Miracle-dz/UniFAR-FTUs huggingface dataset:
Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors

Objective The aim of this study was to estimate the cost-savings attainable if all patients aged ≥65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health. Setting Primary care setting in Alberta, Canada. Participants Seniors of age 65 years and older currently receiving intramuscular vitamin B12 therapy. Intervention Oral vitamin B12 therapy at 1000 μg/day versus intramuscular therapy at 1000 μg/month. Primary and secondary outcome measures Cost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees. Results Over 5 years, if all Albertans aged 65 years and older who currently receive intramuscular B12 are switched to oral therapy, our model found that $C13 975 883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8 444 346 could be saved from reduced administration costs alone. Conclusions Oral B12 therapy has been shown to be an effective therapeutic option for patients with vitamin B12 deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12 therapy as a clinically and cost-effective first-line therapy for vitamin B12 deficiency.
‘The lesser devil you don’t know’: a qualitative study of smokers’ responses to messages communicating comparative risk of electronic and combusted cigarettes

Introduction Communicating to smokers that e-cigarettes deliver lower levels of harmful chemicals than combusted cigarettes is a challenging issue. This study qualitatively explored smokers’ interpretations of messages communicating the risk of e-cigarettes relative to cigarettes (comparative risk messages). Method We developed 12 print comparative risk messages and evaluated them in 12 focus groups with 72 adult smokers (18+ years old) in Atlanta, Georgia. Results Participants interpreted uncertainty about health effects of e-cigarettes as an indicator of significant unknown risks, which some believed to be potentially more severe than the known effects of cigarettes (such as cancer and heart disease). Also, participants were sceptical about the lower risk claims. Some participants misinterpreted what ‘switching completely’ or ‘switching 100% of the time’ means, perceiving switching from e-cigarettes to combusted cigarettes as comparable with the use of both products. When chemicals in e-cigarettes were mentioned (eg, nicotine or formaldehyde), participants viewed e-cigarettes as very harmful and had difficulty reconciling this belief with the reduced risk claim. Comparative risk messages emphasising smoking risks were perceived as effective. Participants also appreciated being given an option to switch if they cannot quit. Participants suggested the inclusion of more facts and statistics and a credible message source (eg, public health agencies) to increase message effectiveness. Conclusion Comparative risk messages may be more acceptable to smokers if they show direct comparisons of the number of toxic chemicals in cigarettes and e-cigarettes, are attributed to a credible source(s), and emphasise smoking risks.
Coordinating Strategic Capacity Planning in the Semiconductor Industry

We study strategic capacity planning in the semiconductor industry. Working with a major US semiconductor manufacturer on the configuration of their worldwide production facilities, we identify two unique characteristics of this problem as follows: (1) wafer demands and manufacturing capacity are both main sources of uncertainty, and (2) capacity planning must consider the distinct viewpoints from marketing and manufacturing. We formulate a multi-stage stochastic program with demand and capacity uncertainties. To reconcile the marketing and manufacturing perspectives, we consider a decomposition of the planning problem resembling decentralized decision-making. We develop recourse approximation schemes representing different decentralization schemes, which vary in information requirements and complexity. We show that it is possible to arrive at near optimal solutions (within 6.5%) with information decentralization while using a fraction (16.2%) of the computer time.
Optineurin Increases Cell Survival and Translocates to the Nucleus in a Rab8-dependent Manner upon an Apoptotic Stimulus*

In glaucoma the retinal ganglion cells of the retina die through the induction of apoptosis leading to excavation of the optic nerve and blindness. Mutations in the optineurin (optic neuropathy inducing) protein were found associated with an adult form of glaucoma. To date, the role of optineurin in the neurodegeneration process that occurs during glaucoma is still unknown. We now report that in response to an apoptotic stimulus, optineurin changes subcellular localization and translocates from the Golgi to the nucleus. This translocation is dependent on the GTPase activity of Rab8, an interactor of optineurin. Furthermore, we demonstrate that the overexpression of optineurin protects cells from H2O2-induced cell death and blocks cytochrome c release from the mitochondria. A mutated form of optineurin, E50K, identified in normal tension glaucoma patients loses its ability to translocate to the nucleus and when overexpressed compromises the mitochondrial membrane integrity resulting in cells that are less fit to survive under stress conditions. The correlation between optineurin function and cell survival will be key to begin to understand retinal ganglion cell biology and signaling and to design general “survival” strategies to treat a disease of such a complex etiology as glaucoma.
Achieving Learning Outcomes of Acquisition, Fluency, and Application for Adolescents with Difficulty Constructing Simple Sentences.

