Les traitements de l'ostéoporose (à l'exception de la substitution hormonale et de ses dérivés) [Treatment of osteoporosis (with the exception of hormone replacement and its derivates]

Calcium and vitamin D supplementation are warranted for the treatment of osteoporosis, when other specific drugs are used. Vitamin D supplementation is necessary when the plasma level of 25-hydroxy-vitamin D is below 30 nmol/l (12 pg/l) in order to avoid any increase of the plasma parathyroid hormone level. Bisphosphonates are the most widely drugs used. Recent advances will provide patients with a more convenient therapeutically equivalent alternative: the once-weekly oral dosing regimen and probably the possibility to give infusions at intervals of up to one year. Parathyroid hormone administered subcutaneously daily produced a dramatic increase of trabecular and cortical bone mineral density, and an important decrease of vertebral and nonvertebral fracture risk. Strontium is a new original drug, which stimulates bone formation, and inhibits bone resorption. It significantly improves trabecular and cortical bone mass. Calcitonin not only prevents the recurrence of vertebral fractures, but possibly could decrease hip fractures risk. Hydrochlorothiazide preserves the bone mineral density, and decreases nonvertebral fracture risk, as showed in epidemiological studies. Large clinical trials with statins therapy in appropriate populations are required to find out whether these drugs have any role in preventing fractures.

Calcium reabsorption in the distal tubule: regulation by sodium, pH, and flow.

We developed a mathematical model of Ca transport along the late distal convoluted tubule (DCT2) and the connecting tubule (CNT) to investigate the mechanisms that regulate Ca reabsorption in the DCT2-CNT. The model accounts for apical Ca influx across transient receptor potential vanilloid 5 (TRPV5) channels and basolateral Ca efflux via plasma membrane Ca-ATPase pumps and type 1 Na/Ca exchangers (NCX1). Model simulations reproduce experimentally observed variations in Ca uptake as a function of extracellular pH, Na, and Mg concentration. Our results indicate that amiloride enhances Ca reabsorption in the DCT2-CNT predominantly by increasing the driving force across NCX1, thereby stimulating Ca efflux. They also suggest that because aldosterone upregulates both apical and basolateral Na transport pathways, it has a lesser impact on Ca reabsorption than amiloride. Conversely, the model predicts that full NCX1 inhibition and parathyroidectomy each augment the Ca load delivered to the collecting duct severalfold. In addition, our results suggest that regulation of TRPV5 activity by luminal pH has a small impact, per se, on transepithelial Ca fluxes; the reduction in Ca reabsorption induced by metabolic acidosis likely stems from decreases in TRPV5 expression. In contrast, elevations in luminal Ca are predicted to significantly decrease TRPV5 activity via the Ca-sensing receptor. Nevertheless, following the administration of furosemide, the calcium-sensing receptor-mediated increase in Ca reabsorption in the DCT2-CNT is calculated to be insufficient to prevent hypercalciuria. Altogether, our model predicts complex interactions between calcium and sodium reabsorption in the DCT2-CNT.

Evaluation of Electronic Speed Limit Signs on US 30, September, 2011

This study documents the speed reduction impacts of two dynamic, electronic school zone speed limit signs at United Community Schools between Ames and Boone, Iowa. The school facility is situated along US Highway 30, a rural four-lane divided expressway. Due to concerns about high speeds in the area, the Iowa Department of Transportation (DOT) decided to replace the original static school zone speed limit signs, which had flashing beacons during school start and dismissal times (Figure 1), with electronic speed signs that only display the reduced school speed limit of 55 mph during school arrival and dismissal times (Figure 2). The Center for Transportation Research and Education (CTRE) at Iowa State University (ISU) conducted a speed evaluation study one week before and 1 month, 7 months, and 14 or 15 months after the new signs were installed. Overall, the new dynamic school zone speed limit signs were more effective in reducing speeds than the original static signs with flashing beacons in the 1 month after period. During the 7 and 14 month after period, speeds increased slightly for the eastbound direction of traffic. However, the increases were consistent with overall speed increases that occurred independent of the signs. The dynamic, electronic signs were effective for the westbound direction of traffic for all time periods and for both start and dismissal times. Even though only modest changes in mean and 85th percentile speeds occurred, with the speed decreases, the number of vehicles exceeding the school speed limit decreased significantly, indicating the signs had a significant impact on high-end speeders.

