The impact of introducing alcohol-free beer options in bars and public houses on alcohol sales and revenue: A randomised crossover field trial.

AIMS: The study aimed to estimate the impact of introducing a draught alcohol-free beer, thereby increasing the relative availability of these products, on alcohol sales and monetary takings in bars and pubs in England. DESIGN: Randomised crossover field trial. SETTING: England. PARTICIPANTS: Fourteen venues that did not previously sell draught alcohol-free beer. INTERVENTION AND COMPARATOR: Venues completed two intervention periods and two control periods in a randomised order over 8 weeks. Intervention periods involved replacing one draught alcoholic beer with an alcohol-free beer. Control periods operated business as usual. MEASUREMENTS: The primary outcome was mean weekly volume (in litres) of draught alcoholic beer sold. The secondary outcome was mean weekly revenue [in GBP (£)] from all drinks. Analyses adjusted for randomised order, special events, season and busyness. FINDINGS: The adjusted mean difference in weekly sales of draught alcoholic beer was -20 L [95% confidence interval (CI) = -41 to +0.4], equivalent to a 4% reduction (95% CI = 8% reduction to 0.1% increase) in the volume of alcoholic draught beer sold when draught alcohol-free beer was available. Excluding venues that failed at least one fidelity check resulted in an adjusted mean difference of -29 L per week (95% CI = -53 to -5), equivalent to a 5% reduction (95% CI = 8% reduction to 0.8% reduction). The adjusted mean difference in weekly revenue was +61 GBP per week (95% CI = -328 to +450), equivalent to a 1% increase (95% CI = 5% decrease to 7% increase) when draught alcohol-free beer was available. CONCLUSIONS: Introducing a draught alcohol-free beer in bars and pubs in England reduced the volume of draught alcoholic beer sold by 4% to 5%, with no evidence of the intervention impacting net revenue.

Fostamatinib or Thrombopoietic Receptor Agonists for the Treatment of Chronic Immune Thrombocytopenia in Adult Patients: A Real-World Assessment of Safety, Effectiveness and Cost.

INTRODUCTION: Chronic immune thrombocytopenia purpura (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment is with corticosteroids. In patients who become resistant or intolerant to corticosteroids, the thrombopoietic agents (TPOs), consisting of romiplostim (ROM), eltrombopag (ELT) and avatrombopag (AVA) or the spleen tyrosine kinase inhibitor fostamatinib (FOS), are appropriate next lines of therapy. In this study, the comparative safety, effectiveness and cost of care between fostamatinib vs. the TPOs was evaluated in a real-world setting. METHODS: A retrospective analysis from 17 community hematology practices across the United States was conducted to identify adult ITP patients who received one of the four agents. Data collection consisted of patient demographics, disease characteristics, as well as number and type of prior treatments. From the first day until the end of treatment, data were also collected on platelet (PLT) counts, adverse events, the use of rescue IVIG, platelet transfusions and corticosteroids. Multivariable logistic regression analysis was used to compare PLT related endpoints between agents. RESULTS: A sample of 179 ITP patients who had received at least one of the four agents was identified. This resulted in a final sample of 51, 87, 127 and 44 patients who received FOS, ELT, ROM or AVA respectively. At month six, there were no significant differences between FOS vs. the TPOs in terms of the proportion of patients with the PLT count being ≥ 30 x 103/µL, ≥ 50 x 103/µL as well as the proportion of patients whose PLTs levels doubled relative to baseline. The frequency of thromboembolic events (TEs) was 3.9% in FOS patients compared to 9.2%, 4.7% and 11.4% in the ELT, ROM and AVA groups. The mean cost per patient with FOS was $99,209 (95%CI: $59,595 to $115,074) compared to $92,341 (95:CI$68,331 to $115,519), $108,482 (95%CI: $84,782 to $132,182) and $131,050 (95%CI: $83,327 to $179,897) for ELT, ROM or AVA respectively. CONCLUSIONS: In this real-world analysis, FOS was comparable to the TPOs in maintaining PLTs at clinically beneficial levels. Given these findings, the choice of therapy should be based on overall patient safety, preexisting risk factors for TEs and cost effectiveness.

