Effect of food on absorption of lomefloxacin

Twelve subjects participated in an open-label, single-dose, balanced three-way crossover study in which the absorptions of lomefloxacin were compared following (i) an overnight fast, (ii) a carbohydrate meal, and (iii) a high-fat meal. The time to peak concentration of lomefloxacin was delayed, but peak concentration in plasma and amount of drug absorbed were unchanged following both meals

A modern approach to the Heckel Equation: The effect of compaction pressure on the yield pressure of ibuprofen and its sodium salt

Despite being heavily criticised in the literature the most widely used and accepted compaction equation is the Heckel equation proposed by Heckel in 1961. Its presence in literature for 55 years is due to the ease in which it can distinguish between plastic and brittle materials. Achieving the correct balance of plastic and brittle materials in a formulation is critical to ensure adequate tablet strength is achieved therefore classifying materials using the Heckel equation is attractive. Despite the importance of this understanding, especially in the design and manufacture of direct compression formulations, there are no set analytical testing standards or materials classification guidelines. Instead many workers have attempted to develop techniques for the measurement and classification of a materials deformation but there is still confusion and contradiction present in this field. In this study we repot on report the effect of compaction pressure on the yield pressure of ibuprofen and its sodium salt. Ibuprofen and its sodium salt were selected as models for study due to the availability of comparative literature yield pressure values. The reported variation in yield pressure can be significant e.g, ibuprofen which has literature values of 21-1139 MPa. This study proposes an approach to determine yield pressure from the Heckel equation using a linear regression method. The full linear regression methodology utilised is described and is used to report the yield pressure of ibuprofen and its sodium salt dihydrate. This technique reveals the most representative compaction pressure in order to derive yield pressure to be 121 MPa. The yield pressure of ibuprofen and its sodium salt have been shown to increase with increasing compaction pressure. The reported values lie between 52-78 MPa for ibuprofen and 48-75 MPa for ibuprofen sodium dihydrate. The slightly lower reported yield pressure values for ibuprofen sodium suggest increased plasticity which could be attributed to the water contained within the structure acting as a plasticiser

Uniaxial compression of single crystal and polycrystalline tantalum

A series of compression experiments characterising the elastic-plastic response of single crystal and polycrystalline tantalum from quasi-static to intermediate strain-rates (10^−3 – 10^3 s−1) over a range of temperatures (233–438 K) are reported in this paper. The single crystal experiments show significant differences in the response of the three principle crystal orientations of tantalum in terms of yield, work hardening and ultimate deformed shapes. Modelling is undertaken using a dislocation mechanics based crystal plasticity finite element model giving insight into the underlying microscopic processes that govern the macroscopic response. The simulations show the importance of the dislocation mobility relations and laws governing the evolution of the mobile dislocation density for capturing the correct behaviours. The inclusion of the twinning/anti-twinning asymmetry is found to influence [100] orientation most strongly, and is shown to be critical for matching the relative yield strengths. In general the simulations are able to adequately match experimental trends although some specific details such as exact strain hardening evolution are not reproduced suggesting a more complex hardening model is required. 3D finite element simulations approximating the tests are also undertaken and are able to predict the final deformed sample shapes well once the twinning/anti-twinning asymmetry is included (particularly for the [100] orientation). The polycrystalline data in both as-received and cold rolled conditions shows the initial yield strength is highest and work hardening rate is lowest for the cold-rolled material due to the increase in mobile dislocation density caused by the prior work. The general behavioural trends with temperature and strain-rate of the polycrystalline materials are reproduced in the single crystal data however the specific form of stress versus strain curves are significantly different. This is discussed in terms of the similar active slip systems in polycrystalline material to high symmetry single crystals but with the significant added effect of grain boundary interactions

Further education improves cognitive reserve and triggers improvement in selective cognitive functions in older adults: The Tasmanian Healthy Brain Project

