Evaluating the effects of minimum unit pricing in Scotland on the prevalence of harmful drinking: a controlled interrupted time series analysis.

OBJECTIVES: In May 2018, the Scottish Government introduced a minimum unit price (MUP) for alcohol of £0.50 (1 UK unit = 8 g ethanol) to reduce alcohol consumption, particularly among people drinking at harmful levels. This study aimed to evaluate MUP's impact on the prevalence of harmful drinking among adults in Scotland. STUDY DESIGN: This was a controlled interrupted monthly time series analysis of repeat cross-sectional data collected via 1-week drinking diaries from adult drinkers in Scotland (N = 38,674) and Northern England (N = 71,687) between January 2009 and February 2020. METHODS: The primary outcome was the proportion of drinkers consuming at harmful levels (>50 [men] or >35 [women] units in diary week). The secondary outcomes included the proportion of drinkers consuming at hazardous (≥14-50 [men] or ≥14-35 [women] units) and moderate (<14 units) levels and measures of beverage preferences and drinking patterns. Analyses also examined the prevalence of harmful drinking in key subgroups. RESULTS: There was no significant change in the proportion of drinkers consuming at harmful levels (ß = +0.6 percentage points; 95% confidence interval [CI] = -1.1, +2.3) or moderate levels (ß = +1.4 percentage points; 95% confidence interval = -1.1, +3.8) after the introduction of MUP. The proportion consuming at hazardous levels fell significantly by 3.5 percentage points (95% CI = -5.4, -1.7). There were no significant changes in other secondary outcomes or in the subgroup analyses after correction for multiple testing. CONCLUSIONS: Introducing MUP in Scotland was not associated with reductions in the proportion of drinkers consuming at harmful levels but did reduce the prevalence of hazardous drinking. This adds to previous evidence that MUP reduced overall alcohol consumption in Scotland and consumption among those drinking above moderate levels.

Nematic liquid crystal reorientation around multi-walled carbon nanotubes mapped via Raman microscopy.

We have studied the formation of topological defects in liquid crystal (LC) matrices induced by multiwalled carbon nanotubes (MWCNTs) and external electric fields. The defects are ascribable to a distortion of the LC molecular director in proximity of the MWCNT surface. The system is analyzed macroscopically using spectroscopic variable angle ellipsometry. Concurrently, confocal micro-Raman spectroscopy is used to study the system state at the microscale. This allows to acquire a three-dimensional, spatially-resolved map of the topological defect, determining scale length variations and orientation topography of the LC molecules around the MWCNT.

An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach.

Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastric juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses.

Toward hyperuniform disordered plasmonic nanostructures for reproducible surface-enhanced Raman spectroscopy.

We report on the self-assembling of clusters of gold-nanoparticles (Au-NPs) directed by the phase separation of poly(styrene)-b-poly(methylmethacrylate) (PS-b-PMMA) block-copolymer (BCP) on indium tin oxide coated glass, which induces the onset of vertical lamellar domains. After thermal evaporation of gold on BCP, Au-NPs of 4 nm are selectively included into PS-nanodomains by thermal annealing, and then clustered with large density of hot spots (> 10(4) µm(2)) in a random two-dimensional pattern. The resulting nanostructure exhibits near-hyperuniform long-range correlations. The consequent large degree of homogeneity of this isotropic plasmonic pattern gives rise to a highly reproducible Surface-Enhanced Raman Scattering (SERS) enhancement factor over the centimeter scale (std. dev. ∼ 10% over 0.25 cm(2)). We also discuss the application of a static electric field for modulating the BCP host morphology. The electric field induces an alignment of Au-NP clusters into ordered linear chains, exhibiting a stronger SERS activity, but reduced SERS spatial reproducibility.

[Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers]. / Estudio de biodisponibilidad relativa entre dos formulaciones orales de micofenolato mofetilo en voluntarios sanos.

BACKGROUND: The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. AIM: To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (Linfonex™) compared to the reference formulation (Cellcept™) to determine the bioequivalence between both formulations. MATERIAL AND METHODS: A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and área under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. RESULTS: The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. CONCLUSIONS: Linfonex™ 500 mg is bioequivalent to Cellcept™ 500 mg.

Diffusive mixing of polymers investigated by Raman microspectroscopy and microrheology.

