58 resultados para Over-Enforcement of Patents


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1. The acceptance of reserves as a useful management strategy relies on evidence of their effectiveness in preserving stocks of harvested species and conserving biodiversity. A history of ad hoc decisions in terrestrial and marine protected area planning has meant that many of these areas are contributing inefficiently to conservation goals. The conservation value of existing protected areas should be assessed when planning the placement of additional areas in a reserve network. 2. This study tested (1) the effectiveness of protection for intertidal molluscs of a marine reserve (Bouddi Marine Extension, NSW, Australia) established in 1971, and (2) the contribution of the protected area to the conservation of regional species, assemblages, and habitats. 3. The shell length and population density of one harvested (Cellana tramoserica), and three non-harvested species (Bembicium nanum, Morula marginalba, Nerita atramentosa) of intertidal molluscs were examined in the protected area and two reference locations over two seasons. 4. The heavily collected limpet C. tramoserica was significantly larger in the protected area and was the only species to exhibit a significant difference. No species significantly differed in population density between the protected area and reference locations. 5. Temporally replicated surveys of macro-molluscs at 21 locations over 75km of coastline identified that the existing protected area included 50% of species, two of five assemblage types and 19 of 20 intertidal rocky shore habitats surveyed in the study region. Reservation of a further three rocky reefs would protect a large proportion of species (71%), a representative of each assemblage and all habitat types. 6. Despite originally being selected in the absence of information on regional biodiversity, the protected area is today an effective starting point for expansion to a regional network of intertidal protected areas.

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Background: Recently, Cipriani and colleagues examined the relative efficacy of 12 new-generation antidepressants on major depression using network meta-analytic methods. They found that some of these medications outperformed others in patient response to treatment. However, several methodological criticisms have been raised about network meta-analysis and Cipriani’s analysis in particular which creates the concern that the stated superiority of some antidepressants relative to others may be unwarranted. Materials and Methods: A Monte Carlo simulation was conducted which involved replicating Cipriani’s network metaanalysis under the null hypothesis (i.e., no true differences between antidepressants). The following simulation strategy was implemented: (1) 1000 simulations were generated under the null hypothesis (i.e., under the assumption that there were no differences among the 12 antidepressants), (2) each of the 1000 simulations were network meta-analyzed, and (3) the total number of false positive results from the network meta-analyses were calculated. Findings: Greater than 7 times out of 10, the network meta-analysis resulted in one or more comparisons that indicated the superiority of at least one antidepressant when no such true differences among them existed. Interpretation: Based on our simulation study, the results indicated that under identical conditions to those of the 117 RCTs with 236 treatment arms contained in Cipriani et al.’s meta-analysis, one or more false claims about the relative efficacy of antidepressants will be made over 70% of the time. As others have shown as well, there is little evidence in these trials that any antidepressant is more effective than another. The tendency of network meta-analyses to generate false positive results should be considered when conducting multiple comparison analyses.

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Concentrations of stable and radioactive nuclides produced by cosmic ray particles in meteorites allow us to track the long term average of the primary flux of galactic cosmic rays (GCR). During the past ∼10 Ma, the average GCR flux remained constant over timescales of hundreds of thousands to millions of years, and, if corrected for known variations in solar modulation, also during the past several years to hundreds of years. Because the cosmic ray concentrations in meteorites represent integral signals, it is difficult to assess the limits of uncertainty of this statement, but they are larger than the often quoted analytical and model uncertainties of some 30%. Time series of concentrations of the radionuclide 10Be in terrestrial samples strengthen the conclusions drawn from meteorite studies, indicating that the GCR intensity on a ∼0.5 million year scale has remained constant within some ±10% during the past ∼10 million years. The very long-lived radioactive nuclide 40K allows to assess the GCR flux over about the past one billion years. The flux over the past few million years has been the same as the longer-term average in the past 0.5–1 billion years within a factor of ∼1.5. However, newer data do not confirm a long-held belief that the flux in the past few million years has been higher by some 30–50% than the very long term average. Neither does our analysis confirm a hypothesis that the iron meteorite data indicate a ∼150 million year periodicity in the cosmic ray flux, possibly related to variations in the long-term terrestrial climate.

