Non-Gaussian Error Distribution of 7Li\rm{^{7}Li} Abundance Measurements

We construct the error distribution of $\rm{^{7}Li}$ abundance measurements for 66 observations (with error bars) used by Spite12 that give $\rm{A(Li)}=2.21 \pm 0.065$ (median and 1$\sigma$ symmetrized error). This error distribution is somewhat non-Gaussian, with larger probability in the tails than is predicted by a Gaussian distribution. The 95.4% confidence limits are 3.0$\sigma$ in terms of the quoted errors. We fit the data to four commonly used distributions: Gaussian, Cauchy, Student's t, and double exponential with the center of the distribution found with both weighted mean and median statistics. It is reasonably well described by a widened $n=8$ Student's $t$ distribution. Assuming Gaussianity, the observed A(Li) is 6.5$\sigma$ away from that expected from standard Big Bang nucleosynthesis given the $Planck$ observations Coc2014. Accounting for the non-Gaussianity of the observed A(Li) error distribution reduces the discrepancy to 4.9$\sigma$, which is still significant.Comment: 24 pages, 6 figures, 4 table

Anti-inflammatory activity of Punica granatum L. (Pomegranate) rind extracts applied topically to ex vivo skin

Coadministered pomegranate rind extract (PRE) and zinc (II) produces a potent virucidal activity against Herpes simplex virus (HSV); however, HSV infections are also associated with localised inflammation and pain. Here, the objective was to determine the anti-inflammatory activity and relative depth penetration of PRE, total pomegranate tannins (TPT) and zinc (II) in skin, ex vivo. PRE, TPT and ZnSO4 were dosed onto freshly excised ex vivo porcine skin mounted in Franz diffusion cells and analysed for COX-2, as a marker for modulation of the arachidonic acid inflammation pathway, by Western blotting and immunohistochemistry. Tape stripping was carried out to construct relative depth profiles. Topical application of PRE to ex vivo skin downregulated expression of COX-2, which was significant after just 6 h, and maintained for up to 24 h. This was achieved with intact stratum corneum, proving that punicalagin penetrated skin, further supported by the depth profiling data. When PRE and ZnSO4 were applied together, statistically equal downregulation of COX-2 was observed when compared to the application of PRE alone; no effect followed the application of ZnSO4 alone. TPT downregulated COX-2 less than PRE, indicating that tannins alone may not be entirely responsible for the anti-inflammatory activity of PRE. Punicalagin was found throughout the skin, in particular the lower regions, indicating appendageal delivery as a significant route to the viable epidermis. Topical application of TPT and PRE had significant anti-inflammatory effects in ex vivo skin, confirming that PRE penetrates the skin and modulates COX-2 regulation in the viable epidermis. Pomegranates have potential as a novel approach in ameliorating the inflammation and pain associated with a range of skin conditions, including cold sores and herpetic stromal keratitis

Policy and Literature Review on the Effect Millennials Have on Vehicle Miles Traveled, Greenhouse Gas Emissions, and the Built Environment

Vehicle travel has reduced substantially across all demographics in the 2000’s, but millennials or young adults born from 1985-2000 stand out as the group that has reduced vehicle travel the most. This reduction of travel among millennials is known as the millennial effect. This policy and literature review discusses insights from recent policy reports and literature regarding the millennial effect and identifies the prominent themes and gaps in our knowledge. The first section reviews existing research on the millennial effect on vehicle miles traveled (VMT). The second section discusses the influence of the built environment on the travel and activities of the millennial generation. The third section highlights scenarios describing the millennials effect’s potential magnitude and identifies topics for consideration in future scenario planning efforts. The final section discusses the uncertainty that exists regarding the future behavior of millennials and their influence on VMT and greenhouse gas emissions

Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

Background There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions. Materials and methods PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit. Results Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution. Conclusions The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores

Morphological and hemodynamical alterations in brachial artery and cephalic vein. An image‐based study for preoperative assessment for vascular access creation

The current study aims to computationally evaluate the effect of right upper arm position on the geometric and hemodynamic characteristics of the brachial artery (BA) and cephalic vein (CV) and, furthermore, to present in detail the methodology to characterise morphological and hemodynamical healthy vessels. Ten healthy volunteers were analysed in two configurations, the supine (S) and the prone (P) position. Lumen 3D surface models were constructed from images acquired from a non-contrast MRI sequence. Then, the models were used to numerically compute the physiological range of geometric (n = 10) and hemodynamic (n = 3) parameters in the BA and CV. Geometric parameters such as curvature and tortuosity, and hemodynamic parameters based on wall shear stress (WSS) metrics were calculated with the use of computational fluid dynamics. Our results highlight that changes in arm position had a greater impact on WSS metrics of the BA by altering the mean and maximum blood flow rate of the vessel. Whereas, curvature and tortuosity were found not to be significantly different between positions. Inter-variability was associated with antegrade and retrograde flow in BA, and antegrade flow in CV. Shear stress was low and oscillatory shear forces were negligible. This data suggests that deviations from this state may contribute to the risk of accelerated intimal hyperplasia of the vein in arteriovenous fistulas. Therefore, preoperative conditions coupled with post-operative longitudinal data will aid the identification of such relationships

