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Fezzaa is adjusting the nozzle of a commercial paint spray gun tions, in that the breakups are utilized to generate a coaxial air-assisted water spray that is imaged within the first 10-20 mm of controlled by a competition the nozzle exit. Windows (holes) in the acrylic cylinder behind his hand let the x-ray beam pass between aerodynamic forces and without going through the plastic. The cylinder contains the water and is designed to minimize back the surface tension of the liquid. Fezzaa notes that this the complexity of jet breakup experiment, and the problem of how two droplets of liquid coalesce to form one drop, are examhas been a daunting obstacle to ples of relatively old questions that are being answered with the use of fairly simple apparatus research progress. For more on droplet similarities the researchers found coalescing, see "How Two Drops Become One" on page 36. Correspondence: processes, and among primary As the air speed continued to *fezzaa@aps. A increase, the surface undulations commercial paint spray-gun was used became amplified as they moved this research and the use of the Advanced to generate the coaxial air-assisted downstream, and formed rod-like strucPhoton Source were supported by the U. The x-rays transmitted tures protruding into the airstream, Department of Energy, Office of Science, and diffracted through the jet were conwhich broke away from the jet when Office of Basic Energy Sciences, under verted to visible light by a scintillating the air speed reached 50. The breakup process was stretched to form long ligaments that science · Phase-contrast imaging, studied by using a combination of sinsubsequently broke up. The scientists ultra-small-angle x-ray scattering, radigle-exposure and multiple-exposure noted that the transition from rod-like ography · 3. These processes strongly affect the diffusive flux of dissolved organic carbon, which can potentially transform to greenhouse gases. The organic coating can also change the reactive properties of mineral surfaces and influence the environmental distribution, speciation, and bioavailability of metals and organic pollutants. But soft organic matter is often difficult to image when wet, and drying may alter the original structure of organic molecules adsorbed on a surface. X-ray reflectivity, however, is an attractive method for overcoming this difficulty because it is non-invasive and can be applied in solution, making it a good choice for in situ investigations of soft organic films adsorbed on mineral surfaces. Schematic showing the sequence of steps used to determine the interfacial structure from measured x-ray reflectivity data. The x-ray photon beam from a synchrotron insertion device (bottom, right) strikes a muscovite basal surface in a fulvic acid solution represented by the molecular scale model (bottom, middle) and is reflected to a chargecoupled device area detector (bottom, left). Reflected intensities are measured as a function of momentum transfer, q (top left), and the curves are transformed into electron-density profiles as a function of height above the muscovite surface (top right). The electron-density profiles show that the sorbed fulvic acid forms a 6-Е- to 12-Е-thick film (bottom, middle) at pH 2 to 6, whereas the film disappears at pH 8. The team developed a new model to extract the electron density distribution at the interface from the reflectivity data. The model contained three components: (1) ideal muscovite substrate lattice; (2) interfacial species, including relaxed muscovite surface layers and any additional layers of surface adsorbed species; and (3) bulk water above the surface. This was followed by a broad profile obtained from the summation of multiple, overlapping Gaussian peaks that diminished in electron density as the distance to the surface increased. Nagy1, "Fulvic Acid Sorption on Muscovite Mica as a Function of pH and Time Using In Situ X-ray Reflectivity," Langmuir 24, 7817 (2008). Glass is an odd substance: definitely not gaseous, not quite solid, not quite liquid, but something in between. By confirming predictions from recent theories about the transition of liquids to glass, their work might make glass a bit less mysterious. A partially coherent x-ray beam scattered from the sample produced a speckle pattern, from which the behavior of particles in the sample could be inferred. As expected, the team found that, upon cooling, the mixture underwent a transition from liquid to what is called a "repulsion-dominated" glass, in which each particle is surrounded, or caged, by its neighbors. As the caging particles attract each other, the trapped particles are released, and the structure breaks down. Unlike the lower-temperature transition, in which particles are caged by one another- with everything keeping a respectful distance from everything else-in this new attraction-dominated structure, the particles are crunched together, squelching the free-motion characteristics of a liquid state. In between the two glass transitions, the intermediate liquid state obeys unusual logarithmic time dependence of the relaxations. While other experiments using different techniques have shown similar phenomena, they required tedious procedures, such as precisely mixing samples, in order to alter the attraction strength. In the current work, the researchers did not have to do anything more complicated than turning up the heat.

