Neue Entwicklungen in der Pharmakotherapie der Kokainabhängigkeit

Zusammenfassung: Es zeichnen sich neue medikamentöse Behandlungsmöglichkeiten der Kokainabhängigkeit ab. So gelang es erstmals mit Disulfiram in einer randomisierten, kontrollierten Studie, den Kokainkonsum signifikant zu reduzieren. Im Oktober2003 startete in den USA eine Phase-IIb-Studie mit aktiver Immunisierung gegen Kokain, seit September2004 läuft in der Schweiz eine Behandlungsstudie mit Methylphenidat in Kombination mit kognitiver Verhaltenstherapie. Vigabatrin, Tiagabin, Selegilin und Topiramat haben sich in Pilotuntersuchungen als potenzielle Kandidatensubstanzen für die weitere klinische Prüfung empfohle

A Valuation Analysis of the Physical Oceanographic Real Time System (PORTS)

This analysis estimates several economic benefits derived from national implementation of the National Oceanic and Atmospheric Administration’s Physical Oceanographic Real-Time System (PORTS®) at the 175 largest ports in the United States. Significant benefits were observed owing to: (1) lower commercial marine accident rates and resultant reductions in morbidity, mortality and property damage; (2) reduced pollution remediation costs; and, (3) increased productivity associated with operation of more fully loaded commercial vessels. Evidence also suggested additional benefits from heightened commercial and recreational fish catch and diminished recreational boating accidents. Annual gross benefits from 58 current PORTS® locations exceeded $217 million with an addition$83 million possible if installed at the largest remaining 117 ports in the United States. Over the ten-year economic life of PORTS® instruments, the present value for installation at all 175 ports could approach $2.5 billion

Gathering in the City: An Annotated Bibliography and Review of the Literature About Human-Plant Interactions in Urban Ecosystems

The past decade has seen resurgence in interest in gathering wild plants and fungi in cities. In addition to gathering by individuals, dozens of groups have emerged in U.S., Canadian, and European cities to facilitate access to nontimber forest products (NTFPs), particularly fruits and nuts, in public and private spaces. Recent efforts within cities to encourage public orchards and food forests, and to incorporate more fruit and nut trees into street tree planting programs indicate a growing recognition among planners that gathering is an important urban activity. Yet the academic literature has little to say about urban gathering practices or the people who engage in them. This annotated bibliography and literature review is a step toward filling the gap in knowledge about the socioecological roles of NTFPs in urban ecosystems in the United States. Our objectives are to demonstrate that gathering—the collecting of food and raw materials—is a type of human-plant interaction that warrants greater attention in urban green space management, and to provide an overview of the literature on human-plant interactions—including gathering—in urban environments. Our review found that very few studies of urban gathering have been done. Consequently, we included gathering field guides, Web sites, and articles from the popular media in our search. These sources, together with the small number of scientific studies of urban gathering, indicated that people derive numerous benefits from gathering plants and fungi in U.S. cities. Gathering provides useful products, encourages physical activity, offers opportunities to connect with and learn about nature, helps strengthen social ties and cultural identities, and, in some contexts, can serve as a strategic tool for ecological restoration. These benefits parallel those identified in environmental psychology and cultural ecology studies of the effects of gardening and being in nature. The literature on human-plant interactions also emphasizes that humans need to be treated as endogenous factors in dynamic, socially and spatially heterogeneous urban ecosystems. Spatially explicit analyses of human-plant interactions show that the distribution of wealth and power within societies affects the composition, species distribution, and structure of urban ecologies. Our review also indicates that tensions exist between NTFP gatherers and land managers, as well as between gatherers and other citizens over gathering, particularly in public spaces. This tension likely is related to perceptions about the impact these practices have on cherished species and spaces. We conclude that gathering is an important urban activity and deserves a greater role in urban management given its social and potential ecological benefits. Research on urban gathering will require sensitivity to existing power imbalances and the use of theoretical frameworks and methodologies that assume humans are integral and not always negative components of ecosystems

Variational Monte Carlo study of the ground state properties and vacancy formation energy of solid para-H2 using a shadow wave function