The present study used a multiple-baseline, single-case experimental design to investigate effects of three sequential experimental conditions on frequency of correct word sequences (CWS) and construction of simple sentences per 1-minute. Sentence Instruction, Frequency Building to a Performance Criteria (FBPC), and Paragraph Instruction comprised the three experimental conditions. Both Instruction conditions ended upon achieving an accuracy criterion of 90%. The FBPC phase lasted at least 5 sessions and ended when participants achieved a fluency criteria of at least 30 CWS with 0 to 3 incorrect word sequences per 1-minute. Participants completed a descriptive paragraph at the end of each experimental condition to measure application of effects to more complicated, compound tasks. Participants included four adolescents with difficulty constructing simple sentences, three females and one male enrolled in grades 810. All participants improved on frequency of sentences per 1-minute. Three of four participants improved CWS per 1-minute. Following instruction and FBPC phases, all participants maintained performance across time and applied higher amounts of CWS and complete simple sentences to descriptive paragraphs. Results extend prior behavioral fluency literature, suggesting acquired, fluent behavior applies to more complicated, compound tasks.
The interleukin-6 –174 G/C promoter polymorphism and arterial stiffness; the Rotterdam Study

Arterial stiffness normally increases with age and has been established as a precursor of cardiovascular disease. Interleukin-6 is a pleiotropic inflammatory cytokine with an important role in the inflammatory cascade, such as up-regulation of C-reactive protein (CRP). The interleukin-6 –174-G/C promoter polymorphism appears to influence levels of inflammatory markers, which have been shown to be associated with arterial stiffness. We studied the association of this polymorphism with levels of interleukin-6 and CRP and with arterial stiffness. The study (n = 3849) was embedded in the Rotterdam Study, a prospective, population-based study. Analyses on the association between the –174-G/C polymorphism and pulse wave velocity, distensibility coefficient, and pulse pressure were performed using analyses of variance. Analyses on the levels of inflammatory markers and arterial stiffness were performed using linear regression analyses. Analyses were adjusted for age, sex, mean arterial pressure, heart rate, known cardiovascular risk factors, and atherosclerosis. We found pulse wave velocity to be 0.35 m/s higher for CC-homozygotes vs. wildtype GG-homozygotes (p = 0.018) with evidence for an allele-dose effect (p trend = 0.013), and a similar pattern for pulse pressure (p trend = 0.041). No apparent consistent association with the distensibility coefficient was found. CRP levels were associated with pulse wave velocity (p = 0.007). In conclusion, the interleukin-6 –174 G/C polymorphism is associated with increased arterial stiffness and pulse pressure.
Comparison of primary afferent and glutamate excitation of neurons in the mammalian spinal dorsal horn

The actions of L-glutamate and agonists, agents blocking their membrane receptors and dorsal root afferent volleys, were compared on intracellularly recorded neuronal activity in an in vitro horizontal slice preparation of the hamster spinal dorsal horn. Bath-applied L- glutamate or L-aspartate (less than or equal to 1 mM) rapidly depolarized and excited less than a third of the dorsal horn neurons sampled. Bathing solutions containing low Ca2+ eliminated synaptic transmission in the slices but failed to block the excitatory effects of L-glutamate for the majority of the neurons tested. N- Acetylaspartylglutamate had no effect on dorsal horn neurons at concentrations up to 1 mM. Neurons excited by L-glutamate were most commonly located in the superficial dorsal horn (laminae I and II). Neurons insensitive to L-glutamate were more broadly distributed, with a number being located in laminae III-V. Kynurenic acid, 2-amino-4- phosphonobutyric acid, and 2,3-piperidine dicarboxylic acid selectively antagonized rapid, short-lasting synaptic components of the dorsal cord potentials. Kynurenic acid reversibly antagonized intracellularly recorded L-glutamate-induced excitation, spontaneous synaptic potentials, and fast synaptic potentials evoked by dorsal root volleys. Compounds with strong antagonist actions at the NMDA receptor, 2-amino- 5-phosphonovaleric acid and D-alpha-aminoadipic acid, were much less effective in suppressing the effects of L-glutamate or in blocking synaptic potentials. We conclude that a subset of spinal neurons directly excited by dorsal root fibers have excitatory membrane receptors activated by L-glutamate. This conclusion is consistent with the concept that L-glutamate or a substance binding to the receptors it activates is released from the central terminals of some primary afferent fibers and mediates fast synaptic transmission from them to certain spinal neurons in the dorsal horn.
Visibly Muslim: Fashion, Politics, Faith

