement BST results. The shear strength measurements were incorporated into complete evaluations of slope stability using both limit equilibrium and probabilistic analyses. The research methods and findings of these investigations are summarized in Volume 1 of this report. Research details of the independent characterization and reinforcement investigations are provided in Volumes 2 and 3, respectively. Combined, the field investigations offer guidance on identifying the factors that affect slope stability at a particular location and also on designing slope reinforcement using pile elements for cases where remedial measures are necessary. The research findings are expected to benefit civil and geotechnical engineers of government transportation agencies, consultants, and contractors dealing with slope stability, slope remediation, and geotechnical testing in Iowa.

Innovative Solutions for Slope Stability Reinforcement and Characterization: Vol. II, TR-489, 2005

Soil slope instability concerning highway infrastructure is an ongoing problem in Iowa, as slope failures endanger public safety and continue to result in costly repair work. While in the past extensive research has been conducted on slope stability investigations and analysis, this current research study consists of field investigations addressing both the characterization and reinforcement of such slope failures. While Volume I summarizes the research methods and findings of this study, Volume II provides procedural details for incorporating an infrequently-used testing technique, borehole shear tests, into practice. Fifteen slopes along Iowa highways were investigated, including thirteen slides (failed slopes), one unfailed slope, and one proposed embankment slope (the Sugar Creek Project). The slopes are mainly comprised of either clay shale or glacial till, and are generally gentle and of small scale, with slope angle ranging from 11 deg to 23 deg and height ranging from 6 to 23 m. Extensive field investigations and laboratory tests were performed for each slope. Field investigations included survey of slope geometry, borehole drilling, soil sampling, in-situ Borehole Shear Testing (BST) and ground water table measurement. Laboratory investigations mainly comprised of ring shear tests, soil basic property tests (grain size analysis and Atterberg limits test), mineralogy analyses, soil classifications, and natural water contents and density measurements on the representative soil samples from each slope. Extensive direct shear tests and a few triaxial compression tests and unconfined compression tests were also performed on undisturbed soil samples for the Sugar Creek Project. Based on the results of field and lab investigations, slope stability analysis was performed on each of the slopes to determine the possible factors resulting in the slope failures or to evaluate the potential slope instabilities using limit equilibrium methods. Deterministic slope analyses were performed for all the slopes. Probabilistic slope analysis and sensitivity study were also performed for the slope of the Sugar Creek Project. Results indicate that while the in-situ test rapidly provides effective shear strength parameters of soils, some training may be required for effective and appropriate use of the BST. Also, it is primarily intended to test cohesive soils and can produce erroneous results in gravelly soils. Additionally, the quality of boreholes affects test results, and disturbance to borehole walls should be minimized before test performance. A final limitation of widespread borehole shear testing may be its limited availability, as only about four to six test devices are currently being used in Iowa. Based on the data gathered in the field testing, reinforcement investigations are continued in Volume III.

Innovative Solutions for Slope Stability Reinforcement and Characterization: Vol. III, TR-489, 2005

Soil slope instability concerning highway infrastructure is an ongoing problem in Iowa, as slope failures endanger public safety and continue to result in costly repair work. Volume I of this current study summarizes research methods and findings, while Volume II provides procedural details for incorporating into practice an infrequently-used testing technique–borehole shear tests. Volume III of this study of field investigation of fifteen slopes in Iowa demonstrates through further experimental testing how lateral forces develop along stabilizing piles to resist slope movements. Results establish the feasibility of an alternative stabilization approach utilizing small-diameter pile elements. Also, a step-by-step procedure that can be used by both state and county transportation agencies to design slope reinforcement using slender piles is documented. Initial evidence of the efficiency and cost-effectiveness of stabilizing nuisance slope failures with grouted micropiles is presented. Employment of the remediation alternative is deemed more appropriate for stabilizing shallow slope failures. Overall, work accomplished in this research study included completing a comprehensive literature review on the state of the knowledge of slope stability and slope stabilization, the preparation and performance of fourteen full-scale pile load tests, the analysis of load test results, and the documentation of a design methodology for implementing the technology into current practices of slope stabilization. Recommendations for further research include monitoring pilot studies of slope reinforcement with grouted micropiles, supplementary experimental studies, and advanced numerical studies.

Mobilizing and evaluating anticancer T cells: pitfalls and solutions.