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The study that aimed at understanding the dynamics of forced livestock movements and pastoral livelihood and development options was conducted in Lindi and Ruvuma regions, using both formal and informal approaches. Data were collected from 60 randomly selected Agro-pastoralists/Pastoralists and native farmers using a structured questionnaire. Four villages were involved; two in Lindi region (Matandu and Mkwajuni) and the other two in Ruvuma region (Gumbiro and Muhuwesi). Data were analyzed using descriptive statistics of SPSS to generate means and frequencies. The results indicate that a large number of animals moved into the study area following the eviction order of the government in Ihefu wetlands in 2006/2007. Lindi region was earmarked by the government to receive all the evicted pastoralists. However, by 2008 only 30% of the total cattle that were expected to move into the region had been received. Deaths of many animals on transit, selling of the animals to pay for transportation and other costs while on transit and many pastoralists settling in Coastal and Ruvuma regions before reaching their destinations were reported to be the reasons for the discrepancy observed. To mitigate anticipated conflicts between farmers and pastoralists, Participatory Land Use Management (PLUM) plans were developed in all the study villages in order to demarcate village land area into different uses, including grazing, cropping, settlement and forests. Land units for grazing were supposed to be provided with all necessary livestock infrastructures (dips, charcoal dams, livestock markets and stock routes). However, the land use plans were not able to prevent the anticipated conflicts because most of the livestock infrastructures were lacking, the land use boundaries were not clearly demarcated and there was limited enforcement of village by-laws, since most had not been enacted by the respective district councils. Similarly, the areas allocated for grazing were inadequate for the number of livestock available and thus the carrying capacity exceeded. Thus, land resource-based conflicts between farmers and pastoralists were emerging in the study areas for the reason that most of the important components in the PLUM plans were not in place. Nevertheless, the arrival of pastoralists in the study areas had positive effects on food security and growth of social interactions between pastoralists and farmers including marriages between them. Environmental degradations due to the arrival of livestock were also not evident. Thus, there is a need for the government to purposely set aside enough grazing land with all necessary infrastructures in place for the agro-pastoral/pastoral communities in the country.

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STUDY OBJECTIVE Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. DESIGN Retrospective case-control study. SETTING A recent study showed that over 76% of significant genome-wide association variants lie within DNase I hypersensitive sites (DHSs). From our previous GWAS, we identified 30 single nucleotide polymorphisms (SNPs) with P < 10(-4) mapping to DHSs. Ten SNPs tagging these sites, HLADQB1, and all previously reported SNPs significantly associated with narcolepsy were tested for replication. PATIENTS AND PARTICIPANTS For GWAS, 1,261 narcolepsy patients and 1,422 HLA-DQB1*06:02-matched controls were included. For HLA study, 1,218 patients and 3,541 controls were included. MEASUREMENTS AND RESULTS None of the top variants within DHSs were replicated. Out of the five previously reported SNPs, only rs2858884 within the HLA region (P < 2x10(-9)) and rs1154155 within the TRA locus (P < 2x10(-8)) replicated. DQB1 typing confirmed that DQB1*06:02 confers an extraordinary risk (odds ratio 251). Four protective alleles (DQB1*06:03, odds ratio 0.17, DQB1*05:01, odds ratio 0.56, DQB1*06:09 odds ratio 0.21, DQB1*02 odds ratio 0.76) were also identified. CONCLUSION An overwhelming portion of genetic risk for narcolepsy with cataplexy is found at DQB1 locus. Since DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.