The contribution of δ subunit-containing GABAA receptors to phasic and tonic conductance changes in cerebellum, thalamus and neocortex

We have made use of the δ subunit-selective allosteric modulator DS2 (4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridine-3-yl benzamide) to assay the contribution of δ-GABAARs to tonic and phasic conductance changes in the cerebellum, thalamus and neocortex. In cerebellar granule cells, an enhancement of the tonic conductance was observed for DS2 and the orthosteric agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol). As expected, DS2 did not alter the properties of GABAA receptor-mediated inhibitory postsynaptic synaptic conductances (IPSCs) supporting a purely extrasynaptic role for δ-GABAARs in cerebellar granule cells. DS2 also enhanced the tonic conductance recorded from thalamic relay neurons of the visual thalamus with no alteration in IPSC properties. However, in addition to enhancing the tonic conductance DS2 also slowed the decay of IPSCs recorded from layer II/III neocortical neurons. A slowing of the IPSC decay also occurred in the presence of the voltage-gated sodium channel blocker TTX. Moreover, under conditions of reduced GABA release the ability of DS2 to enhance the tonic conductance was attenuated. These results indicate that δ-GABAARs can be activated following vesicular GABA release onto neocortical neurons and that the actions of DS2 on the tonic conductance may be influenced by the ambient GABA levels present in particular brain regions

In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection

Coadministration of pomegranate rind extract (PRE) and zinc (II) ions has recently been reported as a potential new topical treatment for Herpes simplex virus (HSV) infections. In the current work we examined the in vitro topical delivery of punicalagin (major phytochemical of PRE) and zinc from hydrogels across epithelial membranes that can become infected with HSV. Porcine epidermal, buccal and vaginal mucous membranes were excised and mounted in Franz diffusion cells and dosed with a simple hydrogel containing PRE and zinc sulphate (ZnSO4). The permeation of punicalagin and zinc were determined by HPLC and ICPMS respectively; punicalagin was also determined in the basal layers by reverse tape stripping. Receptor phases from the epidermal membrane experiment were also used to challenge HSV-1 in Vero host cells, and ex vivo porcine skin was used to probe COX-2 modulation. Punicalagin and zinc permeated each of the three test membranes, with significantly greater amounts of both delivered across the epidermal membrane. The amounts of punicalagin permeating the buccal and vaginal membranes were similar, although the amount of zinc permeating the vaginal membrane was comparatively very large – it is known that zinc interacts with vaginal mucosa. The punicalagin recovered by reverse tape stripping of the epidermal, buccal and vaginal membranes gave 0.47 ± 0.016, 0.45 ± 0.052 and 0.51 ± 0.048 nM cm− 2 respectively, and were statistically the same (p < 0.05). A 2.5 log reduction was achieved against HSV-1 using diffusion cell receptor phase, and COX-2 expression was reduced by 64% in ex vivo skin after 6 h. Overall, a hydrogel containing 1.25 mg mL− 1 PRE and 0.25 M ZnSO4 was able to topically deliver both the major bioactive compound within PRE and Zn (II) across all membranes and into the site specific region of Herpes simplex vesicular clusters, while maintaining potentiated virucidal and anti-inflammatory properties. This novel therapeutic system therefore has potential for the topical treatment of HSV infections

Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension

Objectives: Previous studies have demonstrated that high dose allopurinol is able to regress Left Ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well- controlled blood pressure but without established cardiovascular disease.Methods: We conducted a mechanistic proof-of-concept randomised, placebo controlled, double-blind trial of allopurinol (600mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress. Results: 72 patients were randomised into the trial. Mean baseline urate was 362.2 ± 96.7umol/L. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared to placebo (LV mass -0.37 ± 6.08 g vs -3.75 ± 3.89 g; p=0.012). Oxidative stress markers (Thiobarbituric acid reactive substances) were significantly higher in the allopurinol group vs placebo (0.26 ± 0.85uM vs -0.34 ± 0.83uM; p=0.007). Other markers of vascular function were not significantly different between the two groups.Conclusions: Treatment with high dose allopurinol in normo-uricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be due to an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.<br/