Why are physicians not prescribing diuretics more frequently in the management of hypertension?

Diuretics have again been recommended by the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) as one of the first-choice medications in the management of hypertension. This recommendation is based on the results of numerous randomized, diuretic-based, long-term controlled clinical trials that have demonstrated a reduction in both cerebrovascular and cardiovascular morbidity. Despite this and other national recommendations, the use of diuretics has steadily decreased over the past 15 years. Reasons include heavy promotion of other medications and the perception that diuretics produce adverse metabolic effects and do not reduce coronary heart disease events. Data, however, indicate that (1) changes in glucose and cholesterol metabolism are minor, especially with the smaller doses now being used; (2) cardiovascular morbidity and mortality have been reduced in hypertensive patients, even in those with hyperlipidemia or diabetes, when diuretics are used; and (3) concerns about hypokalemia-induced arrhythmias have been overstated. While special indications exist for other medications in the treatment of hypertension, for example, use of an angiotensin-converting enzyme inhibitor (usually in addition to a diuretic) for a patient with heart failure or diabetic nephropathy, most patients, including those with hyperlipidemia or glucose intolerance, can be effectively treated with a diuretic as initial therapy or as part of a combination regimen. Diuretics should be used more not less frequently; use of diuretics would reduce the number of resistant hypertensive patients.     

Polyplexes of polyethylenimine and per-N-methylated polyethylenimine-cytotoxicity and transfection efficiency

For non-viral gene delivery, the carriers for DNA transfer into cells must be vastly improved. The branched cationic polymer polyethylenimine has been described as an efficient gene carrier. However, polyethylenimine was demonstrated to mediate substantial cytotoxicity. Therefore, this study is aimed at investigating per-N-methylated polyethylenimine, which is thought to have a much lower cytotoxicity due to its lower charge density. Results from a gel retardation assay and laser light scattering indicated that per-N-methylated polyethylenimine condenses DNA into small and compact nanoparticles with a mean diameter <150 nm. Furthermore, polyplexes of polyethylenimine and per-N-methylated polyethylenimine with DNA had a positive zeta potential and the polymers protected DNA from nuclease-mediated digestion. The transfection efficiency of polyethylenimine and per-N-methylated polyethylenimine was tested in CHO-K1 cells. Using green fluorescent protein as reporter gene and flow cytometry analysis, we demonstrated that per-N-methylated polyethylenimine has a lower cytotoxicity, but also a significantly lower transfection efficiency. Using propidium iodide staining, we could additionally distinguish between viable and dead cells. At NP > or = 12, per-N-methylated polyethylenimine showed a much higher cell viability and the ratio of viable and transfected cells to dead and transfected cells was about 1.5 to 1.7 fold higher than for polyethylenimine. The results of cell viability from flow cytometry analysis were confirmed by the MTS assay. Using luciferase reporter gene for transfection experiments, the gene expression of per-N-methylated polyethylenimine was lower at NP 6, 12 and 18 as compared to polyethylenimine, but at NP 24 it yielded similar levels.     

Performance in a complex task and breathing under odor exposure

We investigated the influences of odor exposure on performance and on breathing measures. The task was composed of tracking, short-term memory, and peripheral reaction parts. During rest or while performing the task, 12 participants were exposed to 4 different odors in 2 intensities. The higher intensity of the malodors induced a short-term decrement in mean inspiration flow (Vi/Ti) after stimulus onset and impaired performance in the short-term memory task, as compared with control trials; no effect was found for the positively judged odors. The study suggests that a distractor as simple as a bad smell may pull a person off task, however briefly, and may result in a detriment to performance. Actual or potential applications of this research involve designing or securing tasks in such a way that a brief withdrawal of attention does not have fatal consequences.     

Biogeochemical processes and microbial characteristics across groundwater-surface water boundaries of the Hanford Reach of the Columbia River

Biogeochemical processes within riverbed hyporheic zones (HZ) can potentially impact the fate and transport of contaminants. We evaluated a modified freeze core technique for the collection of intact cobble-bed samples from the Columbia River HZ along a stretch of the Hanford Reach in Washington State and investigated microbiological and geochemical parameters of corresponding frozen and unfrozen samples. During three sampling periods (March, May, and November 2000), relatively high numbers of viable aerobic heterotrophic bacteria were recovered from both unfrozen (10(6)-10(7) cfu/g) and frozen samples (10(5)-10(6) cfu/g). Relatively large populations of sulfate-, nitrate-, and iron-reducing bacteria were present, and significant concentrations of acid-volatile sulfide were measured in some samples, indicating that anoxic regions exist within this zone. Cr(VI), a priority groundwater pollutant on adjacent U.S. Department of Energy lands, was probably removed from solution in HZ samples by a combination of microbial activity and chemical reduction, presumably via products of anaerobic microbial metabolism. These results suggest that biogeochemical processes in the Columbia River HZ may contribute to the natural attenuation of Cr(VI). Although freezing modestly diminished recovery of viable bacteria, freeze core techniques proved reliable for the collection of intact hyporheic sediments.     

