Quality safeguards and regulation of online pharmacies

Using econometric evidence, this article confirms that distribution ofmedicines online is split into two market segments of very diversequality, and identifies the factors that drive quality and qualityassurance in this activity. Unlike fraudulent, rogue, websites, whichoffer scant guarantees and usually sell just a few medicines withoutprescription, online pharmacies offering insurance coverage and linkedto conventional pharmacies typically sell a wholerange of drugs, require third-party medical prescriptions and provideabundant information to patients. It is shown that, where onlinepharmacies are allowed to act legally, market forces enhance quality,as private insurers require professional standards, and specialized thirdparties make a business of certifying them. Furthermore, older onlinepharmacies and those running conventional operations offer higherquality, probably because of reputational investments. Overall, this evidence supports licensing online pharmacies, especiallyconsidering that prohibiting them is ineffective against fraudulent sites.

Sense and antisense transcripts in the histone H1 (HIS-1) locus of Leishmania major.

Histone H1 in the parasitic protozoan Leishmania is a developmentally regulated protein encoded by two genes, HIS-1.1 and HIS-1.2. These genes are separated by approximately 20 kb of sequence and are located on the same DNA strand of chromosome 27. When Northern blots of parasite RNA were probed with HIS-1 strand-specific riboprobes, we detected sense and antisense transcripts that were polyadenylated and developmentally regulated. When the HIS-1.2 coding region was replaced with the coding region of the neomycin phosphotransferase gene, antisense transcription of this gene was unaffected, indicating that the regulatory elements controlling antisense transcription were located outside of the HIS-1.2 gene, and that transcription in Leishmania can occur from both DNA strands even in the presence of transcription of a selectable marker in the complementary strand. A search for other antisense transcripts within the HIS-1 locus identified an additional transcript (SC-1) within the intervening HIS-1 sequence, downstream of adenine and thymine-rich sequences. These results show that gene expression in Leishmania is not only regulated polycistronically from the sense strand of genomic DNA, but that the complementary strand of DNA also contains sequences that could drive expression of open reading frames from the antisense strand of DNA. These findings suggest that the parasite has evolved in such a way as to maximise the transcription of its genome, a mechanism that might be important for it to maintain virulence.

On the drivers of commodity co-movement: Evidence from biofuels

We use the recent introduction of biofuels to study the effect of industry factors on the relationshipsbetween wholesale commodity prices. Correlations between agricultural products and oilare strongest in the 2005-09 period, coinciding with the boom of biofuels, and remain substantialuntil 2011. We disentangle three possible drivers for the linkage: substitution, energy costs, andfinancialization. The timing and magnitude of the biofuels-to-oil relationships are different to thoseof other commodities, and far higher than can be justified by costs and financialization. Substitutionand costs drive the monthly correlations of long-term futures, and each of the three contributeequally to the daily co-movement of the short-term ones. The findings survive many robustnesschecks and appear in the stock market.

Molecular determinants of vesicular storage and release of the gliotransmitter D-serine from cortical astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of 'gliotransmitters' such as glutamate, ATP or D-serine. A calcium-dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. Over the last years, we have been studying the molecular determinants governing D-serine release from glia using different approaches. Using a novel bioassay for D-serine, we have been able to show that D-serine release occurs mainly through a calcium- and SNARE proteindependent mechanism just supporting the idea that this amino acid is released by exocytosis from glia. We next have pursued our exploration by confocal imaging and tracking of the exocytotic routes for Dserine- mediated gliotransmission and have shown that D-serine releasable pools are confined to synaptobrevin2/cellubrevin-bearing vesicles. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2- positive vesicles from rat cortical astrocytes in culture while preserving their content in gliotransmitters. The purified organelles are clear round shape vesicles of excellent purity with homogeneous size (40 nm) as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles like synaptic vesicle protein 2 (SV2) and the proton pump H?-ATPase. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electrophoresis coupled to laser-induced fluorescence detection. The purified vesicles contain large amount of D-serine. We also detect peaks corresponding to unidentified compounds that may correspond to others amino acids. Postembedding immunogold labelling of the rat neocortex further revealed the expression of D-serine in astrocytes processes contacting excitatory synapses. Finally, we have examined the uptake properties for Dserine and glutamate inside the isolated glial vesicles. Our results provide significant support for the existence of an uptake system for D-serine in secretory glial vesicles and for the storage of chemical substances like D-serine and glutamate. 11th International Congress on Amino Acids, Peptides and Proteins 763 123

