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Mice homozygous for the beta-amyloid precursor protein (APP) were viable and fertile, but mutant mice weighed 15%-20% less than wild-type controls. Neurological evaluation of homozygous mice revealed decreased locomotor activity and forelimb grip strength, indicating impaired neuronal and muscular function. They also exhibited gliosis at 14 weeks of age, enforcing previous result that misprocessed APP leads to impaired neuronal function.

• We used 11 sites' lab-confirmed influenza data to elucidate meteorological effects. • Primarily, cold temperature favored influenza A and B in temperate and subtropics. • Temperature-to-influenza A exhibited U-shape association in subtropics and tropics. • Absolute humidity was negatively associated with influenza B activity in temperate. • However, it was positively associated with both influenza in subtropics and tropics. To elucidate the effects of meteorological variations on the activity of influenza A and B in 11 sites across different climate regions. Daily numbers of laboratory-confirmed influenza A and B cases from 2011–2015 were collected from study sites where the corresponding daily mean temperature, relative humidity, wind speed and daily precipitation amount were used for boosted regression trees analysis on the marginal associations and the interaction effects. Cold temperature was a major determinant that favored both influenza A and B in temperate and subtropical sites. Temperature-to-influenza A, but not influenza B, exhibited a U-shape association in subtropical and tropical sites. High relative humidity was also associated with influenza activities but was less consistent with influenza B activity. Compared with relative humidity, absolute humidity had a stronger association - it was negatively associated with influenza B activity in temperate zones, but was positively associated with both influenza A and B in subtropical and tropical zones. The association between meteorological factors and with influenza activity is virus type specific and climate dependent. The heavy influence of temperature on influenza activity across climate zones implies that global warming is likely to have an impact on the influenza burden. [ABSTRACT FROM AUTHOR]

Coronary artery ectasia (CAE), or aneurysm (ballooning of blood vessel), occurs in one to five percent of adults, and is usually due to atherosclerosis and possibly inflammation. In particular, partial blockage of the right coronary artery by fatty deposits known as plaques can lead to compensatory ballooning of the artery. Most of the adults with CAE have been reported to have heart attacks or long-term angina. A case is reported of a 65-year-old man with a long history of high blood pressure who developed suffocating chest pain. A heart attack, which is due to coronary ischemia (loss of blood flow to heart muscle), was diagnosed, and cardiac catheterization showed CAE with thrombus (clot) in the right coronary artery. The patient was treated with streptokinase (which can break up clots), and then with heparin and aspirin, which are anti-clotting agents. The thrombus dissolved within seven days, and heart function was good. One year later, the patient had no further symptoms. The report indicates that thrombolytic (clot-destroying) therapy can be effective in preserving heart function and can resolve thrombosis involved in coronary artery ectasia. (Consumer Summary produced by Reliance Medical Information, Inc.)

Synovial fluid flow in articular joint capsule plays an important role during mixed mode lubrication. However, the actual fluid flow behaviour during cartilage contact has not been fully understood so far. This is due to the difficulties in measuring the gap permeability using conventional experimental techniques. The problem becomes further complicated with consideration of the cartilage surface roughness. Here a validated numerical study was developed to quantify the gap permeability of lateral synovial fluid flow. Both macro- and micro-scale gap flow models were created based on Darcy's law at the macro-scale and the Navier-stokes equation at the micro-scale. To generate model inputs, the cartilage topography was numerically synthesised based on the experimental measurements of bovine medial tibia cartilage surface roughness using Dektak Stylus Profilers. The experimental results show that the average roughness height R a is 1.97 μm and root-mean-square roughness height R q is 2.44 μm, while the correlation lengths of the secondary and tertiary undulations are round 100 μm and 20 μm, respectively. The numerical results indicate that the contact gap height and fluid pressure gradient are two critical parameters which significantly affect the gap permeability. As the contact gap closes, there is a decrease in gap permeability, and most importantly, the gap permeability is also very sensitive to the fluid pressure gradient. Furthermore, with gap closure, the permeability of the contact gap gradually approaches that of the cartilage tissue, at which point the contact gap is functional closed. This occurs at a contact gap height around 1 μm and fluid pressure gradient below 5 × 105 Pa/m in this study. • Study fluid flow in cartilage gap by developing validated numerical models. • Synthesise cartilage topography using the measurements from Dektak Stylus Profilers. • Contact gap height and fluid pressure gradient greatly affect the gap permeability. • The gap is functionally closed at particular gap height and pressure gradient. [ABSTRACT FROM AUTHOR]