Complexes between monoclonal antibodies and receptor fragments with a common cold virus: determination of stoichiometry by capillary electrophoresis

Complex formation between monoclonal antibodies or soluble receptor fragments and a human rhinovirus is quantified by relating the concentration of the antibody or receptor under equilibrium conditions to the initial concentration of the virus. Within a given concentration range of the reactants, the shape of the resulting curve depends only on the value of the dissociation constant of the particular system studied. Using antibodies and receptor fragments, cases for high, low, and intermediate affinity were investigated. For high-affinity systems, the curve approximates a decaying straight line and the binding stoichiometry can be accurately determined from the intercept with the x-axis. For the case of intermediate affinity, the curve can be linearized at low virus concentrations with the receptors present in large excess. Extrapolation of this line allows derivation of the binding stoichiometry from the intercept with the x-axis, although with less accuracy. For intermediate affinities, an estimate of the dissociation constant can be obtained from fitting the curve to the data points measured. Finally, in the case of low affinity none of the binding parameters can be quantified, although a rough estimate of the lower limit of the dissociation constant is possible. The method was applied for two different monoclonal antibodies, a Fab fragment and a receptor fragment, binding to human rhinovirus serotype 2. Thirty copies of the monoclonal antibody 8F5 were found to bind to the virion, which is in agreement with data from electron cryomicroscopy. The complex between monovalent human very-low-density lipoprotein receptor encompassing repeats 2 and 3 and human rhinovirus serotype 2 showed 60 receptor molecules bound per virion.     

Optimization of relative tool position in accumulative double sided incremental forming using finite element analysis and model bias correction

Double-Sided Incremental Forming (DSIF) uses two small, independently moving, hemispherical tools on either side of the sheet to form a desired shape by following a predefined tool path. This study was motivated by the observation that the relative tool position of the tools, specified in the tool path generation algorithm, affects the formed geometric accuracy. A methodology for defining the relative tool positioning in the tool path generation algorithm based on local part geometry is proposed using simplified Finite Element Analysis (FEA) and sample physical experiments combined with Gaussian Process modeling techniques. This approach can take into account the mechanics of deformation in DSIF explicitly and physical compliance of the DSIF machine implicitly. Physical experiments were performed to demonstrate the effectiveness of the proposed framework.     

A stereophonic acoustic signal extraction scheme for noisy and reverberant environments

In this contribution, a novel two-channel acoustic front-end for robust automatic speech recognition in adverse acoustic environments with nonstationary interference and reverberation is proposed. From a MISO system perspective, a statistically optimum source signal extraction scheme based on the multichannel Wiener filter (MWF) is discussed for application in noisy and underdetermined scenarios. For free-field and diffuse noise conditions, this optimum scheme reduces to a Delay & Sum beamformer followed by a single-channel Wiener postfilter. Scenarios with multiple simultaneously interfering sources and background noise are usually modeled by a diffuse noise field. However, in reality, the free-field assumption is very weak because of the reverberant nature of acoustic environments. Therefore, we propose to estimate this simplified MWF solution in each frequency bin separately to cope with reverberation. We show that this approach can very efficiently be realized by the combination of a blocking matrix based on semi-blind source separation (‘directional BSS’), which provides a continuously updated reference of all undesired noise and interference components separated from the desired source and its reflections, and a single-channel Wiener postfilter. Moreover, it is shown, how the obtained reference signal of all undesired components can efficiently be used to realize the Wiener postfilter, and at the same time, generalizes well-known postfilter realizations. The proposed front-end and its integration into an automatic speech recognition (ASR) system are analyzed and evaluated in noisy living-room-like environments according to the PASCAL CHiME challenge. A comparison to a simplified front-end based on a free-field assumption shows that the introduced system substantially improves the speech quality and the recognition performance under the considered adverse conditions.     

3D deep X-ray lithography for producing a multi-channel Fourier transform interferometer

We introduce a modified LIGA process architecture to manufacture a static lamellar grating Fourier-transform spectrometer invented by Moser and Möller (European patent EP 0 765 488 B1, 1994). Such spectrometers hold unique advantages over common Michelson-type FTIRs including high time resolution, speed, compactness, and robustness. To cope with the spectrometer’s demand for precise high-aspect-ratio micro-fabrication, we present a modified LIGA process which enhances the X-ray lithography by means of a moving mask technique (Heussler and Moser Lithography method and apparatus PCT/SG2011/000376, 2011). The technique relies on independently moving multiple masks stacked on top of each other during the lithographic step and thus allows to locally vary the deposited dose in a positive tone photoresist. First manufacturing results as well as a performance test of a prototype spectrometer are reported.