A Shadow Wave Function (SWF) is employed along with Variational Monte Carlo techniques to describe the ground state properties of solid molecular para-hydrogen. The study has been extended to densities below the equilibrium value, to obtain a parameterization of the SWF useful for the description of inhomogeneous phases. We also present an estimate of the vacancy formation energy as a function of the density, and discuss the importance of relaxation effects near the vacant site

Long-lived neutral-kaon flux measurement for the KOTO experiment

The KOTO ($K^0$ at Tokai) experiment aims to observe the CP-violating rare decay $K_L \rightarrow \pi^0 \nu \bar{\nu}$ by using a long-lived neutral-kaon beam produced by the 30 GeV proton beam at the Japan Proton Accelerator Research Complex. The $K_L$ flux is an essential parameter for the measurement of the branching fraction. Three $K_L$ neutral decay modes, $K_L \rightarrow 3\pi^0$, $K_L \rightarrow 2\pi^0$, and $K_L \rightarrow 2\gamma$ were used to measure the $K_L$ flux in the beam line in the 2013 KOTO engineering run. A Monte Carlo simulation was used to estimate the detector acceptance for these decays. Agreement was found between the simulation model and the experimental data, and the remaining systematic uncertainty was estimated at the 1.4\% level. The $K_L$ flux was measured as $(4.183 \pm 0.017_{\mathrm{stat.}} \pm 0.059_{\mathrm{sys.}}) \times 10^7$ $K_L$ per $2\times 10^{14}$ protons on a 66-mm-long Au target.Comment: 27 pages, 16 figures. To be appeared in Progress of Theoretical and Experimental Physic

A Monte Carlo study of the three-dimensional Coulomb frustrated Ising ferromagnet

We have investigated by Monte-Carlo simulation the phase diagram of a three-dimensional Ising model with nearest-neighbor ferromagnetic interactions and small, but long-range (Coulombic) antiferromagnetic interactions. We have developed an efficient cluster algorithm and used different lattice sizes and geometries, which allows us to obtain the main characteristics of the temperature-frustration phase diagram. Our finite-size scaling analysis confirms that the melting of the lamellar phases into the paramgnetic phase is driven first-order by the fluctuations. Transitions between ordered phases with different modulation patterns is observed in some regions of the diagram, in agreement with a recent mean-field analysis.Comment: 14 pages, 10 figures, submitted to Phys. Rev.

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

<p>Abstract</p> <p>Background</p> <p>Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies.</p> <p>Methods</p> <p>Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients.</p> <p>Results</p> <p>We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). <it>CYP3A4*1B</it>, <it>CYP3A5*3 </it>and <it>CYP3A5*6 </it>alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. <it>CYP3A5*1/CYP3A5*1 </it>and <it>CYP3A5*1/CYP3A5*3 </it>genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin.</p> <p>Conclusion</p> <p>A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.</p

Traditional Taxonomic Groupings Mask Evolutionary History: A Molecular Phylogeny and New Classification of the Chromodorid Nudibranchs

Chromodorid nudibranchs (16 genera, 300+ species) are beautiful, brightly colored sea slugs found primarily in tropical coral reef habitats and subtropical coastal waters. The chromodorids are the most speciose family of opisthobranchs and one of the most diverse heterobranch clades. Chromodorids have the potential to be a model group with which to study diversification, color pattern evolution, are important source organisms in natural products chemistry and represent a stunning and widely compelling example of marine biodiversity. Here, we present the most complete molecular phylogeny of the chromodorid nudibranchs to date, with a broad sample of 244 specimens (142 new), representing 157 (106 new) chromodorid species, four actinocylcid species and four additional dorid species utilizing two mitochondrial markers (16s and COI). We confirmed the monophyly of the Chromodorididae and its sister group relationship with the Actinocyclidae. We were also able to, for the first time, test generic monophyly by including more than one member of all 14 of the non-monotypic chromodorid genera. Every one of these 14 traditional chromodorid genera are either non-monophyletic, or render another genus paraphyletic. Additionally, both the monotypic genera Verconia and Diversidoris are nested within clades. Based on data shown here, there are three individual species and five clades limited to the eastern Pacific and Atlantic Oceans (or just one of these ocean regions), while the majority of chromodorid clades and species are strictly Indo-Pacific in distribution. We present a new classification of the chromodorid nudibranchs. We use molecular data to untangle evolutionary relationships and retain a historical connection to traditional systematics by using generic names attached to type species as clade names

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments