Enabling access to new WHO essential medicines: the case for nicotine replacement therapies

Nicotine replacement therapies (NRT) are powerful tools for the successful treatment of nicotine addiction and tobacco use. The medicines are clinically effective, supported by the Framework Convention on Tobacco Control, and are now World Health Organization-approved essential medicines. Enabling global access to NRT remains a challenge given ongoing confusion and misperceptions about their efficacy, cost-effectiveness, and availability with respect to other tobacco control and public health opportunities. In this commentary, we review existing evidence and guidelines to make the case for global access to NRT highlighting the smoker's right to access treatment to sensibly address nicotine addiction

Novel Cascaded Ultra Bright Pulsed Source of Polarization Entangled Photons

A new ultra bright pulsed source of polarization entangled photons has been realized using type-II phase matching in spontaneous parametric down conversion process in two cascaded crystals. The optical axes of the crystals are aligned in such a way that the extraordinarily (ordinarily) polarized cone from one crystal overlaps with the ordinarily (extraordinarily) polarized cone from the second crystal. This spatial overlapping removes the association between the polarization and the output angle of the photons that exist in a single type-II down conversion process. Hence, entanglement of photons originating from any point on the output cones is possible if a suitable optical delay line is used. This delay line is particularly simple and easy to implement.Comment: 8 pages 8 figure

Baseline corticosterone does not reflect iridescent plumage traits in female tree swallows

The production of high quality secondary sexual traits can be constrained by trade-offs in the allocation of energy and nutrients with other metabolic activities, and is mediated by physiological processes. In birds, the factors influencing male plumage quality have been well studied; however, factors affecting female plumage quality are poorly understood. Furthermore, it remains uncertain which physiological traits mediate the relationship between body condition and ornaments. In this three-year study of after-second-year female tree swallows (Tachycineta bicolor), we investigated (1) the relationship between baseline corticosterone near the end of the brood-rearing period (CORTBR) and feather colour characteristics (hue, saturation, brightness) the following year, and (2) the relationship between baseline corticosterone measured during incubation (CORTI) and brood rearing (CORTBR), and feather colour in the same year. To control for reproductive effort, we included reproductive parameters as covariates in all analyses. In this first study between CORT and the plumage colour characteristics of a species bearing iridescent feathers, we did not find any relationship between CORTBR and the colour of subsequently-produced feathers, nor did we find any relationship between CORT and the colour of feathers displayed during that breeding season. If CORT levels at the end of breeding carry over to influence the immediately subsequent moult period as we expect, our results generally indicate that structural plumage quality may not be as sensitive to circulating CORT levels compared to carotenoid-based colouration. Future studies, particularly those employing experimental manipulations of CORT during moult in species with iridescent traits, are necessary to fully determine the role glucocorticoids play in mediating the quality of secondary sexual characteristics

Parallel Evaluation of Multi-join Queries

A number of execution strategies for parallel evaluation of multi-join queries have been proposed in the literature. In this paper we give a comparative performance evaluation of four execution strategies by implementing all of them on the same parallel database system, PRISMA/DB. Experiments have been done up to 80 processors. These strategies, coming from the literature, are named: Sequential Parallel, Synchronous Execution, Segmented Right-Deep, and Full Parallel. Based on the experiments clear guidelines are given when to use which strategy. This is an extended abstract; the full paper appeared in Proc. ACM SIGMOD'94, Minneapolis, Minnesota, May 24–27, 199

Optic-nerve-transmitted eyeshine, a new type of light emission from fish eyes

Background: Most animal eyes feature an opaque pigmented eyecup to assure that light can enter from one direction only. We challenge this dogma by describing a previously unknown form of eyeshine resulting from light that enters the eye through the top of the head and optic nerve, eventually emanating through the pupil as a narrow beam: the Optic-Nerve-Transmitted (ONT) eyeshine. We characterize ONT eyeshine in the triplefin blenny Tripterygion delaisi (Tripterygiidae) in comparison to three other teleost species, using behavioural and anatomical observations, spectrophotometry, histology, and magnetic resonance imaging. The study’s aim is to identify the factors that determine ONT eyeshine occurrence and intensity, and whether these are specifically adapted for that purpose. Results: ONT eyeshine intensity benefits from locally reduced head pigmentation, a thin skull, the gap between eyes and forebrain, the potential light-guiding properties of the optic nerve, and, most importantly, a short distance between the head surface and the optic nerves. Conclusions: The generality of these factors and the lack of specifically adapted features implies that ONT eyeshine is widespread among small fish species. Nevertheless, its intensity varies considerably, depending on the specific combination and varying expression of common anatomical features. We discuss whether ONT eyeshine might affect visual performance, and speculate about possible functions such as predator detection, camouflage, and intraspecific communication. Electronic supplementary material The online version of this article (doi:10.1186/s12983-017-0198-9) contains supplementary material, which is available to authorized users

Cdk9 and H2Bub1 signal to Clr6-CII/Rpd3S to suppress aberrant antisense transcription