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Nevertheless a tendency to unstructured proteins was observable with increasing number of substitutions. Native-type protein folding is essential for studying influence of amino acid substitutions on IgE binding because an altered protein conformation often reduces binding of serum IgE (Holm et al. Therefore introduced amino acid substitutions influenced protein expression and caused an increase in formation of inclusion bodies. In both assays a reduction in IgE signals compared to native Gly m 4 was observable. Majority of patients (94%, 15/16) analyzed with rGly m 4 11x in immunoblot showed a reduced IgE binding, while only one patient with comparable IgE signals could be identified. At least some of substituted residues might represent amino acids crucial for IgE binding and are part of one or more epitopes on Gly m 4. Nevertheless further epitopes need to be present because, as expected, eleven substitutions did not reduce IgE signal completely in all patients. Especially patient 11, not responding to any of introduced residues might contain IgE antibodies directed solely against epitopes different from ones addressed with rGly m 4 11x. In contrast a decrease in IgE binding was observed with rGly m 4 9x, 10x, 11x and 14x as inhibitors. Often with increasing number of substitutions a stronger decrease in IgE signals was observable. Additional information on IgE inhibition potency of used variants might be achieved using dose-related inhibitions rather than single inhibitor concentrations but substituted residues contributed at least to some extend to binding of IgEs. In none of studied patients a complete reduction of IgE binding was possible with any of the used inhibitors. This emphasizes the presence of further IgE epitopes still allowing interaction with IgE antibodies. K32 and D60 were also substituted in rGly m 4 9x whereas all three residues were changed to alanine in rGly m 4 variants 10x, 11x and 14x. Therefore D27, K32 and D60 might play a key role in binding of IgE antibodies probably due to their surface-exposed position or their charged side chains enabling for easy interaction with antibody ligands. In this study 18 putative functional IgE epitopes could be identified but usage of multiple substitutional rGly m 4 variants requires further experiments to verify importance of each single amino acid. Nevertheless, generated variants can be used anyway as a basis for thorough studies on IgE epitope profile. Different IgE antibodies might bind epitopes on allergen surface with a range of affinities. Several high affinity epitopes are for example known for peanut allergen Ara h 3 and melon allergen Cuc m 2 (Rougй et al. In this study, both groups of patients with and without birch-related soybean allergy were analyzed according to differences in IgE avidity (see 3. For this, binding between IgE and rGly m 4 was inhibited with rGly m 4 and the misfolded variant rGly m 4S111P/L150P. Overall no differences in avidity were observable between both groups of patients regarding each allergen. This is in line with analysis of misfolded rGly m 4S111P/L150P exhibiting IgE binding with several patients of study population. For rGly m 4 an increase in IgE avidity might not be relevant for outbreak of soybean allergy in the study population. Rather affinity of specific IgE epitopes should be considered in combination with patient-specific IgE epitope profile. High affinity epitopes causing allergic symptoms might be present 4 Discussion 135 only in patients with clinical allergy while patients sensitized but not allergic to soy show no immunodominant epitopes. Therefore thorough analysis of IgE epitopes and their antibody affinities might be useful to determine allergic potential. In basic research rBet v 1a is often used as reference material for biological and physicochemical analysis with its well established purification protocol also existing for rGly m 4. For diagnostic purpose and laboratory use a consistent quality of both allergen preparations needs to be maintained. In this study I analyzed the physicochemical and immunological characteristics of both rBet v 1a and rGly m 4 and the influence of different molar ratios of a respective misfolded variant concerning structure and IgE binding ability (see 3. With this, a correlation between experimental and theoretically expected data for both allergen combinations is possible. Furthermore the precision according to the confidence intervals of 95% chosen with the actual IgE binding protein moiety is resolved quantitatively by the respective analytical method.