Muslims in Britain and cosmopolitan cities throughout the West are increasingly choosing to express their identity and faith through dress, whether by wearing colourful headscarves, austere black garments or creative new forms of Islamic fashion. Why is dress such an important issue for Muslims? Why is it such a major topic of media interest and international concern? This timely and important book cuts through media stereotypes of Muslim appearances, offering intimate insights into what clothes mean to the people who design and wear them. It examines how different ideas of fashion, politics, faith, freedom, beauty, modesty and cultural diversity are articulated by young British Muslims as they seek out clothes which best express their identities, perspectives and concerns. It also explores the wider social and political effects of their clothing choices on the development of transnational cultural formations and multicultural urban spaces Based on contemporary ethnographic research, the book is an essential read for students and scholars of religion, sociology, cultural studies, anthropology and fashion as well as anyone interested in cultural diversity and the changing face of cosmopolitan cities throughout the world.
Sequential Solution of the Sideways Heat Equation by Windowing of the Data

The sideways heat equation is a one-dimensional model of a problem, where one wants to determine the temperature on the surface of a body using interior measurements. More precisely, we consider a heat conduction problem, where temperature and heat-flux data are available along the line x = 1 and the solution is sought in the interval 0 h x < 1. The problem is ill-posed in the sense that the solution does not depend continuously on the data. Stability can be restored by replacing the time derivative in the heat equation with a bounded spectral approximation. The cut off level in the spectral approximation acts as a regularization parameter, that controls the degree of smoothness in the solution. In certain applications one wants to solve the sideways heat equation in real time, i.e. to constantly update the solution as new measurements are recorded. For this case sequential solution methods are required.
Impact of temperature shifts on the joint evolution of seed dormancy and size

Abstract Seed dormancy and size are two important life‐history traits that interplay as adaptation to varying environmental settings. As evolution of both traits involves correlated selective pressures, it is of interest to comparatively investigate the evolution of the two traits jointly as well as independently. We explore evolutionary trajectories of seed dormancy and size using adaptive dynamics in scenarios of deterministic or stochastic temperature variations. Ecological dynamics usually result in unbalanced population structures, and temperature shifts or fluctuations of high magnitude give rise to more balanced ecological structures. When only seed dormancy evolves, it is counter‐selected and temperature shifts hasten this evolution. Evolution of seed size results in the fixation of a given strategy and evolved seed size decreases when seed dormancy is lowered. When coevolution is allowed, evolutionary variations are reduced while the speed of evolution becomes faster given temperature shifts. Such coevolution scenarios systematically result in reduced seed dormancy and size and similar unbalanced population structures. We discuss how this may be linked to the system stability. Dormancy is counter‐selected because population dynamics lead to stable equilibrium, while small seeds are selected as the outcome of size‐number trade‐offs. Our results suggest that unlike random temperature variation between generations, temperature shifts with high magnitude can considerably alter population structures and accelerate life‐history evolution. This study increases our understanding of plant evolution and persistence in the context of climate changes.
Three-dimensional localization of T-cell receptors in relation to microvilli using a combination of superresolution microscopies

Significance T lymphocytes play a central role in cell-mediated immunity. Their surfaces are covered by narrow and short protrusions called microvilli. It is not known whether there is a role for microvilli in the immune response. To shed light on this question, we probed the location of T-cell receptors (TCRs), the molecules that initiate the immune response of T cells, with respect to the 3D structure of microvilli. Superresolution optical microscopy showed that TCRs are highly concentrated on microvilli. Previous studies stressed the role of small clusters of TCRs in the immune process; our study provides a natural explanation as to how these clusters form. Leukocyte microvilli are flexible projections enriched with adhesion molecules. The role of these cellular projections in the ability of T cells to probe antigen-presenting cells has been elusive. In this study, we probe the spatial relation of microvilli and T-cell receptors (TCRs), the major molecules responsible for antigen recognition on the T-cell membrane. To this end, an effective and robust methodology for mapping membrane protein distribution in relation to the 3D surface structure of cells is introduced, based on two complementary superresolution microscopies. Strikingly, TCRs are found to be highly localized on microvilli, in both peripheral blood human T cells and differentiated effector T cells, and are barely found on the cell body. This is a decisive demonstration that different types of T cells universally localize their TCRs to microvilli, immediately pointing to these surface projections as effective sensors for antigenic moieties. This finding also suggests how previously reported membrane clusters might form, with microvilli serving as anchors for specific T-cell surface molecules.
5‐fluorouracil‐related gene expression levels in primary colorectal cancer and corresponding liver metastasis