This study used ProMax ® 4.0 process simulator (rate–based model) to conduct a parametric sensitivity of carbon dioxide (CO 2 ) capture from a 115 MW coal–fired power plant (Boundary Dam 3 power plant) using monoethanolamine (MEA) and diethanolamine (DEA) blend. Saskatchewan Power Corporation (SaskPower), Canada provided the flue gas composition used in this study. The validated simulation was used to determine the effects of some process variables (independent process variables) on different dependent process variables. The independent process variables are flue gas temperature (T FG , o C), lean amine temperature (T LA , o C), lean amine flow rate (F LA , tonne/day), lean amine concentration difference (C MEA–DEA , kmol/m 3 ) and reboiler temperature (T REB , o C). The dependent process variables are MEA and DEA vaporization from the absorber, CO 2 absorption efficiency (%), regeneration energy (GJ/tonne CO 2 ), rich amine loading (RAL, mol CO 2 /mol amine) and lean amine loading (LAL, mol CO 2 /mol amine). Amine degradation was investigated by the O 2 absorption rate (tonne O 2 /day), NO absorption rate (tonne NO/day) and NO 2 absorption rate (tonne NO 2 /day). The vaporization rates of MEA (tonne MEA/day) and DEA (tonne DEA/day) were also investigated. The contribution of amine and water make–up costs, regeneration energy, pump electrical energy, blower electrical energy and compressor electrical energy towards variable operating expenditure (V–OPEX) were also investigated. Results showed that NO also contributes to amine degradation. From the parametric analysis it was observed that T REB has the greatest influence on most of the dependent process variables. It was also discovered that the regeneration energy, compressor electrical energy and amine, water make–up cost and cooling water contributed 82.5%, 12.3%, 1.1%, 0.9% and 0.5% of the V–OPEX respectively. [ABSTRACT FROM AUTHOR]

Recently we presented a computational model of articular cartilage calibrated for normal human tissue explants. This model was able to capture the transient deformation of cartilage experiencing a cyclic load. The model takes into account the tension-compression nonlinearity of the cartilage and incorporates the dependency of the compressive stiffness and fluid permeability of cartilage on the deformation-dependent aggrecan concentration in cartilage tissue. As such it represents a leading constitutive model of articular cartilage. Here we build on the previous study to develop an experimentally validated computational model to simulate mechanical consolidation response of intact and previously injured cartilage under sustained static loading, to develop our understanding of the implications for rates of tissue damage. We see that the type of prior injuries compromise the cartilage function in different ways. Relatively rapid consolidation is predicted for cartilage with a complete meniscectomy and that with a full thickness defect, indicating the inability of cartilage with such injuries to sustain interstitial fluid pressurisation for long periods of time, as does uninjured cartilage. By comparing the consolidation response of articular cartilage predicted by computational model against experimental measurements of the apparent friction coefficient following static loading, we find a strong linear positive correlation exists between cartilage degree of consolidation (DoC) and friction coefficient at the joint. As the DoC of articular cartilages can be estimated in vivo via medical imaging, the DoC can be used as an index to non-invasively evaluate the apparent friction coefficient between opposing cartilage surfaces, and so estimate the likelihood of frictional surface wear and/or cartilage damage. [ABSTRACT FROM AUTHOR]

Although dogs are widely trained and deployed for odor detection work, relatively little research has investigated procedures that may more efficiently train or increase detection performance. Prior research in rodents and humans suggests that odorant exposure may enhance sensitivity to that odorant; however, other research has suggested that exposure may have the opposite effect. Our aim was to assess whether exposure to odorants influences dogs’ sensitivity to those odorants on a subsequent operant task. We specifically tested whether simply being non-contingently exposed to an odorant or being exposed to an odorant in an appetitive Pavlovian conditioning paradigm influenced dogs’ sensitivity to that odorant. In a pre- post-test design we assessed changes in dogs’ sensitivity to two odorants. In the first phase, dogs’ sensitivity to both odorants was assessed using a descending series of half (binary) dilutions presented using a liquid-dilution olfactometer. Then half the dogs were non-contingently exposed or Pavlovian conditioned to one odorant while the second odorant remained an unexposed control. Sensitivity to both odorants was then re-assessed using the same procedures as during baseline. Dogs showed a significant increase in sensitivity to the Pavlovian conditioned odorant compared to both the control odorant ( p < 0.01) and compared to the non-contingently exposed odorant ( p < 0.01). These results suggest that Pavlovian conditioning may be a simple procedure to enhance olfactory sensitivity to a target odorant. [ABSTRACT FROM AUTHOR]