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Marijuana users are many times more likely than non-users to progress to hard drug use. Almost all who have used marijuana and hard drugs have used marijuana first (Yamaguchi and Kandel, 1984) 3. The greater the frequency of marijuana use, the greater the likelihood of using marijuana later. Cannabis use is illegal so supplies come from the illegal market, bringing exposure of young people to drug dealers. Dr Patrick Dixon in his book the Truth About Drugs (1998), says, "Common sense tells us there is a link. We know that once teenagers start smoking tobacco it is easier for them to cross the next step and smoke cannabis". Someone had something else so for a bit of a laugh we all tried it" "It is dangerous nonsense therefore to suggest that cannabis use does not significantly increase the risk of a serious drug addiction later on" (Dixon, 1998). The "personality and background predisposition hypothesis" was explored by Degenhardt and others in 2001. There was a small group with anti-social behaviour, another with low self-esteem and poor relationships with their parents and friends, the third group were "ordinary". Users of tobacco and alcohol were more likely than non-users to have the opportunity to try marijuana and indeed were more likely to take it. Among the young people who had a "cocaine opportunity", those who had used marijuana were more likely to use cocaine than those with no previous history of using cannabis. Within one year of "exposure" two-thirds of the cannabis-users had tried it, but only 1 in 6 of those who had never smoked cannabis (Wagner and Anthony, 2002). In 2003, Lynskey and others examined 311same-sex twins (identical and non-identical) in Australia. The twin using cannabis before 17 had odds of other drug use, alcohol dependence and drug use/dependence that were 2. Controlling for early alcohol or tobacco use, parental conflict/separation, childhood sex abuse, conduct disorder, major depression and social anxiety had negligible effects of the outcome. So common environmental and genetic influences seemed not to be predisposition factors. Association with different peers and the social contexts in which cannabis was used may have some bearing on the results. They concluded: Early cannabis use is strongly associated with other illicit drug use and abuse/dependence. The relationship arises largely due to correlated genetic and environmental influences with persisting evidence for some causal influences. In 2006 Lynskey, again with a team, conducted research into twins this time of Dutch nationality, 219 same-sex pairs, discordant for cannabis use before 18 were used. The rates of lifetime party drug use, use of hard drugs, but not regular cannabis use, were significantly higher in the pre18 using twin. Again this suggested that the progression seen is not explained by common familial risk factors, genetic or environmental. Professor David Fergusson and his teams have conducted a long-term longitudinal study in New Zealand, the Christchurch Health and Development Study. They have been regularly assessed till the age of 21 with an 80% follow-up (Fergusson et al, 1997, 2000, 2002). However at 21, more data were available and methods of analysis were more advanced. For young 14 to 15 year old heavy consumers a very strong association existed even after controlling for other suspected or known causal factors. It was the first time such a strong connection had been seen (Fergusson et al, 2002). Those using cannabis on 750 occasions/year had hazards of other illicit drug use 59. After adjustments for co-variants, childhood, family and adolescent lifestyle factors, the association was still remarkably strong. Nonetheless the possibility remains that the association is non-causal and reflects factors that were not adequately controlled in the analysis". The sequence of events he said could suggest a cause and effect relationship where the use of cannabis encourages the use of other illicit drugs.