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STUDY QUESTION To what extent do the management of endometriosis and the symptoms that remain after treatment affect the quality of life in women with the disease? SUMMARY ANSWER Many women with endometriosis had impaired quality of life and continued to suffer from endometriosis-associated symptoms even though their endometriosis has been managed in tertiary care centres. WHAT IS KNOWN ALREADY The existing literature indicates that quality of life and work productivity is reduced in women with endometriosis. However, most studies have small sample sizes, are treatment related or examine newly diagnosed patients only. STUDY DESIGN, SIZE, DURATION A cross-sectional questionnaire-based survey among 931 women with endometriosis treated in 12 tertiary care centres in 10 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Women diagnosed with endometriosis who had at least one contact related to endometriosis-associated symptoms during 2008 with a participating centre were enrolled into the study. The study investigated the effect of endometriosis on education, work and social wellbeing, endometriosis-associated symptoms and health-related quality of life, by using questions obtained from the World Endometriosis Research Foundation (WERF) GSWH instrument (designed and validated for the WERF Global Study on Women's Health) and the Short Form 36 version 2 (SF-36v2). MAIN RESULTS AND THE ROLE OF CHANCE Of 3216 women invited to participate in the study, 1450 (45%) provided informed consent and out of these, 931 (931/3216 = 29%) returned the questionnaires. Endometriosis had affected work in 51% of the women and affected relationships in 50% of the women at some time during their life. Dysmenorrhoea was reported by 59%, dyspareunia by 56% and chronic pelvic pain by 60% of women. Quality of life was decreased in all eight dimensions of the SF-36v2 compared with norm-based scores from a general US population (all P < 0.01). Multivariate regression analysis showed that number of co-morbidities, chronic pain and dyspareunia had an independent negative effect on both the physical and mental component of the SF-36v2. LIMITATIONS, REASONS FOR CAUTION The fact that women were enrolled in tertiary care centres could lead to a possible over-representation of women with moderate-to-severe endometriosis, because the participating centres typically treat more complex and referred cases of endometriosis. The response rate was relatively low. Since there was no Institute Review Board approval to do a non-responder investigation on basic characteristics, some uncertainty remains regarding the representativeness of the investigated population. WIDER IMPLICATIONS OF THE FINDINGS This international multicentre survey represents a large group of women with endometriosis, in all phases of the disease, which increases the generalizability of the data. Women still suffer from frequent symptoms, despite tertiary care management, in particular chronic pain and dyspareunia. As a result their quality of life is significantly decreased. A patient-centred approach with extensive collaboration across disciplines, such as pain specialists, psychologists, sexologists and social workers, may be a valuable strategy to improve the long-term care of women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The WERF EndoCost study is funded by the World Endometriosis Research Foundation (WERF) through grants received from Bayer Schering Pharma AG, Takeda Italia Farmaceutici SpA, Pfizer Ltd and the European Society of Human Reproduction and Embryology. The sponsors did not have a role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. L.H. is the chief executive and T.D. was a board member of WERF at the time of funding. T.D. holds the Merck-Serono Chair in Reproductive Medicine and Surgery, and the Ferring Chair in Reproductive Medicine at the Katholieke Universiteit Leuven in Belgium and has served as consultant/research collaborator for Merck-Serono, Schering-Plough, Astellas and Arresto.