Mono-ubiquitylation of histone H2B (H2Bub1) and phosphorylation of elongation factor Spt5 by cyclin-dependent kinase 9 (Cdk9) occur during transcription by RNA polymerase II (RNAPII), and are mutually dependent in fission yeast. It remained unclear whether Cdk9 and H2Bub1 cooperate to regulate the expression of individual genes. Here, we show that Cdk9 inhibition or H2Bub1 loss induces intragenic antisense transcription of ∼10% of fission yeast genes, with each perturbation affecting largely distinct subsets; ablation of both pathways de-represses antisense transcription of over half the genome. H2Bub1 and phospho-Spt5 have similar genome-wide distributions; both modifications are enriched, and directly proportional to each other, in coding regions, and decrease abruptly around the cleavage and polyadenylation signal (CPS). Cdk9-dependence of antisense suppression at specific genes correlates with high H2Bub1 occupancy, and with promoter-proximal RNAPII pausing. Genetic interactions link Cdk9, H2Bub1 and the histone deacetylase Clr6-CII, while combined Cdk9 inhibition and H2Bub1 loss impair Clr6-CII recruitment to chromatin and lead to decreased occupancy and increased acetylation of histones within gene coding regions. These results uncover novel interactions between co-transcriptional histone modification pathways, which link regulation of RNAPII transcription elongation to suppression of aberrant initiation

Fate of conjugated natural and synthetic steroid estrogens in crude sewage and activated sludge batch studies

This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Environmental Science & Technology, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/es801952h.Steroids are excreted from the human body in the conjugated form but are present in sewage influent and effluent as the free steroid, the major source of estrogenic activity observed in water courses. The fate of sulfate and glucuronide conjugated steroid estrogens was investigated in batch studies using activated sludge grown on synthetic sewage in a laboratory-scale Husmann simulation and crude sewage from the field. A clear distinction between the fate of sulfate and glucuronide conjugates was observed in both matrices, with sulfated conjugates proving more recalcitrant and glucuronide deconjugation preferential in crude sewage. For each conjugate, the free steroid was observed in the biotic samples. The degree of free steroid formation was dependent on the conjugate moiety, favoring the glucuronide. Subsequent degradation of the free steroid (and sorption to the activated sludge solid phase) was evaluated. Deconjugation followed the first order reaction rate with rate constants for 17α-ethinylestradiol 3-glucuronide, estriol 16α-glucuronide, and estrone 3-glucuronide determined as 0.32, 0.24, and 0.35 h respectively. The activated sludge solid retention time over the range of 3−9 days had 74 to 94% of sulfate conjugates remaining after 8 h. In contrast, a correlation between increasing temperature and decreasing 17α-ethinylestradiol 3-glucuronide concentrations in the activated sludge observed no conjugate present in the AS following 8 h at 22 °C Based on these batch studies and literature excretion profiles, a hypothesis is presented on which steroids and what form (glucuronide, sulfate, or free) will likely enter the sewage treatment plant.EPSR

Primary thermometry in the intermediate Coulomb blockade regime

We investigate Coulomb blockade thermometers (CBT) in an intermediate temperature regime, where measurements with enhanced accuracy are possible due to the increased magnitude of the differential conductance dip. Previous theoretical results show that corrections to the half width and to the depth of the measured conductance dip of a sensor are needed, when leaving the regime of weak Coulomb blockade towards lower temperatures. In the present work, we demonstrate experimentally that the temperature range of a CBT sensor can be extended by employing these corrections without compromising the primary nature or the accuracy of the thermometer.Comment: 8 pages, 4 figure

CATdb: a public access to Arabidopsis transcriptome data from the URGV-CATMA platform

CATdb is a free resource available at http://urgv.evry.inra.fr/CATdb that provides public access to a large collection of transcriptome data for Arabidopsis thaliana produced by a single Complete Arabidopsis Transcriptome Micro Array (CATMA) platform. CATMA probes consist of gene-specific sequence tags (GSTs) of 150–500 bp. The v2 version of CATMA contains 24 576 GST probes representing most of the predicted A. thaliana genes, and 615 probes tiling the chloroplastic and mitochondrial genomes. Data in CATdb are entirely processed with the same standardized protocol, from microarray printing to data analyses. CATdb contains the results of 53 projects including 1724 hybridized samples distributed between 13 different organs, 49 different developmental conditions, 45 mutants and 63 environmental conditions. All the data contained in CATdb can be downloaded from the web site and subsets of data can be sorted out and displayed either by keywords, by experiments, genes or lists of genes up to 100. CATdb gives an easy access to the complete description of experiments with a picture of the experiment design

Comparison of calculation methods used for the determination of anthelmintic resistance in sheep in a temperate continental climate

This study compared results obtained with five different fecal egg count reduction (FECR) calculation methods for defining resistance to ivermectin, fenbendazole, and levamisole in gastrointestinal nematodes of sheep in a temperate continental climate: FECR1 and FECR2 used pre- and posttreatment fecal egg count (FEC) means from both treated and control animals, but FECR1 used arithmetic means, whereas FECR2 used geometric means; FECR3 used arithmetic means for pre- and posttreatment FECs from treated animals only; FECR4 was calculated using only arithmetic means for posttreatment FECs from treated and control animals; and FECR5 was calculated using mean FEC estimates from a general linear mixed model. The classification of farm anthelmintic resistance (AR) status varied, depending on which FECR calculation method was used and whether a bias correction term (BCT, i.e., half the minimum detection limit) was added to the zeroes or not. Overall, agreement between all methods was higher when a BCT was used, particularly when levels of resistance were low. FECR4 showed the highest agreement with all the other FECR methods. We therefore recommend that small ruminant clinicians use the FECR4 formula with a BCT for AR determination, as this would reduce the cost of the FECRT, while still minimizing bias and allowing for comparisons between different farms. For researchers, we recommend the use of FECR1 or FECR2, as the inclusion of both pre- and posttreatment FECs and use of randomly allocated animals in treatment and control groups makes these methods mathematically more likely to estimate the true anthelmintic efficacy