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Pharmacokinetic/pharmacodynamic (PK/PD) modelling is a discipline currently under the umbrella of pharmacometrics, and aims to describe, understand and predict the time course of in vivo drug action.
In general PK/PD comprises three major elements: (1) pharmacokinetics (PK), (2) pharmacodynamics (PD), and (3) disease progression. However, given the fact that anaesthesia procedures take place in short periods of time, where the general state of the patient remains unaltered, in this chapter we will limit the focus to the interrelationship between PK and PD.
This study assessed the in vitro anthelmintic (AH) activity of methanol and acetone:water leaf extracts from Annona squamosa, A. muricata and A. reticulata against Haemonchus contortus eggs. The egg hatch test was used to determine the effective concentrations required to inhibit 50% of eggs hatching (EC50). The role of polyphenols on AH activity was measured through bioassays with and without polyvinylpolypyrrolidone (PVPP). Methanolic extracts mainly caused the death of eggs at the morula stage (ovicidal activity). Meanwhile, acetone:water extracts caused egg-hatching failure of developed larvae (larvae failing eclosion (LFE) activity). The lowest EC50 values against H. contortus eggs were observed for the methanolic extracts from A. reticulata and A. muricata (274.2 and 382.9 µg/ml, respectively). From the six extracts evaluated, the methanolic extracts of A. muricata, A. reticulata and A. squamosa showed the highest ovicidal activity, resulting in 98.9%, 92.8% and 95.1% egg mortality, respectively. When the methanolic extract of A. squamosa was incubated with PVPP, its AH activity increased. Similarly, when acetone:water extracts of A. muriata and A. reticulata were incubated with PVPP, their LFE activity increased. Alkaloids were only evident in methanolic extracts, irrespective of PVPP incubation. The presence of acetogenins was not observed. In conclusion, methanolic extracts obtained from leaves of A. muricata, A. reticulata and A. squamosa showed ovicidal activity affecting the morula of H. contortus eggs, with minor LFE activity. Meanwhile, acetone:water extracts showed mostly LFE activity, with a lower proportion of ovicidal activity.
Pyrethroid insecticides were intensively used against Cydia pomonella in the Río Negro and Neuquén valley, main production area of pome fruits in Argentina. Therefore, the first objective was to evaluate lambda-cyhalothrin resistance levels in C. pomonella larvae from orchards in this area that are currently under pyrethroids treatments. The second objective was to evaluate the frequency of kdr mutation in C. pomonella across Argentina. High levels of resistance to lambda-cyhalothrin (resistance ratios > 30) were determined in all the populations evaluated. The L1014F (kdr) mutation was evaluated in 355 diapausing larvae collected in 12 orchards from San Juan to Santa Cruz provinces (1690 km away from each other). The highest frequency of kdr mutation was determined in larvae from the Río Negro and Neuquén valley (0.61), followed by those from Mendoza (0.36). The kdr allele was absent or present at very low frequencies in orchards subjected to low pyrethroid pressure. The frequency of detection of kdr mutation in C. pomonella from Argentina is related to the use of pyrethroids against this pest in different areas. Target-site insensitivity is, at least, one of the mechanisms involved in resistance to lambda-cyhalothrin in codling moth from the Río Negro and Neuquén valley.
A numerical study of the saturation process inside a rectangular open cavity is presented. Previous experiments and linear stability analysis of the problem completely described the flow in its onset, as well as in a saturated regime, characterized by three-dimensional centrifugal modes. The morphology of the modes found in the experiments matched the ones predicted by linear analysis, but with a shift in frequencies for the oscillating modes. A three-dimensional incompressible direct numerical simulation (DNS) is employed for a detailed investigation of the saturation process inside a cavity with dimensions similar to the one used in the experiments, to further explain the behaviour of these modes. In this work, periodic boundary conditions are first imposed to better understand the effect of the saturation process far from the walls. Then, the effects of spanwise solid wall boundary conditions are investigated with a DNS reproducing the full dynamics of the experiments. The main flow structures are identified using the dynamic mode decomposition technique and compared with previous experimental and linear stability analysis results. The main reason for the aforementioned shift in frequency is explained in this paper, as it is a function of the velocity of the main recirculating vortex.
New Super-High-Density (SHD) olive orchards designed for mechanical harvesting are increasing very rapidly in Spain. Most studies have focused in effectively removing the olive fruit, however the machine needs to put significant amount of energy on the canopy that could result in structural damage or extra stress on the trees. During harvest, a series of 3-axis accelerometers were installed on the tree structure in order to register vibration patterns. A LiDAR (Light Detection and Ranging) and a camera sensing device were also mounted on a tractor. Before and after harvest measurements showed significant differences in the LiDAR and image data. A fast estimate of the damage produced by an over-the-row harvester with contactless sensing could be useful information for adjusting the machine parameters in each olive grove automatically in the future.