Least limiting water range in soil under crop rotations and chiseling

Soil water availability to plants is affected by soil compaction and other variables. The Least Limiting Water Range (LLWR) comprises soil physical variables affecting root growth and soil water availability, and can be managed by either mechanical or biological methods. There is evidence that effects of crop rotations could last longer than chiseling, so the objective of this study was to assess the effect of soil chiseling or growing cover crops under no-till (NT) on the LLWR. Crop rotations involving triticale (X Triticosecale) and sunflower (Helianthus annuus) in the fall-winter associated with millet (Pennisetum glaucum), sorghum (Sorghum bicolor) and sunn hemp (Crotalaria juncea) as cover crops preceding soybean (Glycine max) were repeated for three consecutive years. In the treatment with chiseling (performed only in the first year), the area was left fallow between the fall-winter and summer crops. The experiment was carried out in Botucatu, São Paulo State, Brazil, from 2003 to 2006 on a Typic Rhodudalf. The LLWR was determined in soil samples taken from the layers 0-20 cm and 20- 40 cm, after chemical desiccation of the cover crops in December of the first and third year of the experiment. Chiseling decreases soil bulk density in the 0-20 cm soil layer, increasing the LLWR magnitude by lowering the soil water content at which penetration resistance reaches 2.0 MPa; this effect is present up to the third year after chiseling and can reach to a depth of 0.40 m. Crop rotations involving sunflower + sunn hemp, triticale + millet and triticale + sunn hemp for three years prevented soil bulk density from exceeding the critical soil bulk density in the 0- 0.20 m layer. This effect was observed to a depth of 0.40 m after three years of chiseling under crop rotations involving forage sorghum. Hence, chiseling and some crop rotations under no tillage are effective in increasing soil quality assessed by the LLWR.

Endoleak and in-stent thrombus detection with CT angiography in a thoracic aortic aneurysm phantom at different tube energies using filtered back projection and iterative algorithms.

PURPOSE: To determine the lower limit of dose reduction with hybrid and fully iterative reconstruction algorithms in detection of endoleaks and in-stent thrombus of thoracic aorta with computed tomographic (CT) angiography by applying protocols with different tube energies and automated tube current modulation. MATERIALS AND METHODS: The calcification insert of an anthropomorphic cardiac phantom was replaced with an aortic aneurysm model containing a stent, simulated endoleaks, and an intraluminal thrombus. CT was performed at tube energies of 120, 100, and 80 kVp with incrementally increasing noise indexes (NIs) of 16, 25, 34, 43, 52, 61, and 70 and a 2.5-mm section thickness. NI directly controls radiation exposure; a higher NI allows for greater image noise and decreases radiation. Images were reconstructed with filtered back projection (FBP) and hybrid and fully iterative algorithms. Five radiologists independently analyzed lesion conspicuity to assess sensitivity and specificity. Mean attenuation (in Hounsfield units) and standard deviation were measured in the aorta to calculate signal-to-noise ratio (SNR). Attenuation and SNR of different protocols and algorithms were analyzed with analysis of variance or Welch test depending on data distribution. RESULTS: Both sensitivity and specificity were 100% for simulated lesions on images with 2.5-mm section thickness and an NI of 25 (3.45 mGy), 34 (1.83 mGy), or 43 (1.16 mGy) at 120 kVp; an NI of 34 (1.98 mGy), 43 (1.23 mGy), or 61 (0.61 mGy) at 100 kVp; and an NI of 43 (1.46 mGy) or 70 (0.54 mGy) at 80 kVp. SNR values showed similar results. With the fully iterative algorithm, mean attenuation of the aorta decreased significantly in reduced-dose protocols in comparison with control protocols at 100 kVp (311 HU at 16 NI vs 290 HU at 70 NI, P ≤ .0011) and 80 kVp (400 HU at 16 NI vs 369 HU at 70 NI, P ≤ .0007). CONCLUSION: Endoleaks and in-stent thrombus of thoracic aorta were detectable to 1.46 mGy (80 kVp) with FBP, 1.23 mGy (100 kVp) with the hybrid algorithm, and 0.54 mGy (80 kVp) with the fully iterative algorithm.