Introduction The strong link between early-life education and subsequent reduced risk of dementia suggests that education in later life could enhance cognitive function and may reduce age-related cognitive decline and protect against dementia. Methods Episodic memory, working memory, executive function, and language processing performances were assessed annually over 4 years in 359 healthy older adults who attended university for a minimum of 12 months (intervention) and were compared against 100 healthy adult controls. Results Multiple group latent growth curve modeling revealed a significant improvement in language processing capacity over time in the intervention group. No changes were detected for episodic memory, working memory, or executive function. Discussion These results suggest that complex mental stimulation resulting from late-life further education results in improved crystallized knowledge but no changes to fluid cognitive functions. © 2017 The Author

Dark Matter Direct Detection Signals inferred from a Cosmological N-body Simulation with Baryons

We extract at redshift z=0 a Milky Way sized object including gas, stars and dark matter (DM) from a recent, high-resolution cosmological N-body simulation with baryons. Its resolution is sufficient to witness the formation of a rotating disk and bulge at the center of the halo potential. The phase-space structure of the central galactic halo reveals the presence of a dark disk component, that is co-rotating with the stellar disk. At the Earth's location, it contributes to around 25% of the total DM local density, whose value is rho_DM ~ 0.37 GeV/cm^3. The velocity distributions also show strong deviations from pure Gaussian and Maxwellian distributions, with a sharper drop of the high velocity tail. We give a detailed study of the impact of these features on the predictions for DM signals in direct detection experiments. In particular, the question of whether the modulation signal observed by DAMA is or is not excluded by limits set by other experiments (CDMS, XENON and CRESST...) is re-analyzed and compared to the case of a standard Maxwellian halo, in both the elastic and the inelastic scattering scenarios. We find that the compatibility between DAMA and the other experiments is improved. In the elastic scenario, the DAMA modulation signal is slightly enhanced in the so-called channeling region, as a result of several effects. For the inelastic scenario, the improvement of the fit is mainly attributable to the departure from a Maxwellian distribution at high velocity.Comment: 39 page

Constraints on Decaying Dark Matter from Fermi Observations of Nearby Galaxies and Clusters

We analyze the impact of Fermi gamma-ray observations (primarily non-detections) of selected nearby galaxies, including dwarf spheroidals, and of clusters of galaxies on decaying dark matter models. We show that the fact that galaxy clusters do not shine in gamma rays puts the most stringent limits available to-date on the lifetime of dark matter particles for a wide range of particle masses and decay final states. In particular, our results put strong constraints on the possibility of ascribing to decaying dark matter both the increasing positron fraction reported by PAMELA and the high-energy feature in the electron-positron spectrum measured by Fermi. Observations of nearby dwarf galaxies and of the Andromeda Galaxy (M31) do not provide as strong limits as those from galaxy clusters, while still improving on previous constraints in some cases.Comment: 27 pages, 5 figures, submitted to JCAP, revised version with some additions and correction

Increased end-expiratory pressures improve lung function in near-term newborn rabbits with elevated airway liquid volume at birth

Approximately 53% of near-term newborns admitted to intensive care experience respiratory distress. These newborns are commonly delivered by cesarean section and have elevated airway liquid volumes at birth, which can cause respiratory morbidity. We investigated the effect of providing respiratory support with a positive end-expiratory pressure (PEEP) of 8 cmH(2)O on lung function in newborn rabbit kittens with elevated airway liquid volumes at birth. Near-term rabbits (30 days; term = 32 days) with airway liquid volumes that corresponded to vaginal delivery (similar to 7 mL/kg, control, n = 11) or cesarean section (similar to 37 mL/kg; elevated liquid (EL), n = 11] were mechanically ventilated (tidal volume= 8 mL/kg). The PEEP was changed after lung aeration from 0 to 8 to 0 cmH(2)O (control, n = 6; EL, n = 6), and in a separate group of kittens, PEEP was changed after lung aeration from 8 to 0 to 8 cmH(2)O (control, n = 5; EL, n = 5). Lung function (ventilator parameters, compliance, lung gas volumes, and distribution of gas within the lung) was evaluated using plethysmography and synchrotron-based phase-contrast X-ray imaging. EL kittens initially receiving 0 cmH(2)O PEEP had reduced functional residual capacities and lung compliance, requiring higher inflation pressures to aerate the lung compared with control kittens. Commencing ventilation with 8 cmH(2)O PEEP mitigated the adverse effects of EL, increasing lung compliance, functional residual capacity, and the uniformity and distribution of lung aeration, but did not normalize aeration of the distal airways. Respiratory support with PEEP supports lung function in near-term newborn rabbits with elevated airway liquid volumes at birth who are at a greater risk of suffering respiratory distress.NEW & NOTEWORTHY Term babies born by cesarean section have elevated airway liquid volumes, which predisposes them to respiratory distress. Treatments targeting molecular mechanisms to clear lung liquid are ineffective for term newborn respiratory distress. We showed that respiratory support with an end-expiratory pressure supports lung function in near-term rabbits with elevated airway liquid volumes at birth. This study provides further physiological understanding of lung function in newborns with elevated airway liquid volumes at risk of respiratory distress.Developmen