Rheological design of thickened alcohol-based hand rubs.

The handleability and sensory perception of hand sanitisers by consumers affect the hygiene outcome. Spillage may result in under-dosing and poor sensory properties can lead to under-utilisation. We first propose four principles (low runoff, spreadability, smoothness and non-stickiness) for designing the rheology of thickened alcohol-based hand rubs with acceptable handleability and hand feel. We then evaluate a commercial hand gel and a variety of simplified formulations thickened with microgels (Carbopol 974P, Carbopol Ultrez 20 and Sepimax Zen), or linear polymers (Jaguar HP 120 COS), and evaluate them against these design criteria. All four additives provide acceptable spreadability by shear thinning to η ≈ 10 - 1 Pa s at γ ˙ ∼ 10 3 s - 1 . Either the finite yield stress conferred by the microgels ( σ y ≳ 10 Pa ) or the increase in low-shear viscosity provided by the linear polymer ( η ≳ 1 Pa s at γ ˙ ≲ 0.1 s - 1 ) give rise to acceptably low runoff. However, the formulation using the linear polymer shows a filament breakage time of τ b ≈ 1 s in capillary rheology, which may result in stickiness and therefore a less than optimal hand feel.

A Lifetime of Double Vision: A Case Report and Literature Review of Chronic Strabismus.

Strabismus is a condition preventing foveal alignment in normal gaze. Its effects can have long-standing impacts on physical, psychological, and social health. Multiple treatment options exist for strabismus such as surgery, optical correction, and vision therapy, however, treatment efficacy remains variable with little consensus on long-term impacts. Diplopia is a common side effect of the ocular misalignment secondary to strabismus and its treatment. When defining long-term success of treating strabismus, it is essential that visual sensory perception and binocular fusion has been integrated and remedied. Strabismus is complex and can be challenging to manage. To illustrate this, we report a 67-year-old female who presented with complications from long-term treatment of infantile strabismus. This case highlights differences in historical and contemporary strabismus treatments.

A method for quantifying pigment position in retinal pigment epithelium.

In wildtype mice, the pigment granules in the retinal pigment epithelium aggregate in the dark towards Bruch's membrane and disperse towards the photoreceptors in the light. We have developed a repeatable method amenable for quantifying pigment position in the RPE from wild type mice by estimating the population density of pigment granules, or pigment density, within 4 µm2 areas in the basal part of cells examined by transmission electron microscopy. To measure pigment position, 2 µm × 2 µm squares were aligned along the apical ends of the basal microvilli. The pigment granules within each 4 µm2 area were counted, and the average pigment density was calculated for each mouse. The average pigment density for light-adapted mice (n = 3 mice) was 1.3 pigment granules/µm2 (± 0.2 pigment granules/µm2). For dark-adapted wildtype mice (n = 3 mice), pigment density was 1.9 pigment granules/µm2 (± 0.3 pigment granules/µm2). Pigment density was statistically significantly different (p < 0.02) between light-adapted and dark-adapted mice, with pigment density higher in the dark-adapted mice. This method was implemented by four observers and their results were compared. No statistically significant differences were found in the measurements acquired by the different observers, illustrating the repeatability of the method.

Head-to-head competition does not affect pacing or performance in 1 km cycling time trials.

Previous research has shown enhanced performance and altered pacing behaviour in the presence of a virtual opponent during middle-distance cycling time trials with a duration of 2 min and longer. The purpose of this study was to determine whether these effects are also present in cycling time trials of shorter duration. Twelve physically active men completed three 1-km time trials. After a familiarisation trial (FAM), participants performed two experimental conditions: one without opponent (NO) and one with a virtual opponent (OP). Repeated-measures ANOVAs were used to assess differences in pacing and performance using power output and duration (p<0.05). No differences in mean finishing times (FAM: 91.5 ± 7.7 s; NO: 91.6 ± 6.4 s; OP: 90.9 ± 4.9 s; p=0.907) or power output (FAM: 382 ± 111 W; NO: 363 ± 80 W; OP: 367 ± 67; p=0.564) were found between experimental conditions. Furthermore, no differences in pacing profiles between experimental conditions were found (p=0.199). Similarly, rate of perceived exertion did not differ between experimental conditions at any moment (p=0.831). In conclusion, unlike events of a more prolonged duration (>2 min), the presence of an opponent did not affect participants' pacing behaviour in short duration 1-km time trials.