General trends in world biogeographic literature: a preliminary bibliometric analysis

Records with the search string biogeograph* were collected from the Science Citation Index (SCI). A total of 3456 records were downloaded for the 1945-2006 period from titles of articles and reviews, and 10,543 records were downloaded for 1991-2006, taking into consideration also abstracts and keywords. Temporal trends of publications, geographical and institutional distribution of the research output, authorship, and core journals were evaluated. There were as many as 122 countries carrying out biogeographic research; in the most recent period, USA is the top producing country, followed by the United Kingdom, Australia, France, Germany, Spain, and Canada. There were 17,493 authors contributing to the field. During 1991-2006 there were 4098 organizations with authors involved in biogeographic research; institutions with higher number of papers are the Natural History Museum (United Kingdom), the University of California, Berkeley (USA), the Museum National d'Histoire Naturelle (France), the Universidad Nacional Autónoma de México (Mexico), the American Museum of Natural History (USA) and the Russian Academy of Sciences (Russia). Research articles are spread over a variety of journals, with the Journal of Biogeography, Molecular Phylogenetics and Evolution, Molecular Ecology, and Biological Journal of the Linnean Society being the core journals. From 28,759 keywords retrieved those with the highest frequency were evolution, phylogeny, diversity, mitochondrial DNA, pattern(s), systematics, and population(s). We conclude that publications on biogeography have increased substantially during the last years, especially since 1998. The preferred journal for biogeographic papers is the Journal of Biogeography. Most frequent keywords seem to indicate that biogeography fits well within both evolutionary biology and ecology, with molecular biology and phylogenetics being important factors that drive their current development.

Drug innovation, prices and health

This article tries to reconcile economic-industrial policy with health policy when dealing with biomedical innovation and welfare state sustainability. Better health accounts for an increasingly large proportion of welfare improvements. Explanation is given to the welfare losses coming from the fact than industrial and health policy tend to ignore each other. Drug s prices reflecting their relative relative effectiveness send the right signal to the industry rewarding innovation with impact on quantity and quality of life- and to the buyers of health care services.The level of drug s public reimbursement indicates the social willingness to pay of the different national health systems, not only by means of inclusion, or rejection, in the basket of services covered, but especially establishing the proportion of the price that is going to be financed publicly.Reference pricing for therapeutic equivalents as the upper limit of the social willingness to pay- and two-tiered co-payments for users (avoidable and inversely related with the incremental effectiveness of de drug) are deemed appropriate for those countries concerned at the same time with increasing their productivity and maintaining its welfare state. Profits drive R&D but not its location. There is no intrinsic contradiction between high productivity and a consolidated National Health Service (welfare state) as the European Nordic Countries are telling us every day.

Respiration, metabolic balance, and attention in affective picture processing

The jointly voluntary and involuntary control of respiration, unique among essential physiological processes, the interconnection of breathing with and its influence on the autonomic nervous system, and disease states associated with the interface between psychology and respiration (e.g., anxiety disorders, hyperventilation syndrome, asthma) make the study of the relationship between respiration and emotion both theoretically and clinically of great relevance. However, the respiratory behavior during affective states is not yet completely understood. We studied breathing pattern responses to 13 picture series varying widely in their affective tone in 37 adults (18 men, 19 women, mean age 26). Time and volume parameters were recorded with the LifeShirt system (VivoMetrics Inc., Ventura, California, USA, see image). We also measured end-tidal pCO2 (EtCO2) with a Microcap Handheld Capnograph (Oridion Medical 1987 Ltd., Jerusalem, Israel) to determine if ventilation is in balance with metabolic demands and spontaneous eye-blinking to investigate the link between respiration and attention. At the end of each picture series, the participants reported their subjective feeling in the affective dimensions of pleasantness and arousal. Increasing self-rated arousal was associated with increasing minute ventilation but not with decreases in EtCO2, suggesting that ventilatory changes during picture viewing paralleled variations in metabolic activity. EtCO2 correlated with pleasantness, and eye-blink rate decreased with increasing unpleasantness in line with a negativity bias in attention. Like MV, inspiratory drive (i.e., mean inspiratory flow) increased with arousal. This relationship reflected increases in inspiratory volume rather than shortening of the time parameters. This study confirms that respiratory responses to affective stimuli are organized to a certain degree along the dimensions of pleasantness and arousal. It shows, for the first time, that during picture viewing, ventilatory increases with increasing arousal are in balance with metabolic activity and that inspiratory volume is modulated by arousal. MV emerges as the most reliable respiratory index of self-perceived arousal. Finally, end-tidal pCO2 is slightly lower during processing of negative as compared to positive picture contents, which is proposed to enhance sensory perception and reflect a negativity bias in attention.