• Carbon dioxide (CO 2) levels are important in managing neurologic conditions. • Spreading depolarizations (SD) are a pathologic mechanism of cerebral cortex. • CO 2 levels did not impact SD characteristics in normoxic or hypoxic rat brain. • Mean arterial pressure negatively correlated with SD duration. • The role of CO 2 warrants investigation in conditions of acute focal brain injury. Patients with traumatic brain injury are typically maintained at low-normal levels of arterial partial pressure of carbon dioxide (P a CO 2) to counteract the risk of elevated intracranial pressure during intensive care. However, several studies suggest that management at hypercarbic levels may have therapeutic benefit. Here we examined the impact of CO 2 levels on spreading depolarizations (SD), a mechanism and marker of acute lesion development in stroke and brain trauma. In an acute preparation of mechanically ventilated (30/70 O 2 /N 2) female rats, SDs were evoked by cortical KCl application and monitored by electrophysiology and laser doppler flowmetry; CO 2 levels were adjusted by ventilator settings and supplemental CO 2. During 90 min of KCl application, rats were maintained at hypocapnia (end-tidal CO 2 22 ± 2 mmHg) or hypercapnia (57 ± 4 mmHg) but did not differ significantly in arterial pH (7.31 ± 0.10 vs. 7.22 ± 0.08, p = 0.31) or other variables. Surprisingly, there was no difference between groups in the number of SDs recorded (10.7 ± 4.2 vs. 11.7 ± 3.1; n = 3 rats/group; p = 0.75) nor in SD durations (64 ± 27 vs. 69 ± 37 sec, p = 0.54). In separate experiments (n = 3), hypoxia was induced by decreasing inhaled O 2 to 10% and single SDs were induced under interleaved conditions of hypo-, normo-, and hypercapnia. No differences in SD duration were observed. In both normoxia and hypoxia experiments, however, mean arterial pressures were negatively correlated with SD durations (normoxia R2 = −0.29; hypoxia R2 = −0.61, p 's < 0.001). Our results suggest that any therapeutic benefit of elevated CO 2 therapy may be dependent on an acidic shift in pH or may only be observed in conditions of focal brain injury. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: The design, testing and clinical implementation of a simple quality assurance tool which allows quick and accurate identification of regions of data loss and data interpolation in 4DCT data sets is reported. Materials and methods: A 4DCT model, dependent on gantry rotation time and pitch, was developed to allow an understanding of the data collection and reconstruction processes. To test this model, 4DCT scans of a phantom were acquired using a Siemens SOMATOM Sensation 40 slice CT scanner. A radio-opaque rod mounted under the couch top was present during the phantom scans. Results: The model predicts that periodic regions of data loss occur when the respiration rate drops below a critical value. These results are verified by experimental data. Regions of data loss result in breaks in the imaged radio-opaque rod. Conclusions: Regions of data loss in 4DCT data sets can be difficult to detect. Mounting a radio-opaque rod under the couch top allows regions of data loss and data interpolation to be quickly assessed on a patient by patient basis. This quality assurance tool has been successfully implemented into clinical use. The results of this work have implications for quality assurance programmes for 4DCT scanning. [Copyright &y& Elsevier]

Summary: Australia is a climatically diverse country varying from a tropical climate in the north to arid central desert and grassland regions, and to temperate climates in the south. There are many viral infections found in Australia that are common to developed countries worldwide, but this article will focus on those that pose a special risk for travellers to Australia, especially the mosquito-borne viruses. The commonest are the members of the alphavirus genus, particularly Ross River virus and Barmah Forest virus, which cause predominantly arthralgia with or without fever or rash. Less frequent but more serious illness is seen with the encephalitic flaviviruses, Murray Valley encephalitis virus, and the Kunjin strain of West Nile virus. In addition dengue occurs intermittently on the northern part of Queensland, and in recent years Japanese encephalitis virus has been found in the Torres Strait Islands and the tip of far north Queensland. Also of interest, but with a much lower risk, are the bat-borne viruses, Hendra virus and Australian bat lyssavirus, that have caused a small number of human infections. However, it is important to remember that most tourists pass through other countries in the Asia/Pacific region on their way to and from Australia and may therefore have acquired infections prior to or after leaving Australia. [Copyright &y& Elsevier]