Gene expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) have been shown to be associated with response to 5‐fluorouracil‐based therapies. Analyzing these gene expression levels in liver metastases is important to obtain the best prediction of therapy. Our aim was to determine how TS, DPD, TP and OPRT gene expression levels in primary colorectal cancer (CRC) were related to those in liver metastases. Formalin‐fixed, paraffin‐embedded tumor specimens from 31 pairs of primary CRC and corresponding liver metastases were dissected by using laser‐captured microdissection. RNA was extracted and cDNA was prepared by reverse‐transcription. Quantitation of target gene and internal reference gene was performed using real‐time PCR. No significant difference was seen between median mRNA expression levels of TS, DPD, TP and OPRT in primary cancer and those in corresponding liver metastases (median value: TS 1.48 vs. 1.43; p = 0.92, DPD 0.19 vs.0.12; p = 0.10, TP 1.20 vs. 0.98; p = 0.39, OPRT 1.17 vs. 0.95; p = 0.10). When matched tissue sets were compared on an individual basis, there was a significant correlation for TS mRNA expression between primary cancer and corresponding liver metastases (rs = 0.52, p = 0.0026). However, no correlation was seen between matched sets for DPD, TP or OPRT. Significant correlation was seen between DPD and TP expression levels in both primary CRC (rs = 0.38, p = 0.03) and liver metastases (rs = 0.72, p < 0.0001). A good prediction of TS mRNA levels in liver metastases can be obtained by measuring those of primary CRC, although no correlation was seen for DPD, TP and OPRT. © 2006 Wiley‐Liss, Inc.
A Local Detection Approach for Named Entity Recognition and Mention Detection

In this paper, we study a novel approach for named entity recognition (NER) and mention detection (MD) in natural language processing. Instead of treating NER as a sequence labeling problem, we propose a new local detection approach, which relies on the recent fixed-size ordinally forgetting encoding (FOFE) method to fully encode each sentence fragment and its left/right contexts into a fixed-size representation. Subsequently, a simple feedforward neural network (FFNN) is learned to either reject or predict entity label for each individual text fragment. The proposed method has been evaluated in several popular NER and MD tasks, including CoNLL 2003 NER task and TAC-KBP2015 and TAC-KBP2016 Tri-lingual Entity Discovery and Linking (EDL) tasks. Our method has yielded pretty strong performance in all of these examined tasks. This local detection approach has shown many advantages over the traditional sequence labeling methods.
Modeling the Effect of the Spatial Pattern of Airborne Lidar Returns on the Prediction and the Uncertainty of Timber Merchantable Volume

Lidar data are regularly used to characterize forest structures. In this study, we determine the effects of three lidar attributes (density, spacing, scanning angle) on the accuracy and the uncertainty of timber merchantable volume estimates of balsam fir stands (Abies balsamea (L.) Mill. ) in eastern Canada. We used lidar point clouds to compute predictor variables of the merchantable volume in a nonlinear model. The best model included the mean height of first returns, the proportion of first returns below 2 m and the canopy surface roughness index. Our analysis shows a high correlation between lidar and field data of 119 plots (pseudo-R2 = 0.91), however, residuals were heteroscedastic. More precise parameter estimates were obtained by adding to the model a variance function of variables describing the mean height of returns and the skewness of the area distribution of triangulated lidar returns. The residual standard deviation was better estimated (3.7 m3 ha−1 multiplied by the variance function versus 28.0 m3 ha−1). We found no effect of density on the predictions (p-value = 0.74). This suggests that the height and the spatial pattern of returns, rather than the density, should be considered to better assess the uncertainty of merchantable volume estimates.
Feature Weighted Support Vector Machines for Writer-Independent On-Line Signature Verification

In this paper we present a novel framework for writer-independent on-line signature verification. This framework utilises a dynamic time warping-based dichotomy transformation and a writer-specific dissimilarity normalisation technique, in order to obtain a robust writer-independent signature representation in dissimilarity space. Support vector machines are utilised for signature modelling and verification. Linear and radial basis function kernels are investigated. In the case of the radial basis function kernel, both conventional and feature weighted variants are considered. We show that the non-linear kernel significantly outperforms its linear counterpart. We also show that the incorporation of feature weights into the non-linear kernel function consistently improves verification proficiency. When evaluated on the Philips signature database, which contains 1530 genuine signatures and 3000 amateur skilled forgeries from 51 writers, we show that equal error rates of 1.26% and 3.52% are expected when 15 and 5 genuine reference samples are considered per writer. This performance estimate compares favourably with those of existing systems also evaluated on this data set. Furthermore, there is sufficient evidence to suggest that further investigation into the feature set considered, as well as the feature weighting strategy utilised, may further improve performance.