Effect of compaction on microbial activity and carbon and nitrogen transformations in two oxisols with different mineralogy

The use of machinery in agricultural and forest management activities frequently increases soil compaction, resulting in greater soil density and microporosity, which in turn reduces hydraulic conductivity and O2 and CO2 diffusion rates, among other negative effects. Thus, soil compaction has the potential to affect soil microbial activity and the processes involved in organic matter decomposition and nutrient cycling. This study was carried out under controlled conditions to evaluate the effect of soil compaction on microbial activity and carbon (C) and nitrogen (N) mineralization. Two Oxisols with different mineralogy were utilized: a clayey oxidic-gibbsitic Typic Acrustox and a clayey kaolinitic Xantic Haplustox (Latossolo Vermelho-Amarelo ácrico - LVA, and Latossolo Amarelo distrófico - LA, respectively, in the Brazil Soil Classification System). Eight treatments (compaction levels) were assessed for each soil type in a complete block design, with six repetitions. The experimental unit consisted of PVC rings (height 6 cm, internal diameter 4.55 cm, volume 97.6 cm³). The PVC rings were filled with enough soil mass to reach a final density of 1.05 and 1.10 kg dm-3, respectively, in the LVA and LA. Then the soil samples were wetted (0.20 kg kg-1 = 80 % of field capacity) and compacted by a hydraulic press at pressures of 0, 60, 120, 240, 360, 540, 720 and 900 kPa. After soil compression the new bulk density was calculated according to the new volume occupied by the soil. Subsequently each PVC ring was placed within a 1 L plastic pot which was then tightly closed. The soils were incubated under aerobic conditions for 35 days and the basal respiration rate (CO2-C production) was estimated in the last two weeks. After the incubation period, the following soil chemical and microbiological properties were detremined: soil microbial biomass C (C MIC), total soil organic C (TOC), total N, and mineral N (NH4+-N and NO3--N). After that, mineral N, organic N and the rate of net N mineralization was calculated. Soil compaction increased NH4+-N and net N mineralization in both, LVA and LA, and NO3--N in the LVA; diminished the rate of TOC loss in both soils and the concentration of NO3--N in the LA and CO2-C in the LVA. It also decreased the C MIC at higher compaction levels in the LA. Thus, soil compaction decreases the TOC turnover probably due to increased physical protection of soil organic matter and lower aerobic microbial activity. Therefore, it is possible to conclude that under controlled conditions, the oxidic-gibbsitic Oxisol (LVA) was more susceptible to the effects of high compaction than the kaolinitic (LA) as far as organic matter cycling is concerned; and compaction pressures above 540 kPa reduced the total and organic nitrogen in the kaolinitic soil (LA), which was attributed to gaseous N losses.

Ferromagnetic instabilities in neutron matter at finite temperature with the Skyrme interaction

The properties of spin-polarized neutron matter are studied at both zero and finite temperature using Skyrme-type interactions. It is shown that the critical density at which ferromagnetism takes place decreases with temperature. This unexpected behavior is associated to an anomalous behavior of the entropy that becomes larger for the polarized phase than for the unpolarized one above a certain critical density. This fact is a consequence of the dependence of the entropy on the effective mass of the neutrons with different third spin component. A new constraint on the parameters of the effective Skyrme force is derived if this behavior is to be avoided.

How patch configuration affects the impact of disturbances on metapopulation persistence.

Disturbances affect metapopulations directly through reductions in population size and indirectly through habitat modification. We consider how metapopulation persistence is affected by different disturbance regimes and the way in which disturbances spread, when metapopulations are compact or elongated, using a stochastic spatially explicit model which includes metapopulation and habitat dynamics. We discover that the risk of population extinction is larger for spatially aggregated disturbances than for spatially random disturbances. By changing the spatial configuration of the patches in the system--leading to different proportions of edge and interior patches--we demonstrate that the probability of metapopulation extinction is smaller when the metapopulation is more compact. Both of these results become more pronounced when colonization connectivity decreases. Our results have important management implication as edge patches, which are invariably considered to be less important, may play an important role as disturbance refugia.

The epithelial sodium channel mediates the directionality of galvanotaxis in human keratinocytes.