Immunotherapy is a promising means to fight cancer, prompting a steady increase in clinical trials and correlative laboratory studies in this field. As antitumor T cells play central roles in immunity against malignant diseases, most immunotherapeutic protocols aim to induce and/or strengthen their function. Various treatment strategies have elicited encouraging clinical responses; however, major challenges have been uncovered that should be addressed in order to fully exploit the potential of immunotherapy. Here, we outline pitfalls for the mobilization of antitumor T cells and offer solutions to improve their therapeutic efficacy. We provide a critical perspective on the main methodologies used to characterize T-cell responses to cancer therapies, with a focus on discrepancies between T-cell attributes measured in vitro and protective responses in vivo. This review altogether provides recommendations to optimize the design of future clinical trials and highlights important considerations for the proficient analysis of clinical specimens available for research.

Comparison of the power spectral changes of the voluntary surface electromyogram and M wave during intermittent maximal voluntary contractions.

INTRODUCTION: To compare the power spectral changes of the voluntary surface electromyogram (sEMG) and of the compound action potential (M wave) in the vastus medialis and vastus lateralis muscles during fatiguing contractions. METHODS: Interference sEMG and force were recorded during 48 intermittent 3-s isometric maximal voluntary contractions (MVC) from 13 young, healthy subjects. M waves and twitches were evoked using supramaximal femoral nerve stimulation between the successive MVCs. Mean frequency (F mean), and median frequency were calculated from the sEMG and M waves. Muscle fiber conduction velocity (MFCV) was computed by cross-correlation. RESULTS: The power spectral shift to lower frequencies was significantly greater for the voluntary sEMG than for the M waves (P < 0.05). Over the fatiguing protocol, the overall average decrease in MFCV (~25 %) was comparable to that of sEMG F mean (~22 %), but significantly greater than that of M-wave F mean (~9 %) (P < 0.001). The mean decline in MFCV was highly correlated with the mean decreases in both sEMG and M-wave F mean. CONCLUSIONS: The present findings indicated that, as fatigue progressed, central mechanisms could enhance the relative weight of the low-frequency components of the voluntary sEMG power spectrum, and/or the end-of-fiber (non-propagating) components could reduce the sensitivity of the M-wave spectrum to changes in conduction velocity.

3D solutions in transmission electron (Cryo) -microscopy in biology

One of the main problems in transmission electron microscopy in thebiological field is the tri-dimensionality. This article explains the technicalprocedures and requirements to prepare biological specimens preserving themclosest to their native state to perform 3D reconstruction of the macromolecularcomplexes and cellular structures in their natural environment.

Development of Asphalt Dynamic Modulus Master Curve Using Falling Weight Deflectometer Measurements, TR-659

The asphalt concrete (AC) dynamic modulus (|E*|) is a key design parameter in mechanistic-based pavement design methodologies such as the American Association of State Highway and Transportation Officials (AASHTO) MEPDG/Pavement-ME Design. The objective of this feasibility study was to develop frameworks for predicting the AC |E*| master curve from falling weight deflectometer (FWD) deflection-time history data collected by the Iowa Department of Transportation (Iowa DOT). A neural networks (NN) methodology was developed based on a synthetically generated viscoelastic forward solutions database to predict AC relaxation modulus (E(t)) master curve coefficients from FWD deflection-time history data. According to the theory of viscoelasticity, if AC relaxation modulus, E(t), is known, |E*| can be calculated (and vice versa) through numerical inter-conversion procedures. Several case studies focusing on full-depth AC pavements were conducted to isolate potential backcalculation issues that are only related to the modulus master curve of the AC layer. For the proof-of-concept demonstration, a comprehensive full-depth AC analysis was carried out through 10,000 batch simulations using a viscoelastic forward analysis program. Anomalies were detected in the comprehensive raw synthetic database and were eliminated through imposition of certain constraints involving the sigmoid master curve coefficients. The surrogate forward modeling results showed that NNs are able to predict deflection-time histories from E(t) master curve coefficients and other layer properties very well. The NN inverse modeling results demonstrated the potential of NNs to backcalculate the E(t) master curve coefficients from single-drop FWD deflection-time history data, although the current prediction accuracies are not sufficient to recommend these models for practical implementation. Considering the complex nature of the problem investigated with many uncertainties involved, including the possible presence of dynamics during FWD testing (related to the presence and depth of stiff layer, inertial and wave propagation effects, etc.), the limitations of current FWD technology (integration errors, truncation issues, etc.), and the need for a rapid and simplified approach for routine implementation, future research recommendations have been provided making a strong case for an expanded research study.