Abstract: When olfactory receptor neurons respond to odors, a depolarizing Cl− efflux is a substantial part of the response. This requires that the resting neuron accumulate Cl− against an electrochemical gradient. In isolated olfactory receptor neurons, the Na ++K+ +2Cl− cotransporter NKCC1 is essential for Cl− accumulation. However, in intact epithelium, a robust electrical olfactory response persists in mice lacking NKCC1. To determine whether NKCC1 is required for normal olfactory sensitivity, olfactory sensitivity was compared between knockout (KO) mice carrying a null mutation for NKCC1 and wild-type (WT) littermates. Using operant behavioral techniques, olfactory sensitivity was measured using a commercial liquid-dilution olfactometer. Detection thresholds for the simple odorants cineole, 1-heptanol, and 1-propanol were compared in KO and WT animals. Regardless of the stimulus conditions employed, no systematic differences in behavioral thresholds were evident between KO and WT animals. We conclude that NKCC1 is not required for normal olfactory sensitivity. [Copyright &y& Elsevier]

Abstract: Double-blinding is an important and widely implemented feature of clinical trials although its success is rarely assessed. In a randomized, placebo-controlled trial of tea tree oil, an aromatic essential oil, for the treatment of recurrent herpes labialis (RHL), or cold sores, deception was used to prevent volunteers from identifying their treatment allocation. Volunteers received placebo (n =102) or tea tree oil (n =112) ointment in preparation for their next episode of RHL and were told, falsely, that the aroma of the ointments had been changed to prevent identification of the treatment group. At the trial''s end, of the volunteers who had used their ointment and presented for treatment assessment (n =100), approximately 50% correctly guessed their treatment allocation (P =0.774). Amongst volunteers that had not presented for treatment assessment (n =114), 12 volunteers did not provide blinding data and 46 did not open their tube. For the 56 volunteers who opened their tube, less than half of those receiving tea tree oil (44.4%) and only a small proportion of those on placebo (17.2%) were able to correctly identify their treatment allocation. Among the volunteers that were not treated, the P-value was 0.083. This study showed that the ethical use of deception may provide effective blinding in challenging circumstances. [Copyright &y& Elsevier]

Abstract: Purpose: To compare the visibility of different manufacturers I-125, seeds, and to investigate the effect of differences in dosimetry on treatment planning. Materials and methods: Oncura Oncoseed, Oncura Echoseed, IBT Intersource, Bebig Isoseed and Nucletron Selectseed were investigated. The point dose at increasing distances from each seed type was calculated for three different angles; θ =0°, 45° and 90° (where θ =0° lies parallel to seed length). 10 patient plans were used to assess the effect of a change in dosimetry on treatment planning and quality of prostate and rectum implant indices such as Vp100, Vp200, Dp90, Vr100 and Vr69. All implant indices and dosimetry data were compared to Oncoseed. Visibility under X-ray, fluoroscopy, CT and MRI was investigated using prostate phantoms created in-house. Statistical significance was calculated using paired two-tailed t-tests. Results: Dosimetric analysis was carried out for seeds of the same source strength. Differences in dose increase closer to the centre of each source, with the largest changes occurring for the angle θ =0°. Selectseed and Isoseed seed types provide a consistently lower dose in all three directions. Changes to Vp100 are small and statistically insignificant for all seeds except Selectseed which shows a statistically significant decrease of 0.04% (p =0.02). Changes to Vp150 and Vp200 are statistically significant (p <0.01), with Intersource showing the greatest increase in both values. Selectseed shows a decrease in both Vp150 and Vp200. Echoseed shows an increase in both Vp150 and Vp200. Changes to D90 are statistically significant (p <0.01), with Intersource showing the greatest increase, followed by Isoseed then Echoseed. Selectseed shows a decrease in D90. For Vr100 there is no statistically significant change for any seed type. However, all seeds except Selectseed show a statistically significant increase in the value of Vr69, with Intersource showing the greatest increase. On fluoroscopy and X-ray images, Intersource seeds appear least visible, Echoseed and Oncoseed are similar, and Isoseed and Selectseed are most visible. Ultrasound greyscale beam profiles show that all seed images have a FWHM larger than the Oncoseed image. The CT greyscale beam profiles are similar for all seed images. The MRI signal voids are similar for all seed images except Intersource which shows a larger signal void. Conclusions: The greatest changes to point dose occur at very close distances to the seeds. Changing seed type may require a treatment replan to maintain satisfactory DVH criteria. Visibility on US and CT is similar, though it may vary on MRI, X-ray and fluoroscopy. [Copyright &y& Elsevier]