Diffusive mixing in a model polymer blend of limited miscibility (i.e., the pair polydimethylsiloxane/polyisobutene) is investigated. The diffusion process is followed in the actual droplet-based microstructure of the polymer blend, as opposed to the ideal planar geometry used in previous studies (Brochard et al. Macromolecules 1983, 16, 1638; Composto et al. Nature 1987, 328, 234). In our experiments we combine Raman microspectroscopy and video particle-tracking microrheology. The first technique allows us to monitor local concentration of the two polymers with high spatial resolution both inside and outside a micrometer-size droplet of the dispersed phase. In addition, microrheology enables to follow how the local viscosity inside the droplet changes during the diffusion. The polymer viscosity inside the droplet is determined by video tracking the Brownian motion of a polystyrene bead microinjected into the droplet. The microspectroscopic and microrheological data are combined to estimate the concentration dependence of the monomer friction factor of the two species, which is a key parameter to calculate the interdiffusion coefficient D. Numerical calculations based on such concentration-dependent interdiffusion coefficient D and several alternative models of the polymer diffusion are compared to the experimental concentration profiles. A satisfactory agreement is found for the so-called "slow theory" (Brochard et al.). A phenomenological model improving the agreement of the model with the experimental data is also presented.

17beta-estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence.

We have found that 17beta-estradiol induces bcl-2 transcription in human breast cancer MCF-7 cells. To identify cis-acting elements involved in this regulation, we have analyzed hormone responsiveness of transiently transfected reporter constructs containing the bcl-2 major promoter (P(1)). Hormone inducibility was observed only when either of two sequences, located within the bcl-2 coding region and showing one and two mutations with respect to the consensus estrogen-responsive element, were inserted downstream from the P(1) promoter. Both sequences behaved as enhancers exclusively in cells expressing the estrogen receptor and were able to bind this receptor in in vitro assays. Transfections into MCF-7 cells of plasmids carrying a bcl-2 cDNA fragment which included these two elements revealed that their simultaneous presence resulted in an additive effect on reporter gene activity, whose size resembled the increase of endogenous bcl-2 mRNA level observed in untransfected cells after hormone treatment. Moreover, the identified elements were able to mediate up-regulation of bcl-2 expression by 17beta-estradiol, since exogenous bcl-2 mRNA was induced by hormone challenge of MCF-7 cells transiently transfected with a vector containing the bcl-2 coding sequence cloned under the control of a non-estrogen-responsive promoter. Finally, we show that hormone prevention of apoptosis, induced by incubating MCF-7 cells with hydrogen peroxide, was strictly related to bcl-2 up-regulation. Our results indicate that the bcl-2 major promoter does not contain cis-acting elements directly involved in transcriptional control by 17beta-estradiol and that hormone treatment inhibits programmed cell death in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements located within its coding region.

Work and heat probability distribution of an optically driven Brownian particle: theory and experiments.

We analyze the equations governing the evolution of distributions of the work and the heat exchanged with the environment by a manipulated stochastic system, by means of a compact and general derivation. We obtain explicit solutions for these equations for the case of a dragged Brownian particle in a harmonic potential. We successfully compare the resulting predictions with the outcomes of experiments, consisting of dragging a micron-sized colloidal particle through water with a laser trap.

[Analysis of certain oral health parameters in children with disabilities].

The first permanent molars which show the presence of congenital malocclusions, orthodontic treatment need and habits were studied in children with disabilities and healthy children. The examination covered 80 disabled children and 80 healthy ones (control group) of the age from 3 to 17 (mean age 10) years. Caries of the first permanent molars, bad habits and malocclusions were more common in children with disabilities than in healthy children. It was established that higher orthodontic treatment need was in children with disabilities who were less covered with orthodontic care.

Doppler-free spectroscopy of xenon in the mid-infrared using difference-frequency radiation.

We report on the first Doppler-free spectroscopy investigation of an atomic species, xenon, performed in the mid-infrared using difference-frequency radiation. The absorption saturated spectrum of the xenon 6p[3/2]2?5d[5/2]3 transition (2p6?3d'1 in Paschen notation) at 3.1076 microm was investigated using about 60 microwatts of cw narrowband radiation (Deltanu=50 kHz) generated by difference-frequency mixing in a periodically-poled Lithium Niobate crystal. A single frequency Ti:Sapphire laser (power 800 mW) and a monolithic diode-pumped Nd:YAG laser (300 mW) were used as pump and signal waves respectively. We used natural enriched xenon, which contains nine stable isotopes, two of which, 129Xe and 131Xe, exhibit a hyperfine structure owing to their nuclear spin. The small isotope displacements expected for this atom and the complex hyperfine structure of the odd isotopes make it difficult to fully resolve the recorded saturated-absorption spectra. In spite of this, we have been able to analyze the isolated 129Xe F''=5/2?F'=7/2 hyperfine component by means of first-derivative FM spectroscopy.