Changes in Aortic Pulse Wave Velocity in Hypertension Post-Menopausal Women: Comparison Between Calcium Channel Blocker (CCB) Vs Angiotensin Receptor Blocker (ARB) Regimen

Objective: To compare effects of a non-renin-angiotensin system (RAS) blocker, using a CCB, or a RAS blocker, using an ARB regimen on the arterial stiffness reduction in postmenopausal hypertensive women. Methods: In this prospective study, a total of 125 hypertensive women (age: 61.4_6 yrs; 98% Caucasian; BW: 71.9_14 kg; BMI: 27.3_5 kg/m2; SBP/ DBP: 158_11/92_9 mmHg) were randomized between ARB (valsartan 320mg_HCTZ) and CCB (amlodipine 10mg _ HCTZ). The primary outcome was carotid-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Results: There were no significant differences in baseline demographic data between the two groups. Both treatments effectively lowered BP at the end of the study with similar (p>0.05) reductions in the valsartan (_22.9/_10.9 mmHg) and amlodipine based (_25.2/_11.7 mmHg) treatment groups. Despite a lower (p<0.05 for DBP) central SBP/DBP in the CCB group (_19.2/_10.3 mmHg) compared to the valsartan group (_15.7/_7.6 mmHg) at week 38, a similar reduction in carotid-femoral PWV (_1.7 vs _1.9 m/sec; p>0.05) was observed between both groups. The numerically larger BP reduction observed in the CCB group was associated with a much higher incidence of peripheral edema (77% vs 14%) than the valsartan group. Conclusion: In summary, BP lowering in postmenopausal women led to a reduction in arterial stiffness assessed by PWV measurement. Both regimens reduced PWV at 38 weeks of treatment to a similar degree, despite differences in BP lowering suggesting that the effect of RAS blockade to influence PWV may partly be independent of BP.

Diabetes care: opinions, needs and proposed solutions of Swiss patients and healthcare professionals: a qualitative study.

AIMS: To explore, both among patients with diabetes and healthcare professionals, opinions on current diabetes care and the development of the "Regional Diabetes Program". METHODS: We employed qualitative methods (focus groups - FG) and used purposive sampling strategy to recruit patients with diabetes and healthcare professionals. We conducted one diabetic and one professional FG in each of the four health regions of the canton of Vaud/Switzerland. The eight FGs were audio-taped and transcribed verbatim. Thematic analysis was then undertaken. RESULTS: Results showed variability in the perception of the quality of diabetes care, pointed to insufficient information regarding diabetes, and lack of collaboration. Participants also evoked patients' difficulties for self-management, as well as professionals' and patients' financial concerns. Proposed solutions included reinforcing existing structures, developing self-management education, and focusing on comprehensive and coordinated care, communication and teamwork. Patients and professionals were in favour of a "Regional Diabetes Program" tailored to the actors' needs, and viewed it as a means to reinforce existing care delivery. CONCLUSIONS: Patients and professionals pointed out similar problems and solutions but explored them differently. Combined with coming quantitative data, these results should help to further develop, adapt and implement the "Regional Diabetes Program".

A subcritical instability of wave-driven alongshore currents

The development of shear instabilities of a wave-driven alongshore current is investigated. In particular, we use weakly nonlinear theory to investigate the possibility that such instabilities, which have been observed at various sites on the U.S. coast and in the laboratory, can grow in linearly stable flows as a subcritical bifurcation by resonant triad interaction, as first suggested by Shrira eta/. [1997]. We examine a realistic longshore current profile and include the effects of eddy viscosity and bottom friction. We show that according to the weakly nonlinear theory, resonance is possible and that these linearly stable flows may exhibit explosive instabilities. We show that this phenomenon may occur also when there is only approximate resonance, which is more likely in nature. Furthermore, the size of the perturbation that is required to trigger the instability is shown in some circumstances to be consistent with the size of naturally occurring perturbations. Finally, we consider the differences between the present case examined and the more idealized case of Shrira et a/. [ 1997]. It is shown that there is a possibility of coupling between triads, due to the richer modal structure in more realistic flows, which may act to stabilize the flow and act against the development of subcritical bifurcations. Extensive numerical tests are called for.

On periodic solutions of 2-periodic Lyness difference equations

We study the existence of periodic solutions of the non--autonomous periodic Lyness' recurrence u_{n+2}=(a_n+u_{n+1})/u_n, where {a_n} is a cycle with positive values a,b and with positive initial conditions. It is known that for a=b=1 all the sequences generated by this recurrence are 5-periodic. We prove that for each pair (a,b) different from (1,1) there are infinitely many initial conditions giving rise to periodic sequences, and that the family of recurrences have almost all the even periods. If a is not equal to b, then any odd period, except 1, appears.