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Previous syntheses on the effects of environmental conditions on the outcome of plant-plant interactions summarize results from pairwise studies. However, the upscaling to the community-level of such studies is problematic because of the existence of multiple species assemblages and species-specific responses to both the environmental conditions and the presence of neighbors. We conducted the first global synthesis of community-level studies from harsh environments, which included data from 71 alpine and 137 dryland communities to: (i) test how important are facilitative interactions as a driver of community structure, (ii) evaluate whether we can predict the frequency of positive plant-plant interactions across differing environmental conditions and habitats, and (iii) assess whether thresholds in the response of plant-plant interactions to environmental gradients exists between ``moderate'' and ``extreme'' environments. We also used those community-level studies performed across gradients of at least three points to evaluate how the average environmental conditions, the length of the gradient studied, and the number of points sampled across such gradient affect the form and strength of the facilitation-environmental conditions relationship. Over 25% of the species present were more spatially associated to nurse plants than expected by chance in both alpine and chyland areas, illustrating the high importance of positive plant-plant interactions for the maintenance of plant diversity in these environments. Facilitative interactions were more frequent, and more related to environmental conditions, in alpine than in dryland areas, perhaps because drylands are generally characterized by a larger variety of environmental stress factors and plant functional traits. The frequency of facilitative interactions in alpine communities peaked at 1000 mm of annual rainfall, and globally decreased with elevation. The frequency of positive interactions in dtyland communities decreased globally with water scarcity or temperature annual range. Positive facilitation-drought stress relationships are more likely in shorter regional gradients, but these relationships are obscured in regions with a greater species turnover or with complex environmental gradients. By showing the different climatic drivers and behaviors of plant-plant interactions in dryland and alpine areas, our results will improve predictions regarding the effect of facilitation on the assembly of plant communities and their response to changes in environmental conditions.

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The distributions of event-by-event harmonic flow coefficients v_n for n=2-4 are measured in sqrt(s_NN)=2.76 TeV Pb+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using charged particles with transverse momentum pT> 0.5 GeV and in the pseudorapidity range |eta|<2.5 in a dataset of approximately 7 ub^-1 recorded in 2010. The shapes of the v_n distributions are described by a two-dimensional Gaussian function for the underlying flow vector in central collisions for v_2 and over most of the measured centrality range for v_3 and v_4. Significant deviations from this function are observed for v_2 in mid-central and peripheral collisions, and a small deviation is observed for v_3 in mid-central collisions. It is shown that the commonly used multi-particle cumulants are insensitive to the deviations for v_2. The v_n distributions are also measured independently for charged particles with 0.51 GeV. When these distributions are rescaled to the same mean values, the adjusted shapes are found to be nearly the same for these two pT ranges. The v_n distributions are compared with the eccentricity distributions from two models for the initial collision geometry: a Glauber model and a model that includes corrections to the initial geometry due to gluon saturation effects. Both models fail to describe the experimental data consistently over most of the measured centrality range.

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Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synthesis of choline-­containing phospholipids, such as phosphatidylcholine (PC). Our experiments showed – for the first time – that Trypanosoma brucei, the causative agent of human African sleeping sickness, is able to take up choline from the culture medium to use for PC synthesis, indicating that trypanosomes express a transporter for choline at the plasma membrane. Further characterization in procyclic and bloodstream forms revealed that choline uptake is saturable and can be inhibited by HC-3, a known inhibitor of choline uptake in mammalian cells. To obtain additional insights on choline uptake and metabolism, we investigated the effects of choline-analogs that were previously shown to be toxic for T. brucei parasites in culture. Interestingly, we found that all analogs tested effectively inhibited choline uptake into both bloodstream and procyclic form parasites. Subsequently, selected compounds were used to search for possible candidate genes encoding choline transporters in T. brucei, using an RNAi library in bloodstream forms. We identified a protein belonging to the mitochondrial carrier family, previously annotated as TbMCP14, as prime candidate. Down‐regulation of TbMCP14 by RNAi prevented drug-­induced loss of mitochondrial membrane potential and conferred 8­‐fold resistance of T. brucei bloodstream forms to choline analogs. Conversely, over‐expression of the carrier increased parasite susceptibility more than 13-­fold. However, subsequent experiments demonstrated that TbMCP14 was not involved in metabolism of choline. Instead, growth curves in glucose‐depleted medium using RNAi or knock‐out parasites suggested that TbMCP14 is involved in metabolism of amino acids for energy production. Together, our data demonstrate that the identified member of the mitochondrial carrier family is involved in drug uptake into the mitochondrion and has a vital function in energy production in T. brucei.

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BACKGROUND The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system. METHODS Pubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed. RESULTS Out of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception. CONCLUSIONS Our findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture.