[Angle class I malocclusion in primary dentition and findings in permanent dentition--a follow-up study].

The aim of the study was to examine stability and changes in Angle Class I malocclusion from deciduous to permanent dentition in 168 subjects. All the subjects had Class I malocclusion in deciduous dentition, and were examined by the same orthodontist on two occasions during deciduous and permanent dentition. None of the subjects had received orthodontic therapy in the meantime. The results showed considerable changes from primary to permanent dentition. Crowding in primary dentition was retained in permanent dentition in 45.2% cases. In 16.2% cases it changed into normocclusion and 38.6% subjects developed other types of malocclusion. Open bite was retained in permanent dentition in 17.8% cases and in 17.8% subjects transformed into normocclusion. 64.4% subjects developed other types of malocclusion. Cross bite was retained in permanent dentition in 21.4% cases and in 28.6% subjects changed to normocclusion. Other types of malocclusion in permanent dentition developed in 50% subjects. In 30.8% of cases finding of premature loss of deciduous teeth was accompanied by extraction of some permanent teeth. Normocclusion was retained in 19.2% cases while 50% of children developed some type of malocclusion. Crowding, which was retained in permanent dentition in 45.2% cases, showed the highest degree of stability. Children with this type of anomaly in primary dentition displayed the highest frequency of total malocclusions (83.3% subjects). Out of all anomalies in primary dentition, cross bite most frequently switched to normal occlusion in permanent dentition (in 28.6% cases).

Difference-frequency-generator-based spectrometer at 3 mum for high-sensitivity C2H2 and H2O detection.

We detect acetylene and water-vapor lines by using a difference-frequency generator in the spectral region around 3 mm. Both C2H2 and H2O lines belong to fundamental vibrational bands and exhibit a line strength of the order of 10-20 cm/mol. Acetylene molecules were detected either by pure absorption or by first-derivative wavelength-modulation spectroscopy. The minimum detection sensitivity achieved for C2H2 in nitrogen was 4 ppb (parts in 109). Moreover, we discuss the effects of C2H2 pressure reduction in the presence of nitrogen in order to estimate systematic errors in the concentration measurements. Finally, we tested the accuracy of our spectrometer by detecting water vapor present as an impurity in a nitrogen cylinder at a nominal concentration of approximately 5 ppm.

Beyond cost: 'responsible purchasing' of managed care by employers.

We explore the extent of "responsible purchasing" by employers--the degree to which employers collect and use nonfinancial information in selecting and managing employee health plans. Most firms believe that they have some responsibility for assessing the quality of the health plans they offer. Some pay attention to plan characteristics such as the ability to provide adequate access to providers and services and scores on enrollee satisfaction surveys. A more limited but still notable number of firms take specific actions based on responsible purchasing information. Because of countervailing pressures, however, it is not clear whether or not the firms most involved in responsible purchasing are signaling a developing trend.

Incidence and duration of hospitalizations among persons with AIDS: an event history approach.

OBJECTIVE: To analyze hospitalization patterns of persons with AIDS (PWAs) in a multi-state/multi-episode continuous time duration framework. DATA SOURCES: PWAs on Medicaid identified through a match between the state's AIDS Registry and Medicaid eligibility files; hospital admission and discharge dates identified through Medicaid claims. STUDY DESIGN: Using a Weibull event history framework, we model the hazard of transition between hospitalized and community spells, incorporating the competing risk of death in each of these states. Simulations are used to translate these parameters into readily interpretable estimates of length of stay, the probability that a hospitalization will end in death, and the probability that a nonhospitalized person will be hospitalized within 90 days. PRINCIPAL FINDINGS: In multivariate analyses, participation in a Medicaid waiver program offering case management and home care was associated with hospital stays 1.3 days shorter than for nonparticipants. African American race and Hispanic ethnicity were associated with hospital stays 1.2 days and 1.0 day longer than for non-Hispanic whites; African Americans also experienced more frequent hospital admissions. Residents of the high-HIV-prevalence area of the state had more frequent admissions and stays two days longer than those residing elsewhere in the state. Older PWAs experienced less frequent hospital admissions but longer stays, with hospitalizations of 55-year-olds lasting 8.25 days longer than those of 25-year-olds. CONCLUSIONS: Much socioeconomic and geographic variability exists both in the incidence and in the duration of hospitalization among persons with AIDS in New Jersey. Event history analysis provides a useful statistical framework for analysis of these variations, deals appropriately with data in which duration of observation varies from individual to individual, and permits the competing risk of death to be incorporated into the model. Transition models of this type have broad applicability in modeling the risk and duration of hospitalization in chronic illnesses.

The role of electromyography in the diagnosis of velopharyngeal insufficiency: our experiences.

The subject of this study is the electromyographic investigation of the velopharyngeal sphincter structures. Seventy-five patients underwent examination, both patients with symptoms of velopharyngeal insufficiency and patients who were thought to have latent pathological sphincter changes based on local findings. A control group of 10 healthy examinees was also investigated. On the basis of electromyographic findings we divided patients into 2 groups: 57 patients without neuromuscular disorders and 18 patients with neuromuscular disorders of the velopharyngeal sphincter. Twelve patients from the latter group had acute, and 6 had chronic lesions of the velopharyngeal sphincter. Particular cases of illness within these 2 groups were investigated further. This study shows the usefulness of electromyography for diagnosing the exact causes of velopharyngeal insufficiency and for choosing the best approach to treatment.

Detection and spectroscopy of the v1 + v3 band of N2O by difference-frequency spectrometer at 3 microm.

We report the realisation of a laser spectrometer in the mid-infrared spectral region based on difference-frequency generation in a periodically poled LiNbO3 crystal. Tunable coherent radiation around 3 microm was produced by mixing a diode-pumped monolithic cw Nd-YAG laser and an injection-locked diode laser at 0.785 microm. High sensitivity N2O detection was demonstrated by observing pure absorption spectra of lines in the v1 + v3 combination band. We estimate a minimum detectable pressure of pure N2O of 1 x 10(-2) Pa with 0.9 m absorption path-length, corresponding to an absorbance of 3 x 10(-4). Nitrous oxide was also detected in presence of O2, N2 and air. Collisional broadening coefficients for the P(33) line at 3447.678 per cm are reported for N2O-N2 and N2O-O2 mixtures.

Effect of space radiation on expression of apoptosis-related genes in endometrial cells: a preliminary study.

In this paper we present some preliminary results on alteration of gene expression caused by radiation on human endometrial cells. To this purpose, we have studied the modulation of the expression of the bcl-2 gene family in two cell lines following irradiations with low energy protons and gamma-rays from a 60Co. The two epithelial cell strains, namely AN3Ca and HEC1B cells, both obtained from human neoplastic endometrial tissues, grow in culture and continue to maintain some differentiated functions typical of the original tissue. Indeed, these cells, that can be considered as representative of different stages of cellular transformation of endometrium. Because their epithelial nature and rapid growth, the expression of genes related to the maintenance of the cellular homeostasis (correction of omeostasis), as the pro and anti-apoptotic ones, is expected to be susceptible to changes in environment, including radiation. The effects have been evaluated in terms of both cell survival and changes in the expression of pro- and anti apoptotic proteins. Even though the data reported above can not be considered complete and/or definitive, nevertheless, in whole, they confirm that these cells may constitute a suitable model system to study, at molecular level, the effects of cosmic radiation on endometrium. Further observation, ensuing from these preliminary data, is that endometrial cells present different sensitivity to radiation in regard to its 'quality' and 'dosage', in accord to the original stage of differentiation.

Pharmacological suppression of rat distal colon chloride secretion requires two blockers.

Rat distal colon epithelium is frequently employed to assess the effect of natural and synthetic chemicals on chloride secretion. Inhibition of chloride secretion is often reported as the loop diuretic-sensitive portion of short-circuit current (Isc). The present work challenges the hypothesis that a loop diuretic alone is able to fully abolish chloride secretion. Isolated mucosa preparations were mounted in an Ussing chamber. The effects on short-circuit current of replacement of normal Ringer by a low (2.5 mmol/L) Cl solution and of blockers of basolateral Na, K, 2 Cl symport (bumetanide), apical Cl channels (diphenylamine-2-carboxylate, DPC), and anion exchange (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, SITS) alone and combined were assessed. Low Cl reversibly decreased Isc by 76%. In normal Ringer, bumetanide decreased Isc by 65%. SITS also had a significant effect at the serosal side, but not at the apical side, where DPC caused a 40% decrease. Chloride replacement, bumetanide and DPC, but not SITS, increased epithelial resistivity. Combined blockade of Na, K, 2 Cl symport and apical Cl channels, of Na, K, 2 Cl symport and anion antiport, or of anion antiport and apical Cl channels was needed to achieve reduction of short circuit current to the same extent seen with chloride replacement. Present results indicate that Isc of the unstimulated epithelium is mostly due to chloride secretion, and at least two blockers are required to abolish it. This fact should be taken into account in studies of chloride secretion-stimulating agents.