What is the role of dehydroepiandrosterone in gynecologic practice?

In small clinical trials, dehydroepiandrosterone (DHEA) has been found to relieve symptoms associated with postmenopausal conditions and infertility in women. DHEA may provide a cost-effective alternative to typical hormone therapies. Because of a lack of long-term and large-scale studies, only intravaginal DHEA supplementation is approved and recommended for treatment. Further investigation of DHEA supplementation is needed and encouraged to determine its safety and effectiveness.

High-throughput characterisation of bull semen motility using differential dynamic microscopy.

We report a high-throughput technique for characterising the motility of spermatozoa using differential dynamic microscopy. A movie with large field of view (∼10mm2) records thousands of cells (e.g. ≈ 5000 cells even at a low cell density of 20 × 106 cells/ml) at once and yields averaged measurements of the mean ([Formula: see text]) and standard deviation (σ) of the swimming speed, head oscillation amplitude (A0) and frequency (f0), and the fraction of motile spermatozoa (α). Interestingly, we found that the measurement of α is facilitated because the swimming spermatozoa enhance the motion of the non-swimming population. We demonstrate the ease and rapidity of our method by performing on-farm characterisation of bull spermatozoa motility, and validate the technique by comparing laboratory measurements with tracking. Our results confirm the long-standing theoretical prediction that [Formula: see text] for swimming spermatozoa.

PKC-ε pseudosubstrate and catalytic activity are necessary for membrane delivery during IgG-mediated phagocytosis.

In RAW 264.7 cells, PKC-ε regulates FcγR-mediated phagocytosis. BMDM behave similarly; PKC-ε concentrates at phagosomes and internalization are reduced in PKC-ε⁻/⁻ cells. Two questions were asked: what is the role of PKC-ε? and what domains are necessary for PKC-ε concentration? Function was studied using BMDM and frustrated phagocytosis. On IgG surfaces, PKC-ε⁻/⁻ macrophages spread less than WT. Patch-clamping revealed that the spreading defect is a result of the failure of PKC-ε⁻/⁻ macrophages to add membrane. The defect is specific for FcγR ligation and can be reversed by expression of full-length (but not the isolated RD) PKC-ε in PKC-ε⁻/⁻ BMDM. Thus, PKC-ε function in phagocytosis requires translocation to phagosomes and the catalytic domain. The expression of chimeric PKC molecules in RAW cells identified the εPS as necessary for PKC-ε targeting. When placed into (nonlocalizing) PKC-δ, εPS was sufficient for concentration, albeit to a lesser degree than intact PKC-ε. In contrast, translocation of δ(εPSC1B) resembled that of WT PKC-ε. Thus, εPS and εC1B cooperate for optimal phagosome targeting. Finally, cells expressing εK437W were significantly less phagocytic than their PKC-ε-expressing counterparts, blocked at the pseudopod-extension phase. In summary, we have shown that εPS and εC1B are necessary and sufficient for targeting PKC-ε to phagosomes, where its catalytic activity is required for membrane delivery and pseudopod extension.

Self-organization of particles with planar surface anchoring in a cholesteric liquid crystal.

We present birefringence and fluorescence confocal microscopy studies of melamine particles in a liquid-crystalline host solvent. The liquid crystal has a cholesteric phase at room temperature with a helical pitch that can be modified by changing the composition. The pitch employed here is always less than the particle diameter (3 microm). We demonstrate via birefringence that the mesogens preferentially anchor flat at the melamine surface. Via studies in a sample cell with aligning surfaces we show that although the particles form chains in a nematic liquid crystal they organize in 2D plates in a cholesteric. Fluorescence confocal microscopy and particle location analysis are used to determine the radial distribution function and to evaluate the particle aggregation number as a function of pitch length. We discuss possible explanations for the self-organization.

Electrostatic charging of nonpolar colloids by reverse micelles.

Colloids dispersed in a nonpolar solvent become charged when reverse micelles are added. We study the charge of individual sterically stabilized poly(methyl methacrylate) spheres dispersed in micellar solutions of the surfactants sodium bis(2-ethyl 1-hexyl) sulfosuccinate [AOT], zirconyl 2-ethyl hexanoate [Zr(Oct)2], and a copolymer of poly(12-hydroxystearic acid)-poly(methyl methacrylate) [PHSA-PMMA]. Although the sign of the particle charge is positive for Zr(Oct)2, negative for AOT, and essentially neutral for PHSA-PMMA, the different micellar systems display a number of common features. In particular, we demonstrate that over a wide range of concentrations the particle potential is a constant, independent of the number of micelles added and independent of the colloid size. A simple thermodynamic model, in which the particle charge is generated by the competitive adsorption of both positive and negative micelles, is in good agreement with the experimental data.

Characterization of microparticles with driven optical tweezers.

We discuss how actively-driven optical tweezers may be used to characterize Brownian microparticles. Two experiments are described in detail. We follow the thermal fluctuations of a charged particle in an oscillatory electric field and demonstrate that charges as low as a few elementary charges can be measured accurately and reproducibly. Secondly, we measure the orientational dynamics of a trapped rotating droplet and use circular polarimetry within optical tweezers to determine in situ birefringence.

Direct measurement of the effective charge in nonpolar suspensions by optical tracking of single particles.

The authors develop an ultrasensitive method for the measurement of the charge carried by a colloidal particle in a nonpolar suspension. The technique uses the phenomenon of the resonance of a particle held in an optical tweezer trap and driven by a sinusoidal electric field. The trapped particle forms a strongly damped harmonic oscillator whose fluctuations are a function of gamma, the ratio of the root-mean-square average of the electric and thermal forces on the particle. At low applied fields (gamma<<1) the particle is confined to the optical axis, while at high fields (gamma>>1) the probability distribution of the particle is double peaked. The periodically modulated thermal fluctuations are measured with nanometer sensitivity using an interferometric position detector. Charges, as low as a few elementary charges, can be measured with an uncertainty of about 0.25 e. This is significantly better than previous techniques and opens up new possibilities for the study of nonpolar suspensions.

Laser manipulation in liquid crystals: an approach to microfluidics and micromachines.

Laser trapping of particles in three dimensions can occur as a result of the refraction of strongly focused light through micrometre-sized particles. The use of this effect to produce laser tweezers is extremely common in fields such as biology, but it is only relatively recently that the technique has been applied to liquid crystals (LCs). The possibilities are exciting: droplets of LCs can be trapped, moved and rotated in an isotropic fluid medium, or both particles and defects can be trapped and manipulated within a liquid crystalline medium. This paper considers both the possibilities. The mechanism of transfer of optical angular momentum from circularly polarized light to small droplets of nematic LCs is described. Further, it is shown that droplets of chiral LCs can be made to rotate when illuminated with linearly polarized light and possible mechanisms are discussed. The trapping and manipulation of micrometre-sized particles in an aligned LC medium is used to provide a measure of local shear viscosity coefficients and a unique test of theory at low Ericksen number in LCs.

Measurement of effective temperatures in an aging colloidal glass.

We study the thermal fluctuations of an optically confined probe particle, suspended in an aging colloidal suspension, as the suspension transforms from a viscous liquid into an elastic glass. The micron-sized bead forms a harmonic oscillator. By monitoring the equal-time fluctuations of the tracer, at two different laser powers we determine the temperature of the oscillator, T(o). In the ergodic liquid the temperatures of the oscillator and its environment are equal, while in contrast, in a nonequilibrium glassy phase we find that T(o) substantially exceeds the bath temperature.