Abstract: Objective: The demanding behavioral changes for weight control to manage diabetes might contribute to lower quality of life (QOL). This research examines whether the demands of diet and exercise contribute to lower QOL among persons with diabetes. Methods: Data were from the Behavioral Risk Factor Surveillance System (BRFSS), which measures days in the last month for poor physical health, poor mental health, limited activity, pain, depression, stress, poor sleep, and high energy, as well as weight control efforts. Results: Respondents with diabetes averaged more impaired days on every measure of QOL. Neither efforts to control weight nor dieting were related to any measure. Exercise was associated with reductions in impaired days on all measures. Conclusions: Exercising to control weight had a powerful effect on reducing QOL differences while attempting to maintain or reduce weight, and dieting to do so had no effect. [Copyright &y& Elsevier]

Chemical consolidation may occur when a salt solution infiltrates into a clay soil. To date, most studies have considered solute diffusion alone, ignoring advective transport processes. This may be justified for some clays, however for other clays osmotic flows can be significant, and so require a careful analysis of solute advection. This paper considers the influence of solute advection on coupled chemical and mechanical consolidation of clays. The theoretical and numerical study considers both transient and steady-state solutions. It is found that solute advection can have a large effect on computed solute concentrations, excess pore water pressures, and settlements. The effects of including solute advection become increasingly important for osmotic efficiencies greater than 0.005 and when the ratio of chemical to mechanical coefficients of volume change become greater than 0.005. The differences in estimated responses of the clay, based on models with and without solute advection, can be as large as one order of magnitude. [Copyright &y& Elsevier]

Inhibitors of amyloid-β (Aβ) protein production have been widely pursued as a potential treatment for Alzheimer''s disease. Following the identification of a 5 μM screening hit, SAR was initiated using solid-phase synthetic techniques. Two series of α-hydroxy esters and ketones which are sub-micromolar inhibitors of Aβ production were identified. The most potent α-hydroxyketone identified is approximately 30-fold more potent than the initial lead. [Copyright &y& Elsevier]

When analyzing vitreal drug delivery, or the pharmacological effects of drugs on intraocular pressure, or when interpreting outflow facility measurements, it is generally accepted that the fluid in the vitreous humor is stagnant. It is accepted that for all practical purposes, the aqueous fluid exits the eye via anterior pathways only, and so there is negligible if any posteriorly directed flow of aqueous through the vitreous humor. This assumption is largely based on the interpretation of experimental data from key sources including Maurice (1957), Moseley (1984), Gaul and Brubaker (1986), Maurice (1987) and Araie et al. (1991). However, there is strong independent evidence suggesting there is a substantial fluid flow across the retinal pigment epithelium from key sources including Cantrill and Pederson (1984), Chihara and Nao-i, Tsuboi (1985), Dahrouj et al. (2014), Smith and Gardiner (2017) and Smith et al. (2019). The conflicting evidence creates a conundrum-how can both interpretations be true? This leads us to re-evaluate the evidence. We demonstrate that the data believed to be supporting no aqueous flow through the vitreous are in fact compatible with a significant normal aqueous flow. We identify strong and independent lines of evidence supporting fluid flow across the RPE, including our new outflow model for the eye. On balance it appears the current evidence favors the view that there is normally a significant aqueous flow across the RPE in vivo. This finding suggests that past and future analyses of outflow facility, interpretations of some drug distributions and the interpretation of some drug effects on eye tissues, may need to be revised. [ABSTRACT FROM AUTHOR]

