Reproducibility of acute steroid hormone responses in men to short-duration running

Purpose: Progressively overloading the body to improve physical performance may lead to detrimental states of overreaching/overtraining syndrome (OTS). Blunted cycling-induced cortisol and testosterone concentrations have been suggested to indicate overreaching following intensified-training periods. However, a running-based protocol is yet to be developed or demonstrated reproducible. This study develops two 30-min running protocols: (i) 50/70 (based on individualised physical capacity) and (ii) RPETP (self-paced) and measures the reproducibility of plasma cortisol and testosterone responses. Methods: Thirteen recreationally active, healthy males completed each protocol (50/70 and RPETP) on three occasions. Venous blood was drawn Pre-, Post- and 30 min Post-Exercise. Results: Cortisol was unaffected (both p > 0.05; 50/70: η2 = 0.090; RPETP: η2 = 0.252) whilst testosterone was elevated (both p < 0.05; 50/70: 35%, η2 = 0.714; RPETP: 42%, η2 = 0.892,) with low intra-individual coefficients of variation (CVi) as mean ± standard deviation (50/70: 7 ± 5%; RPETP: 12 ± 9%). Heart rate (50/70: ES = 0.39; RPETP: ES = -0.03), speed (RPETP: ES = -0.09) and rating of perceived exertion (50/70: ES = -0.06) were unchanged across trials (all CVi < 5%, p < 0.05). RPETP showed greater physiological strain (p < 0.01). Conclusions: Both tests elicited reproducible physiological and testosterone responses, but RPETP induced greater testosterone changes (likely due to increased physiological strain) and could therefore be considered a more sensitive tool to potentially detect OTS. Advantageously for the practitioner, RPETP does not require a priori exercise-intensity determination, unlike the 50/70, enhancing its integration into practice

Whole genome sequencing identifies putative associations between genomic polymorphisms and clinical response to the antiepileptic drug levetiracetam

In the context of pharmacogenomics, whole genome sequencing provides a powerful approach for identifying correlations between response variability to specific drugs and genomic polymorphisms in a population, in an unbiased manner. In this study, we employed whole genome sequencing of DNA samples from patients showing extreme response (n=72) and non-response (n=27) to the antiepileptic drug levetiracetam, in order to identify genomic variants that underlie response to the drug. Although no common SNP (MAF>5%) crossed the conventional genome-wide significance threshold of 5e-8, we found common polymorphisms in genes SPNS3, HDC, MDGA2, NSG1 and RASGEF1C, which collectively predict clinical response to levetiracetam in our cohort with ~91% predictive accuracy. Among these genes, HDC, NSG1, MDGA2 and RASGEF1C are potentially implicated in synaptic neurotransmission, while SPNS3 is an atypical solute carrier transporter homologous to SV2A, the known molecular target of levetiracetam. Furthermore, we performed gene- and pathway-based statistical analysis on sets of rare and low-frequency variants (MAF<5%) and we identified associations between the following genes or pathways and response to levetiracetam: a) genes PRKCB and DLG2, which are involved in glutamatergic neurotransmission, a known target of anticonvulsants, including levetiracetam; b) genes FILIP1 and SEMA6D, which are involved in axon guidance and modelling of neural connections; and c) pathways with a role in synaptic neurotransmission, such as WNT5A-dependent internalization of FZD4 and disinhibition of SNARE formation. In summary, our approach to utilise whole genome sequencing on subjects with extreme response phenotypes is a feasible route to generate plausible hypotheses for investigating the genetic factors underlying drug response variability in cases of pharmaco-resistant epilepsy

Ex vivo and In vivo Evaluation of Chitosan Coated Nanostructured Lipid Carriers for Ocular Delivery of Acyclovir

Background: Herpes keratitis is the most common infectious cause of blindness in the developed world. It may be treated by acyclovir (ACV), however this antiviral drug is poorly soluble with low ocular bioavailability requiring high and frequent dosing. Nanostructured lipid carriers (NLCs) were investigated to improve the ocular bioavailability of ACV by enhancing corneal penetration as well as prolonging the exposure of infected cells to the antiviral agent. Methods: Cell uptake studies, ex vivo tolerance and cell uptake efficacy as well as in vivo corneal permeation of the developed lipid based formulations were investigated. NLCs were fabricated by the hot microemulsion technique and coated with 0.5% w/v chitosan. NLCs were capable of increasing the cell uptake of encapsulated fluorescein and ACV as examined by fluorescence microscopy and high performance liquid chromatography (HPLC) respectively. Results: When entrapped in NLCs, the antiviral efficacy of ACV was increased by 3.5 fold after 24 hrs of exposure. The in vivo corneal permeation of the formulation was studied on Albino rabbits with NLCs capable of increasing the corneal bioavailability by 4.5 fold when compared to a commercially available ACV ophthalmic ointment. Conclusion: NLCs enhanced the ocular bioavailability and antiviral properties of ACV through cell internalisation, sustained release, and increased corneal permeation

Random volumes from matrices

We propose a class of models which generate three-dimensional random volumes, where each configuration consists of triangles glued together along multiple hinges. The models have matrices as the dynamical variables and are characterized by semisimple associative algebras A. Although most of the diagrams represent configurations which are not manifolds, we show that the set of possible diagrams can be drastically reduced such that only (and all of the) three-dimensional manifolds with tetrahedral decompositions appear, by introducing a color structure and taking an appropriate large N limit. We examine the analytic properties when A is a matrix ring or a group ring, and show that the models with matrix ring have a novel strong-weak duality which interchanges the roles of triangles and hinges. We also give a brief comment on the relationship of our models with the colored tensor models.Comment: 33 pages, 31 figures. Typos correcte

COP21 climate negotiators' responses to climate model forecasts

Policymakers involved in climate change negotiations are key users of climate science. It is therefore vital to understand how to communicate scientific information most effectively to this group. We tested how a unique sample of policymakers and negotiators at the Paris COP21 conference update their beliefs on year 2100 global mean temperature increases in response to a statistical summary of climate models' forecasts. We randomized the way information was provided across participants using three different formats similar to those used in Intergovernmental Panel on Climate Change reports. In spite of having received all available relevant scientific information, policymakers adopted such information very conservatively, assigning it less weight than their own prior beliefs. However, providing individual model estimates in addition to the statistical range was more effective in mitigating such inertia. The experiment was repeated with a population of European MBA students who, despite starting from similar priors, reported conditional probabilities closer to the provided models' forecasts than policymakers. There was also no effect of presentation format in the MBA sample. These results highlight the importance of testing visualization tools directly on the population of interest

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

Deep-level Transient Spectroscopy of GaAs/AlGaAs Multi-Quantum Wells Grown on (100) and (311)B GaAs Substrates

Si-doped GaAs/AlGaAs multi-quantum wells structures grown by molecular beam epitaxy on (100) and (311)B GaAs substrates have been studied by using conventional deep-level transient spectroscopy (DLTS) and high-resolution Laplace DLTS techniques. One dominant electron-emitting level is observed in the quantum wells structure grown on (100) plane whose activation energy varies from 0.47 to 1.3 eV as junction electric field varies from zero field (edge of the depletion region) to 4.7 × 106 V/m. Two defect states with activation energies of 0.24 and 0.80 eV are detected in the structures grown on (311)B plane. The Ec-0.24 eV trap shows that its capture cross-section is strongly temperature dependent, whilst the other two traps show no such dependence. The value of the capture barrier energy of the trap at Ec-0.24 eV is 0.39 eV

Using choir conducting to improve leadership practice

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