Higher CPAP levels improve functional residual capacity at birth in preterm rabbits

BACKGROUND: Preterm infants are commonly supported with 4-8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC).METHODS: Preterm rabbits delivered at 29/32 days (similar to 26-28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing similar to 2 cm H2O/min) for up to 10 min after birth.RESULTS: FRC was lower in the 0 (6.8 (1.0-11.2) mL/kg) and 5 (10.1 (1.1-16.8) mL/kg) compared to the 15 (18.8 (10.9-22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates.CONCLUSION: In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O.Developmen

TeV Symmetry and the Little Hierarchy Problem

Constraints from precision electroweak measurements reveal no evidence for new physics up to 5 - 7 TeV, whereas naturalness requires new particles at around 1 TeV to address the stability of the electroweak scale. We show that this "little hierarchy problem" can be cured by introducing a symmetry for new particles at the TeV scale. As an example, we construct a little Higgs model with this new symmetry, dubbed T-parity, which naturally solves the little hierarchy problem and, at the same time, stabilize the electroweak scale up to 10 TeV. The model has many important phenomenological consequences, including consistency with the precision data without any fine-tuning, a stable weakly-interacting particle as the dark matter candidate, as well as collider signals completely different from existing little Higgs models, but rather similar to the supersymmetric theories with conserved R-parity.Comment: 15 pages, 1 figure; v.2: typos corrected and various minor modifications/expansions on the presentations. now 16 pages and 1 figure. version to appear on JHE

LB01: Cell Salvage during Caesarean Section: A Randomised Controlled Trial (The SALVO Trial)

Objective Excessive haemorrhage at caesarean section requires the use of donor (allogeneic) blood transfusion. The SALVO trial assessed whether the routine use of cell salvage during caesarean section can reduce the need for donor blood transfusion. Study Design We conducted a randomised controlled trial (26 UK obstetric units; June 2013 through April 2016) of routine cell salvage use (intervention) vs. current standard of care without routine salvage use (control) in caesarean section among women at risk of haemorrhage. We used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2ml in RhD-negative women with RhD-positive baby (one of the secondary outcomes) between groups. Results Of 3028 women randomised, 2990 were analysed (after exclusions for vaginal delivery or hospital transfer after randomisation). Of 1498 assigned to intervention, 95.6% had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) vs. 3.9% of 1492 assigned to control. Donor blood transfusion rates were lower in the intervention group than in control (2.5% vs. 3.5%, adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01). No case of amniotic fluid embolism was observed. Fetomaternal haemorrhage was higher with intervention vs. control (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14). Conclusion There was modest evidence for an effect of routine use of cell salvage during caesarean section on donor blood transfusion. The increased fetomaternal haemorrhage emphasises the need for adherence to guidance on anti-D prophylaxis and for research on risks of alloimmunisation to RhD and other red cell antigens following cell salvage. (Funder: UK National Institute of Health Research Health Technology Assessment programme, ISRCTN66118656)