This study presents a coupled cartilage contact model, in which the contact gap and cartilage tissue are modelled as two poroelastic systems, linked by pressure and normal flux continuity boundary conditions. Using a tibial plug under indentation as a proof-of-concept model, the predictions support the weeping lubrication theory under static compression. Specifically, the interstitial fluid would exude from the underlying cartilage into the contact gap to extend the mixed-mode duration by > 20-fold compared to a no fluid exudation counterpart. Moreover, the traditional contact model, that does not consider the contact gap and cartilage fluid exchange, potentially overestimates the interstitial fluid pressure compared to the proposed coupled model. Parametric studies suggest that the increasing viscosity of synovial fluid prolongs the gap fluid pressurisation, while increasing the asperity stiffness reduces the gap fluid pressure but increases contact gap height. • Coupled contact model considering contact gap and cartilage interaction. • Fluid would exude into the gap and extend mixed-mode duration. • Traditional contact model potentially overestimates the interstitial fluid pressure. • Asperity stiffness and synovial fluid viscosity influence the lubrication effect. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the effects of meteorological variations on the activity of influenza A and B in 11 sites across different climate regions.Methods: Daily numbers of laboratory-confirmed influenza A and B cases from 2011-2015 were collected from study sites where the corresponding daily mean temperature, relative humidity, wind speed and daily precipitation amount were used for boosted regression trees analysis on the marginal associations and the interaction effects.Results: Cold temperature was a major determinant that favored both influenza A and B in temperate and subtropical sites. Temperature-to-influenza A, but not influenza B, exhibited a U-shape association in subtropical and tropical sites. High relative humidity was also associated with influenza activities but was less consistent with influenza B activity. Compared with relative humidity, absolute humidity had a stronger association - it was negatively associated with influenza B activity in temperate zones, but was positively associated with both influenza A and B in subtropical and tropical zones.Conclusion: The association between meteorological factors and with influenza activity is virus type specific and climate dependent. The heavy influence of temperature on influenza activity across climate zones implies that global warming is likely to have an impact on the influenza burden. [ABSTRACT FROM AUTHOR]

This study focuses on the relationship between meniscectomy and osteochondral junction health, and their integrity on cartilage lubrication. Using a previously published multi-component joint computational model, we explored the impact of increasing degree of meniscectomy and osteochondral flow conductivity on joint lubrication. Results suggest a greater effect of meniscectomy on joint lubrication when the osteochondral junction is healthy. However, the impact is less pronounced when the osteochondral junction is already diseased due to compromised lubrication capability. This research provides a first-time quantitative analysis of this interaction, which highlights the importance of adequately evaluating the osteochondral junction's condition before meniscectomy surgery. It also suggests that reducing post-surgery activity level may be beneficial for patients with diseased junctions undergoing meniscectomy. [ABSTRACT FROM AUTHOR]

• Mice were subjected to experimental hypercapnia prior to TBI. • CO 2 exposure prior to TBI attenuates neurotrauma-elicited physiologic alterations. • Hypercapnia drives hippocampal transcriptional alterations independent of TBI. • CO 2 exposure prevents specific TBI-induced hippocampal transcriptional alterations. Acceleration/deceleration forces are a common component of various causes of mild traumatic brain injury (mTBI) and result in strain and shear forces on brain tissue. A small quantifiable volume dubbed the compensatory reserve volume (CRV) permits energy transmission to brain tissue during acceleration/deceleration events. The CRV is principally regulated by cerebral blood flow (CBF) and CBF is primarily determined by the concentration of inspired carbon dioxide (CO 2). We hypothesized that experimental hypercapnia (i.e. increased inspired concentration of CO 2) may act to prevent and mitigate the actions of acceleration/deceleration-induced TBI. To determine these effects C57Bl/6 mice underwent experimental hypercapnia whereby they were exposed to medical-grade atmospheric air or 5% CO 2 immediately prior to an acceleration/deceleration-induced mTBI paradigm. mTBI results in significant increases in righting reflex time (RRT), reductions in core body temperature, and reductions in general locomotor activity-three hours post injury (hpi). Experimental hypercapnia immediately preceding mTBI was found to prevent mTBI-induced increases in RRT and reductions in core body temperature and general locomotor activity. Ribonucleic acid (RNA) sequencing conducted four hpi revealed that CO 2 exposure prevented mTBI-induced transcriptional alterations of several targets related to oxidative stress, immune, and inflammatory signaling. Quantitative real-time PCR analysis confirmed the prevention of mTBI-induced increases in mitogen-activated protein kinase kinase kinase 6 and metallothionein-2. These initial proof of concept studies reveal that increases in inspired CO 2 mitigate the detrimental contributions of acceleration/deceleration events in mTBI and may feasibly be translated in the future to humans using a medical device seeking to prevent mTBI among high-risk groups. [ABSTRACT FROM AUTHOR]

Dogs are deployed for the detection of a wide variety of chemical stimuli. Despite their wide use, little basic research has explored canine olfactory generalization and discrimination. In the present study, we assessed canine odor discrimination amongst a series of chemically-related aliphatic alcohols. Domestic dogs were trained to discriminate 1-pentanol from air in a two-choice operant discrimination procedure until reaching an 85% accuracy criterion. In a series of transfer tasks, we assessed dogs’ generalization and discrimination between related odorants by replacing the S − stimulus with an alcohol related to pentanol, differing only in the length of the carbon chain. Dogs showed an increase in discrimination performance with an increase in the difference in the number of carbon atoms between pentanol and the comparison alcohol ( p < 0.001). These results indicate that this graded series of alcohols may be a useful stimulus set for studying olfactory generalization and discrimination processes in dogs, and that dogs show the same relationship between chemical similarity and discrimination performance as has been observed with humans, monkeys, honeybees, elephants, and rats. [ABSTRACT FROM AUTHOR]

Abstract: In engineering approaches, the electro-diffusive transport behavior of ions through charged porous media is often described by phenomenological theories, formulated on the observation scale of the macroscopic material, without considering the underlying physics on the particle scale. We propose a new approach, by implementing a generalized multiscale framework, based on the classical Poisson–Nernst–Planck theory, which is valid for both charged and uncharged porous media. A numerical upscaling scheme is employed for evaluation of the transport properties in the governing macroscopic equations. Macroscale estimates of the effective diffusion coefficients and of the effective fixed charge concentration are found based on the electrolyte background concentration and on the surface charge applied on the microscale. To demonstrate this new methodology, we implement the upscaling scheme for three different pore geometries: a linear cylindrical pore, a linear slit, and a spherical inclusion. For the chosen geometries and boundary conditions, we find a significant dependence of the effective macroscale properties on the magnitude of prescribed concentrations, the particle surface charge, and the shape of the pore space. Parametric studies reveal effective diffusion coefficients in charged porous media exceeding the corresponding self-diffusion coefficients by up to 34%. For a constant macroscopic concentration gradient, decreasing background concentrations result in a moderate increase of effective diffusion coefficients. The magnitude of the surface charge turns out to strongly influence the effective diffusion coefficients, that is increasing the magnitude of surface charge leads to significantly increased effective diffusion coefficients. These results suggest that rigorously considering electrochemical couplings will lead to a deeper understanding as to the origins of macroscopic experimental observations, and with future inclusion of effects such as cation exchange, to improved computer simulation-based modeling of ion transport through charged porous materials such as clay soils. [Copyright &y& Elsevier]

Abstract: It is generally accepted that RANKL is highly expressed in osteoblast precursor cells while OPG is highly expressed in mature osteoblasts, but to date no functional utility to the BMU has been proposed for this particular ligand–decoy–receptor expression profile. As discovered in the mid 90s, the RANK–RANKL–OPG signaling cascade is a major signaling pathway regulating bone remodeling. In this paper we study theoretically the functional implications of particular RANKL/OPG expression profiles on bone volume. For this purpose we formulate an extended bone–cell dynamics model describing functional behaviour of basic multicellular units (BMUs) responsible for bone resorption and formation. This model incorporates the RANK–RANKL–OPG signaling together with the regulating action of TGF-β on bone cells. The bone–cell population model employed here builds on the work of Lemaire et al. (2004) [1], but incorporates the following significant modifications: (i) addition of a rate equation describing changes in bone volume with time as the key ‘output function’ tracking functional behaviour of BMUs, (ii) a rate equation describing release of TGF-β from the bone matrix, (iii) expression of OPG and RANKL on both osteoblastic cell lines, and (iv) modified activator/repressor functions. Using bone volume as a functional selection criterion, we find that there is a preferred arrangement for ligand expression on particular cell types, and further, that this arrangement coincides with biological observations. We then investigate the model parameter space combinatorially, searching for preferred ‘groupings’ of changes in differentiation rates of various cell types. Again, a criterion of bone volume change is employed to identify possible ways of optimally controlling BMU responses. While some combinations of changes in differentiation rates are clearly unrealistic, other combinations of changes in differentiation rates are potentially functionally significant. Most importantly, the combination of parameter changes representing the signaling pathway for TGF-β gives a unique result that appears to have a clear biological rationale. The methodological approach for the investigation of model structure described here offers a theoretical explanation as to why TGF-β has its particular suite of biological effects on bone–cell differentiation rates. [Copyright &y& Elsevier]