Molluscs are subjected to intense harvesting in many areas around the world. Conservation measures have been developed to preserve populations of an overexploited gastropod species, the abalone Haliotis tuberculata coccinea. This species was surveyed in subtidal localities throughout coastal Tenerife, Canary Islands over the last two decades (1994–2014). A clear indicator of non-recovery was observed in the decrease of mean size throughout the last two decades, even after the inclusion of this species in the Regional Catalogue of Endangered Species. The mean size of abalones decreased from 33.5 mm (1994) to 28–29 mm (2002 and 2014), corresponding to sub-adult individuals. The structure of size classes was typical of an overexploited species, with reduced occurrence of large individuals (>50 mm). Several factors might explain this pattern such as illegal harvesting, proliferation of featureless benthos and a decrease of suitable habitats for colonization and settlement. Complementary conservation actions are urgently needed to preserve this species in the area studied.
We present results from an ongoing survey of the ionized gas kinematics in Virgo cluster spiral galaxies using Fabry-Perot (FP) interferometry. Our goal is to study the environmental effects on galaxy evolution in the Virgo cluster. We report here on the Hα distribution map and velocity field of NGC 4438, an interacting galaxy near the centre of the cluster.
V647 Tau was observed during a 1997 STEPHI campaign; 228 hr of observations in v were obtained, together with another 50 hr of simultaneous data in y. The data were analyzed and main results are discussed in the text.
We acquired multisite observations of the newly discovered rapidly oscillating Ap star HD 122970. A frequency analysis shows the presence of two independent modes, one singlet and one equally spaced triplet. By applying the oblique pulsator model and asymptotic theory we infer that the triplet originates from a distorted dipole mode and that the singlet most probably corresponds to a radial mode.
For δ Sct stars, the theoretical predictions of a non-adiabatic pulsation code are very dependent on the characteristics of the thin convective envelope of the models (Balona & Evers 1999). The treatment of the non-adiabatic interaction between convection and pulsation also has a significant impact on the results, particularly near the red edge of the instability strip. The non-adiabatic theoretical predictions can be tested upon observations by comparing them to the amplitude ratios and phase differences as observed in different color passbands (Dupret et al. 2003). In the first part of this paper, we compare the results obtained by adopting different treatments of convection in the interior and atmosphere models: mixing-length theory (MLT) and full spectrum of turbulence (FST) (Canuto et al. 1996, CGM). In the second part, we examine the problem of the interaction between convection and pulsation and compare the mode stability obtained with and without including time-dependent convection in our non-adiabatic code.
We have recently identified a young, very red (J − Ks = 2.47 mag) late L-type companion at 8.06” ± 0.03” (~102 AU) from a previously unrecognized M dwarf. We determined the parallactic distance of the system to be 12.7±1.0 pc. Non-detection of lithium and the kinematics of the primary allowed us to constrain the age of the system in the range of 150–300 Myr. By comparison with theoretical evolutionary models we derived a mass of 73+20−15MJup for the primary, at around the substellar mass regime and 11.2+9.7−1.8MJup for the secondary, near the deuterium burning mass limit.
In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile. The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.
Harvesting solar energy, is only one of the incentives of incorporating photosynthetic proteins in electrochemical devices. Understanding the interface of photosynthetic protein complexes and organic\inorganic underlying electrodes can give rise to development of new generation of nano-bioelectronics for other applications such as sensing, as well. Previous approaches in fabricating photosynthetic bio-hybrid electrochemical solar cells were mainly based on metallic electrodes with protein complexes attached, either directly or through linker molecules. Due to the energy band structure in semiconductors, they potentially can be useful for selective charge transfer in an electrochemical device. In the current study, a two terminal sealed bio-hybrid solar cell device was fabricated comprising of hydrothermally grown ZnO nanowires on fluorine doped tin oxide (FTO) glass working electrode, a Pt counter electrode, and methyl viologen (MV) as a single diffusible redox mediator. The ZnO working electrode was initially characterized using scanning electron microscopy (XRD) and X-ray diffraction (XRD). A solution of dimeric Rhodobacter sphaeroides – light harvesting 1 (RC-LH1) core complexes and redox electrolyte was injected into the cavity between working and counter electrodes. Such structure resulted in ∼0.64 µA.cm-2 photocurrent density and ∼0.24 V open circuit potential difference in the dark and under illumination. Additionally, the device stability tests demonstrated that the current response of such devices remained unchanged after 33 hours storage in the dark.
Since the sixteenth century, Western literature has produced picaresque novels penned by authors across Europe, from Alemán, Cervantes, Lesage and Defoe to Cela and Mann. Contemporary authors of neopicaresque are renewing this traditional form to express twenty-first-century concerns. Notwithstanding its major contribution to literary history, as one of the founding forms of the modern novel, the picaresque remains a controversial literary category, and its definition is still much contested. The Picaresque Novel in Western Literature examines the development of the picaresque, chronologically and geographically, from its origins in sixteenth-century Spain to the neopicaresque in Europe and the United States.