First nationwide study on driving under the influence of drugs in Switzerland.

In Switzerland, a two-tier system based on impairment by any psychoactive substances which affect the capacity to drive safely and zero tolerance for certain illicit drugs came into force on 1 January 2005. According to the new legislation, the offender is sanctioned if Delta(9)-tetrahydrocannabinol THC is >or=1.5ng/ml or amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), cocaine, free morphine are >or=15ng/ml in whole blood (confidence interval+/-30%). For all other psychoactive substances, impairment must be proven in applying the so-called "three pillars expertise". At the same time the legal blood alcohol concentration (BAC) limit for driving was lowered from 0.80 to 0.50g/kg. The purpose of this study was to analyze the prevalence of drugs in the first year after the introduction of the revision of the Swiss Traffic Law in the population of drivers suspected of driving under the influence of drugs (DUID). A database was developed to collect the data from all DUID cases submitted by the police or the Justice to the eight Swiss authorized laboratories between January and December 2005. Data collected were anonymous and included the age, gender, date and time of the event, the type of vehicle, the circumstances, the sampling time and the results of all the performed toxicological analyses. The focus was explicitly on DUID; cases of drivers who were suspected to be under the influence of ethanol only were not considered. The final study population included 4794 DUID offenders (4243 males, 543 females). The mean age of all drivers was 31+/-12 years (range 14-92 years). One or more psychoactive drugs were detected in 89% of all analyzed blood samples. In 11% (N=530) of the samples, neither alcohol nor drugs were present. The most frequently encountered drugs in whole blood were cannabinoids (48% of total number of cases), ethanol (35%), cocaine (25%), opiates (10%), amphetamines (7%), benzodiazepines (6%) and methadone (5%). Other medicinal drugs such as antidepressants and benzodiazepine-like were detected less frequently. Poly-drug use was prevalent but it may be underestimated because the laboratories do not always analyze all drugs in a blood sample. This first Swiss study points out that DUID is a serious problem on the roads in Switzerland. Further investigations will show if this situation has changed in the following years.

Scale-dependent adaptive evolution and morphological convergence to climatic niche in Californian eriogonoids (Polygonaceae)

Aim Macroevolutionary patterns and processes change substantially depending on levels of taxonomic and ecological organization, and the resolution of environmental and spatial variability. In comparative methods, the resolution of environmental and spatial variability often defines the number of selective regimes used to test whether phenotypic characteristics are adaptively correlated with the environment. Here, we examine how investigator choice of the number of selective regimes, determined by varying the resolution of among-species variability in the species climatic niche (hereafter called ecological scale'), influences trait morphological diversification among Eriogonoideae species. We assess whether adaptive or neutral processes drive the evolution of several morphological traits in these species. Location South-western North America. Methods We applied a phylogenetic framework of three evolutionary models to four morphological traits and the climatic niches of Eriogonoideae (in the buckwheat family, Polygonaceae). We tested whether morphological traits evolve in relation to climate by adaptive or neutral process, and whether the resulting patterns of morphological variability are conserved or convergent across the clade. We inspected adaptive models of evolution under different levels of resolution of among-species variability of the climatic niche. Results We show that morphological traits and climate niches of Eriogonoideae species are not phylogenetically conserved. Further, adaptive evolution of phenotypic traits is specific to climatic niche occupancy across this clade. Finally, the likely evolutionary process and the level of detectable niche conservatism change depending on the resolution of environmental variability of the climatic niche. Main conclusions Our study demonstrates the need to consider both the resolution of environmental variability and alternative evolutionary models to understand the morphological diversification that accompanies divergent adaptive evolution of lineages to climatic conditions.