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BACKGROUND Over 80% of strokes result from ischemic damage to the brain due to an acute reduction in the blood supply. Around 25-35% of strokes present with large vessel occlusion, and the patients in this category often present with severe neurological deficits. Without early treatment, the prognosis is poor. Stroke imaging is critical for assessing the extent of tissue damage and for guiding treatment. SUMMARY This review focuses on the imaging techniques used in the diagnosis and treatment of acute ischemic stroke, with an emphasis on those involving the anterior circulation. Key Message: Effective and standardized imaging protocols are necessary for clinical decision making and for the proper design of prospective studies on acute stroke. CLINICAL IMPLICATIONS Each minute without treatment spells the loss of an estimated 1.8 million neurons ('time is brain'). Therefore, stroke imaging must be performed in a fast and efficient manner. First, intracranial hemorrhage and stroke mimics should be excluded by the use of computed tomography (CT) or magnetic resonance imaging (MRI). The next key step is to define the extent and location of the infarct core (values of >70 ml, >1/3 of the middle cerebral artery (MCA) territory or an ASPECTS score ≤ 7 indicate poor clinical outcome). Penumbral imaging is currently based on the mismatch concept. It should be noted that the penumbra is a dynamic zone and can be sustained in the presence of good collateral circulation. A thrombus length of >8 mm predicts poor recanalization after intravenous thrombolysis.

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The direct Bayesian admissible region approach is an a priori state free measurement association and initial orbit determination technique for optical tracks. In this paper, we test a hybrid approach that appends a least squares estimator to the direct Bayesian method on measurements taken at the Zimmerwald Observatory of the Astronomical Institute at the University of Bern. Over half of the association pairs agreed with conventional geometric track correlation and least squares techniques. The remaining pairs cast light on the fundamental limits of conducting tracklet association based solely on dynamical and geometrical information.

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UNLABELLED Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

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This paper presents the performance of the ATLAS muon reconstruction during the LHC run with pp collisions at √s = 7–8 TeV in 2011–2012, focusing mainly on data collected in 2012. Measurements of the reconstruction efficiency and of the momentum scale and resolution, based on large reference samples of J/ψ → μμ, Z → μμ and ϒ → μμ decays, are presented and compared to Monte Carlo simulations. Corrections to the simulation, to be used in physics analysis, are provided. Over most of the covered phase space (muon |η| < 2.7 and 5 ≲ pT ≲ 100 GeV) the efficiency is above 99% and is measured with per-mille precision. The momentum resolution ranges from 1.7% at central rapidity and for transverse momentum pT ≅ 10 GeV, to 4% at large rapidity and pT ≅ 100 GeV. The momentum scale is known with an uncertainty of 0.05% to 0.2% depending on rapidity. A method for the recovery of final state radiation from the muons is also presented.

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Preferentialism and multilateralism are not two independent and succinct avenues in the pur-suit of market access and regulatory policies. They historically build upon each other in a dialectical process, closely related and linked through regulatory bridges and references. They influence and direct each other in various ways. The paper mainly focuses on the evolution of international protection of intellectual property rights and of services. The multilateral regulation of the TRIPS and others derive from years of regulatory experience and high numbers of preferential agreements across the globe. The GATS and others, on the other hand, have entered the pluri- or multilateral stage early. Once regulation has reached the mul-tilateral stage, preferentialism focuses on WTO-plus and -extra commitments. Both areas, however, show close interaction. The principle of MFN ensures that multilateralism and preferentialism do not evolve independently from each other. It produces significant spill-over effects of preferential agreements. Such effects and the need to develop uniform and coherent regulatory standards have led in parallel to a number of preferential, plurilateral and multilateral regulatory initiatives. We submit that the process will eventually encourage the return to multilateralism and negotiations in international fora, in particular the WTO while traditional market access may stay with preferential relations among Nations. Such burden-sharing between different regulatory fora should be reflected in future WTO rules providing the overall backbone of the system.