Cellular directional migration in an electric field (galvanotaxis) is one of the mechanisms guiding cell movement in embryogenesis and in skin epidermal repair. The epithelial sodium channel (ENaC), in addition to its function of regulating sodium transport in kidney, has recently been found to modulate cell locomotory speed. Here we tested whether ENaC has an additional function of mediating the directional migration of galvanotaxis in keratinocytes. Genetic depletion of ENaC completely blocks only galvanotaxis and does not decrease migration speed. Overexpression of ENaC is sufficient to drive galvanotaxis in otherwise unresponsive cells. Pharmacologic blockade or maintenance of the open state of ENaC also decreases or increases, respectively, galvanotaxis, suggesting that the channel open state is responsible for the response. Stable lamellipodial extensions formed at the cathodal sides of wild-type cells at the start of galvanotaxis; these were absent in the ENaC knockout keratinocytes, suggesting that ENaC mediates galvanotaxis by generating stable lamellipodia that steer cell migration. We provide evidence that ENaC is required for directional migration of keratinocytes in an electric field, supporting a role for ENaC in skin wound healing.

Development of a Model for the Ice Scraping Process, October 1996

A laboratory study has been conducted with two aims in mind. The first goal was to develop a description of how a cutting edge scrapes ice from the road surface. The second goal was to investigate the extent, if any, to which serrated blades were better than un-serrated or "classical" blades at ice removal. The tests were conducted in the Ice Research Laboratory at the Iowa Institute of Hydraulic Research of the University of Iowa. A specialized testing machine, with a hydraulic ram capable of attaining scraping velocities of up to 30 m.p.h. was used in the testing. In order to determine the ice scraping process, the effects of scraping velocity, ice thickness, and blade geometry on the ice scraping forces were determined. Higher ice thickness lead to greater ice chipping (as opposed to pulverization at lower thicknesses) and thus lower loads. Behavior was observed at higher velocities. The study of blade geometry included the effect of rake angle, clearance angle, and flat width. The latter were found to be particularly important in developing a clear picture of the scraping process. As clearance angle decreases and flat width increases, the scraping loads show a marked increase, due to the need to re-compress pulverized ice fragments. The effect of serrations was to decrease the scraping forces. However, for the coarsest serrated blades (with the widest teeth and gaps) the quantity of ice removed was significantly less than for a classical blade. Finer serrations appear to be able to match the ice removal of classical blades at lower scraping loads. Thus, one of the recommendations of this study is to examine the use of serrated blades in the field. Preliminary work (by Nixon and Potter, 1996) suggests such work will be fruitful. A second and perhaps more challenging result of the study is that chipping of ice is more preferable to pulverization of the ice. How such chipping can be forced to occur is at present an open question.

Effects of age, birth cohort and period of death on Swiss cancer mortality, 1951-1984.

Swiss death certification data over the period 1951-1984 for total cancer mortality and 30 major cancer sites in the population aged 25 to 74 years were analysed using a log-linear Poisson model with arbitrary constraints on the parameters to isolate the effects of birth cohort, calendar period of death and age. The overall pattern of total cancer mortality in males was stable for period values and showed some moderate decreases in cohort values restricted to the generations born after 1930. Cancer mortality trends were more favourable in females, with steady, though moderate, declines in both cohort and period values. According to the estimates from the model, the worst affected generation for male lung cancer was that born around 1910, and a flattening of trends or some moderate decline was observed for more recent cohorts, although this decline was considerably more limited than in other European countries. There were decreases in cohort and period values for stomach, intestine and oesophageal cancer in both sexes and (cervix) uteri in females. Increases were observed in both cohort and period trends for pancreas and liver in males and for several other neoplasms, including prostate, brain, leukaemias and lymphomas, restricted, however, for the latter sites, to the earlier cohorts and hence partly attributable to improved diagnosis and certification in the elderly. Although age values for lung cancer in females were around 10-times lower than in males, upward trends in female lung cancer cohort values were observed in subsequent cohorts and for period values from the late 1960's onwards. Therefore, future trends in female lung cancer mortality should continue to be monitored. The application of these age/period/cohort models thus provides a summary guide for the reading and interpretation of cancer mortality trends, although it cannot replace careful inspection of single age-specific rates.

Microscopic description of the twist mode in normal and superfluid trapped Fermi gases

We investigate the "twist" mode (rotation of the upper against the lower hemisphere) of a dilute atomic Fermi gas in a spherical trap. The normal and superfluid phases are considered. The linear response to this external perturbation is calculated within the microscopic Hartree-Fock-Bogoliubov approach. In the normal phase the excitation spectrum is concentrated in a rather narrow peak very close to the trapping frequency. In the superfluid phase the strength starts to be damped and fragmented and the collectivity of the mode is progressively lost when the temperature decreases. In the weak-pairing regime some reminiscence of the collective motion still exists, whereas in the strong-pairing regime the twist mode is completely washed out. The disappearance of the twist mode in the strong-pairing regime with decreasing temperature is interpreted in the framework of the two-fluid model.

External fluctuations in a pattern-forming instability

The effect of external fluctuations on the formation of spatial patterns is analyzed by means of a stochastic Swift-Hohenberg model with multiplicative space-correlated noise. Numerical simulations in two dimensions show a shift of the bifurcation point controlled by the intensity of the multiplicative noise. This shift takes place in the ordering direction (i.e., produces patterns), but its magnitude decreases with that of the noise correlation length. Analytical arguments are presented to explain these facts.

Dynamical properties of nonmarkovian stochastic differential equations

We study nonstationary non-Markovian processes defined by Langevin-type stochastic differential equations with an OrnsteinUhlenbeck driving force. We concentrate on the long time limit of the dynamical evolution. We derive an approximate equation for the correlation function of a nonlinear nonstationary non-Markovian process, and we discuss its consequences. Non-Markovicity can introduce a dependence on noise parameters in the dynamics of the correlation function in cases in which it becomes independent of these parameters in the Markovian limit. Several examples are discussed in which the relaxation time increases with respect to the Markovian limit. For a Brownian harmonic oscillator with fluctuating frequency, the non-Markovicity of the process decreases the domain of stability of the system, and it can change an infradamped evolution into an overdamped one.

Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro.

Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited because of its cardiotoxicity. Cell death is a key component in DOX-induced cardiotoxicity, but its mechanisms are elusive. Here, we explore the role of superoxide, nitric oxide (NO), and peroxynitrite in DOX-induced cell death using both in vivo and in vitro models of cardiotoxicity. Western blot analysis, real-time PCR, immunohistochemistry, flow cytometry, fluorescent microscopy, and biochemical assays were used to determine the markers of apoptosis/necrosis and sources of NO and superoxide and their production. Left ventricular function was measured by a pressure-volume system. We demonstrated increases in myocardial apoptosis (caspase-3 cleavage/activity, cytochrome c release, and TUNEL), inducible NO synthase (iNOS) expression, mitochondrial superoxide generation, 3-nitrotyrosine (NT) formation, matrix metalloproteinase (MMP)-2/MMP-9 gene expression, poly(ADP-ribose) polymerase activation [without major changes in NAD(P)H oxidase isoform 1, NAD(P)H oxidase isoform 2, p22(phox), p40(phox), p47(phox), p67(phox), xanthine oxidase, endothelial NOS, and neuronal NOS expression] and decreases in myocardial contractility, catalase, and glutathione peroxidase activities 5 days after DOX treatment to mice. All these effects of DOX were markedly attenuated by peroxynitrite scavengers. Doxorubicin dose dependently increased mitochondrial superoxide and NT generation and apoptosis/necrosis in cardiac-derived H9c2 cells. DOX- or peroxynitrite-induced apoptosis/necrosis positively correlated with intracellular NT formation and could be abolished by peroxynitrite scavengers. DOX-induced cell death and NT formation were also attenuated by selective iNOS inhibitors or in iNOS knockout mice. Various NO donors when coadministered with DOX but not alone dramatically enhanced DOX-induced cell death with concomitant increased NT formation. DOX-induced cell death was also attenuated by cell-permeable SOD but not by cell-permeable catalase, the xanthine oxidase inhibitor allopurinol, or the NADPH oxidase inhibitors apocynine or diphenylene iodonium. Thus, peroxynitrite is a major trigger of DOX-induced cell death both in vivo and in vivo, and the modulation of the pathways leading to its generation or its effective neutralization can be of significant therapeutic benefit.