Influence of learning on range expansion and adaptation to novel habitats.

Learning has been postulated to 'drive' evolution, but its influence on adaptive evolution in heterogeneous environments has not been formally examined. We used a spatially explicit individual-based model to study the effect of learning on the expansion and adaptation of a species to a novel habitat. Fitness was mediated by a behavioural trait (resource preference), which in turn was determined by both the genotype and learning. Our findings indicate that learning substantially increases the range of parameters under which the species expands and adapts to the novel habitat, particularly if the two habitats are separated by a sharp ecotone (rather than a gradient). However, for a broad range of parameters, learning reduces the degree of genetically-based local adaptation following the expansion and facilitates maintenance of genetic variation within local populations. Thus, in heterogeneous environments learning may facilitate evolutionary range expansions and maintenance of the potential of local populations to respond to subsequent environmental changes.

Temporal Geobiotic Mapping: a conceptual mapping technique toward visualising geobiotic areas in cross-section

Geobiota are defined by taxic assemblages (i.e., biota) and their defining abiotic breaks, which are mapped in cross-section to reveal past and future biotic boundaries. We term this conceptual approach Temporal Geobiotic Mapping (TGM) and offer it as a conceptual approach for biogeography. TGM is based on geological cross-sectioning, which creates maps based on the distribution of biota and known abiotic factors that drive their distribution, such as climate, topography, soil chemistry and underlying geology. However, the availability of abiotic data is limited for many areas. Unlike other approaches, TGM can be used when there is minimal data available. In order to demonstrate TGM, we use the well-known area in the Blue Mountains, New South Wales (NSW), south-eastern Australia and show how surface processes such as weathering and erosion affect the future distribution of a Moist Basalt Forest taxic assemblage. Biotic areas are best represented visually as maps, which can show transgressions and regressions of biota and abiota over time. Using such maps, a biogeographer can directly compare animal and plant distributions with features in the abiotic environment and may identify significant geographical barriers or pathways that explain biotic distributions.

The three strands of intercultural polities: a comprehensive view. A critical review of Bouchard and Cantle recent books on interculturalism

Within the emerging policy debate on interculturalism we critically review two recent books in 2012: Bouchard’s L’interculturalisme: un point de vue quebecois, and Cantle’s Interculturalism: The New Era of Cohesion and Diversity. In my view, both contribute very directly to open a foundational debate on interculturalism. In addressing the point of convergence and the dividing lines of these two contributions, I will claim that in spite of having one core concept of interculturalism, there are, however, at least two basic conceptions that have to be interpreted in complementary ways: Bouchard’s essay represents the contractual strand, Cantle’s book the cohesion strand. At the end I would also suggest that these two strands do not manage to express explicitly that diversity can also be seen as a resource of innovation and creativity, and so can drive individual and social development. This view is based on the diversity advantage literature already informing most of the diversity debate in Europe and elsewhere. This is what I will call the constructivist strand. My ultimate purpose is to defend a comprehensive view, grounded on the argument that no one can have the sole authority to define intercultural policy, since the three strands can be applied at different moments, according to different purposes and policy needs. The challenge now is that policy managers be able to achieve a balance between these three policy drivers.

Speed Limit Questions? Here’s Your Answer, July 6, 2005

Iowa’s speed regulations are based on the same basic speed law that is used in all 50 states: “Any person driving a motor vehicle on a highway shall drive the same at a careful and prudent speed not greater than nor less than is reasonable and proper, having due regard to the traffic, surface, and width of the highway and of any other conditions then existing, and no person shall drive any vehicle upon a highway at a speed greater than will permit the person to bring it to a stop within the assured clear distance ahead, such driver having the right to assume, however, that all persons using said highway will observe the law.” Statutory limits are based on the concept that uniform categories of highways can be traveled safely at certain preset maximum speeds under ideal conditions. Whether the speed limit is posted or unposted, drivers should reduce their speed below these values in poor weather, heavy traffic, and under other potentially hazardous conditions.