2,3-Benzodiazepin-1,4-diones were designed as peptidomimetics at the carboxy terminus of hydroxyamides. Inhibition of brain Aβ production was improved by one of the compounds containing constrained modification. [Copyright &y& Elsevier]

The dramatic differences observed when comparing auditory neural responses to electrical and acoustic stimulation may illustrate one of the important mechanisms underlying the sometimes poor speech recognition abilities of individuals with cochlear implants. Recent research has suggested that the absence of a stochastic component in neural responses to electrical activation may be an important potential mechanism for this degradation in speech recognition performance. There are few psychophysical data, however, demonstrating that this stochastic behavior can be measured directly in implant subjects. In this study, variability in psychophysical threshold was investigated as a measure of the stochastic nature of the underlying neural response in human and non-human subjects implanted with intracochlear electrode arrays. Threshold data collected in both monopolar and bipolar stimulation modes at several phase durations from cat and human subjects are presented. The nature of the neural input/output curve suggests that threshold variability should increase as the slope of the input/output curve is decreased, i.e. as phase duration is increased. These predictions are confirmed by the pattern of psychophysical results measured experimentally in cat and human subjects. Furthermore, the data may suggest that subjects with higher threshold variability, i.e. a relatively greater stochastic component, are more likely to have higher speech recognition scores. [Copyright &y& Elsevier]

Foraging behaviour of Porcellio scaber was observed in laboratory arenas in which the spatial distribution of patches of high quality food (powdered dicotyledonous leaf litter) was varied within a matrix of lower quality food (powdered grass leaf litter). The hypotheses that feeding behaviour of isopods would vary with the degree of clumping of high quality food patches and with the density of conspecifics, were tested. In more clumped treatments, animals spend less time on high quality food and more on a low quality one. At higher densities more time was spent searching. This effect was more pronounced in clumped treatments, but negligible in homogeneous ones. The effects of variation in the spatial heterogeneity of high quality foods on the trade-off between searching costs and intake-rate benefits for saprophages are discussed in the context of predictions from optimal foraging theory for scenarios in which intake-rate maximisation is constrained by nutrient limitation. [Copyright &y& Elsevier]

In this report, we describe an azithromycin treatment failure in community-acquired pneumonia. During the first three days of azithromycin, the patient’s symptoms worsened, and she was subsequently admitted to the hospital. Blood cultures were positive for a penicillin-susceptible, macrolide-resistant S. pneumoniae. DNA sequencing revealed an A2059G mutation in domain V of the 23S rRNA. To our knowledge, this is the first clinical report of an azithromycin failure in the treatment of S. pneumoniae resistant to macrolides by this mechanism. [Copyright &y& Elsevier]

Emerging evidence suggests that aging is associated with a reduced ability to distinguish perceptually similar stimuli in one's environment. As the ability to accurately perceive and encode sensory information is foundational for explicit memory, understanding the neurobiological underpinnings of discrimination impairments that emerge with advancing age could help elucidate the mechanisms of mnemonic decline. To this end, there is a need for preclinical approaches that robustly and reliably model age-associated perceptual discrimination deficits. Taking advantage of rodents' exceptional olfactory abilities, the present study applied rigorous psychophysical techniques to the evaluation of discrimination learning in young and aged F344 rats. Aging did not influence odor detection thresholds or the ability to discriminate between perceptually distinct odorants. In contrast, aged rats were disproportionately impaired relative to young on problems that required discriminations between perceptually similar olfactory stimuli. Importantly, these disproportionate impairments in discrimination learning did not simply reflect a global learning impairment in aged rats, as they performed other types of difficult discriminations on par with young rats. Among aged rats, discrimination deficits were strongly associated with spatial learning deficits. These findings reveal a new, sensitive behavioral approach for elucidating the neural mechanisms of cognitive decline associated with normal aging. [ABSTRACT FROM AUTHOR]