You’re the COACH!: A Guide for Parents of New Drivers, June 23, 2008

This publication is a guide for parents and guardians of teenagers learning to drive. It should be used with the Iowa Driver’s Manual to aid you in instructing your new driver about how to safely and responsibly operate a motor vehicle. Since the task of driving is affected by changing conditions, this manual does not attempt to cover all situations that may arise. Under Iowa’s graduated driver licensing system young drivers must complete 20 hours of supervised drive time with their parents or guardians during the instruction permit stage and 10 hours during the intermediate license stage. Even though your teenager is taking or has completed driver education in school, there is a great deal of benefit to be obtained from you providing this additional practice time. Learning from your experience and under your guidance, your teenager will apply the rules of the road and more fully understand the risks involved in driving. This will require time and patience on your part, but the effort will result in you knowing that your teenager will be better able to cope with the demands of safe driving. In the back of this manual you will find several pages of diagrams. Use these diagrams to illustrate different driving situations for your teenage driver. Consider taking a notepad and pencil along during your practice sessions for additional drawings. This manual also contains a chart to log your supervised drive time. As your new driver advances through the graduated system you will be required to certify to an Iowa driver’s license examiner that you completed the minimum number of hours of supervised drive time. By becoming involved in the learning driver’s educational process, you are contributing to Iowa’s overall highway safety effort and helping your teenager develop safe driving habits that will last a lifetime.

Evaluation of an online, case-based interactive approach to teaching pathophysiology

Rapport de synthèse : L'article qui fait l'objet de ma thèse évalue une nouvelle approche pédagogique pour l'apprentissage de certains chapitres de physiopathologie. Le dispositif pédagogique se base sur l'alternance d'apprentissage ex-cathedra et de l'utilisation d'un site web comprenant des vignettes cliniques. Lors de la consultation de ces-dernières, l'étudiant est invité à demander des examens de laboratoire dont il pourrait justifier la pertinence selon le cas clinique étudié. La nouveauté du procédé réside dans le fait que, préalablement à son cours ex-cathedra, l'enseignant peut consulter les statistiques de demandes de laboratoire et ainsi orienter son cours selon les éléments mal compris par les étudiants. A la suite du cours ex-cathedra, les étudiants peuvent consulter sur internet la vignette clinique complète avec des explications. A l'issue de tout le cours, une évaluation auprès des étudiants a été conduite. Le procédé a été mis en place durant deux années consécutives et l'article en discute notamment les résultats. Nous avons pu conclure que cette méthode innovatrice d'enseignement amène les étudiants à mieux se préparer pour les cours ex-cathedra tout en permettant à l'enseignant d'identifier plus précisément quelles thématiques étaient difficiles pour les étudiants et donc d'ajuster au mieux son cours. Mon travail de thèse a consisté à créer ce dispositif d'apprentissage, à créer l'application web des vignettes cliniques et à l'implanter durant deux années consécutives. J'ai ensuite analysé les données des évaluations et écrit l'article que j'ai présenté à la revue 'Medical Teacher'. Après quelques corrections et précisions demandées par le comité de lecture, l'article a été accepté et publié. Ce travail a débouché sur une seconde version de l'application web qui est actuellement utilisée lors du module 3.1 de 3è année à l'Ecole de Médecine à Lausanne. Summary : Since the early days of sexual selection, our understanding of the selective forces acting on males and females during reproduction has increased remarkably. However, despite a long tradition of experimental and theoretical work in this field and relentless effort, numerous questions remain unanswered and many results are conflicting. Moreover, the interface between sexual selection and conservation biology has to date received little attention, despite existing evidence for its importance. In the present thesis, I first used an empirical approach to test various sexual selection hypotheses in a population of whitefish of central Switzerland. This precise population is characterized by a high prevalence of gonadal alterations in males. In particular, I challenged the hypothesis that whitefish males displaying peculiar gonadal features are of lower genetic quality than other seemingly normal males. Additionally, I also worked on identifying important determinant of sperm behavior. During a second theoretical part of my work, which is part of a larger project on the evolution of female mate preferences in harvested fish populations, I developed an individual-based simulation model to estimate how different mate discrimination costs affect the demographical behavior of fish populations and the evolutionary trajectories of female mate preferences. This latter work provided me with some insight on a recently published article addressing the importance of sexual selection for harvesting-induced evolution. I built upon this insight in a short perspective paper. In parallel, I let some methodological questions drive my thoughts, and wrote an essay about possible synergies between the biological, the philosophical and the statistical approach to biological questions.