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A 10-year prospective study of single tooth implants placed in the anterior maxilla. Technical and biological complications/failures with single crowns and fixed partial dentures on implants: a 10-year prospective cohort study. Marginal bone preservation in single-tooth replacement: a 5-year prospective clinical multicenter study. Anterior single implants with different neck designs: 5 year results of a randomized clinical trial. Oral health-related quality of life changes after placement of immediately loaded single implants in healed alveolar ridges or extraction sockets: a 5-year prospective follow-up study. Single-tooth rehabilitations supported by dental implants used in an immediate-provisionalization protocol: report on long-term outcome with retrospective follow-up. Systematic review of the survival rate and the incidence of biological, technical, and aesthetic complications of single crowns on implants reported in longitudinal studies with a mean follow-up of 5 years. Interventions for replacing missing teeth: different times for loading dental implants. Replacement of missing posterior tooth with off-center placed single implant: Long-term follow-up outcomes. Prosthetic survival and complication rate of single implant treatment in the periodontally healthy patient after 16 to 22 years of follow-up. Evaluation of aesthetics of implant-supported single-tooth replacements using different bone augmentation procedures: a prospective randomized clinical study. Outcome evaluation of early placed maxillary anterior single-tooth implants using objective esthetic criteria: a cross-sectional, retrospective study in 45 patients with a 2- to 4-year follow-up using pink and white esthetic scores. Oral healthrelated quality of life and esthetic outcome in single anterior maxillary implants. A retrospective evaluation of aesthetic outcomes for single-tooth implants in the anterior maxilla. Factors affecting soft tissue level around anterior maxillary single-tooth implants. The impact of buccal bone defects and immediate placement on the esthetic outcome of maxillary anterior single-tooth implants. The writing is exposed on 240 pages with affirmative material presented in 49 tables, 44 figures, 12 clinical cases, 4 annexes, and a bibliography citing 340 scientific sources. The work begins with Introduction where is elucidated the actuality of the subject studied and are outlined the purpose and objectives of this research. In the first chapter is analyzed the complex vision in the evolution of toxocariasis according to current literature. There are presented epidemiological aspects and trends in the world, the factors identifying increased degrees of infestation. The pathogenic specificity, complemented by modern explorations and multiplicity of clinical manifestations are analyzed. The need for further studies on toxocariasis and the accumulation of new data in diagnosis, therapy, and prevention are highlighted. The third chapter is devoted to the identification of the factors that influence the increased toxocariasis seroprevalence in the Republic of Moldova, which is one of the highest in the world - 58. Direct correlation between peak levels of toxocariasis antibody levels, addressability and admission (P <0. The author has shown that in the acute evolution of toxocariasis the larvae migrans visceralis syndrome manifests only in 21. The evolution differences in toxocariasis with mono-invasion and toxocariasis with different comorbidities are clear, with a clearly superior prevalence of toxocariasis injury versus associated parasitoses. Chapter V establishes clinical and laboratory determinants in the different evolution of chronic toxocariasis. Thus, early cure in the first year of monitoring and timely therapy only occurs in 5.

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A dose of 5 g idarucizumab will be administered intravenously to reverse the effect of dabigatran. The trial will measure plasma-diluted thrombin time and ecarin clotting time as primary outcome measures. It has been developed as an antidote to reverse anticoagulant activity of oral direct. The current guideline recommendation is to extend thromboprophylaxis to 35 days from the day of surgery. Serial imaging of the deep veins in 2 weeks when there are no severe symptoms or risk for extension. We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Grade 2B), and recommend treatment for 3 months over extended therapy if there is a high risk of bleeding (Grade 1B). Remarks: Patient sex and D-dimer level measured a month after stopping anticoagulant therapy may influence the decision to stop or extend anticoagulant therapy (see text). In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals. Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals. Remarks: In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually). Use of aspirin should also be reevaluated when patients stop anticoagulant therapy because aspirin may have been stopped when anticoagulants were started. Remarks: Patients at high risk for bleeding are more likely to benefit from serial imaging. Patients who place a high value on avoiding the inconvenience of repeat imaging and a low value on the inconvenience of treatment and on the potential for bleeding are likely to choose initial anticoagulation over serial imaging. Patients and physicians are more likely to opt for clinical surveillance over anticoagulation if there is good cardiopulmonary reserve or a high risk of bleeding. Development of hypotension suggests that thrombolytic therapy has become indicated. Remarks: Catheter-assisted thrombus removal refers to mechanical interventions, with or without catheter directed thrombolysis. Even though it was a non-inferiority study, the final analysis showed dabigatran to be superior to warfarin. Both low-dose and high-dose dabigatran were associated with a statistically significant increase in rate of myocardial infarction (0. Which of the following antiplatelets would be best to start in combination with aspirin 324 mg in this patient for prevention of stent thrombosis? What is the proposed rationale behind avoiding concomitant use of ticagrelor with aspirin doses above 100 mg per day? Concomitant use of ticagrelor and aspirin >100 mg daily may result in decreased efficacy of aspirin B. Concomitant use of ticagrelor and aspirin >100 mg daily may result in decreased efficacy of ticagrelor C. Concomitant use of ticagrelor and aspirin >100 mg daily may result in intolerable gastrointestinal adverse events that may lead to drug discontinuation D. Concomitant use of ticagrelor and aspirin >100 mg daily may result in increased hypersensitivity to aspirin 3. She has been on long-term warfarin therapy for secondary stroke prevention with a history significant for atrial fibrillation and ischemic stroke (2011). You would like to consider transitioning her to rivaroxaban as this is what her insurance company will cover. Discontinue warfarin; start rivaroxaban after 3­5 days of discontinuation of warfarin D. Labs from his current admission observe notable increases in blood urea nitrogen/serum creatinine and decreased urine output, suggesting signs of acute kidney injury. Which of the following intravenous antiplatelet inhibitors would be best to use if the patient is found to require emergency coronary artery bypass grafting surgery? He presented to the hospital with sharp, crushing chest pain, shortness of breath, and fatigue. After 4 weeks, stop aspirin and continue clopidogrel 75 mg daily for at least 12 months D.

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The company discloses via the Index partial information about the registration status of its most recently launched products* that target diseases within the scope of the Index in countries within the scope of the Index. Per disease, the set of priority countries includes five low-income countries (World Bank defined) in order to ensure the Index evaluates pricing strategies directed towards poorer countries. Companies with less than average number of products within the scope of the Index that have equitable pricing strategies: for the majority of its products that have an inter-country equitable pricing strategy, the company takes into account affordability and demonstrate the applied use of some socioeconomic factors. Among these products, the average number of socioeconomic factors taken into account per product is 5. Companies with less than 15 products within the scope of the Index that have equitable pricing strategies: for the majority of its products that have an inter-country equitable pricing strategy, the company takes into account affordability and some socioeconomic factors. Companies with less than the average number of products within the scope of the Index that have equitable pricing strategies: for the majority of its products that have an inter-country equitable pricing strategy, the company takes into account affordability and some socioeconomic factors. Among these products, the average number of socioeconomic factors taken into account per product is 1. Companies with less than the average number of products within scope of the Index that have equitable pricing strategies: for the majority of its products that have an inter-country equitable pricing strategy, the company takes into account affordability and demonstrate an applied use of some socioeconomic factors. Among these products, the average number of socioeconomic factors taken into account per product is 1-2. Among these products, the average number of socioeconomic factors taken into account per product is 4. Companies with less than 15 products within the scope of the Index that have equitable pricing strategies: for the majority of its products that have an intra-country equitable pricing strategy, the company takes into account affordability and some socioeconomic factors. Among these products, the average number of socioeconomic factors taken into account per product is 2. Among these products, the average number of socioeconomic factors taken into account per product is 3. The company has inter-country equitable pricing strategies but no intra-country equitable pricing strategies for its products that target diseases within the scope of the Index. The company has filed to register the some of its most recently launched products* that target diseases in scope, in the minority of corresponding priority countries. Per disease, the set of priority countries includes five low-income countries (World Bank defined) in order to ensure the Index evaluates pricing strategies directed towards poorer countries 241 Access to Medicine Index 2018 ­ Appendices D. The company also has processes specifically to track products in countries within the scope of the Index to ensure effective recalls. The company provides no evidence of processes specifically to track products in countries within the scope of the Index to ensure effective recalls. This system involves: a) making efforts to understand product distribution and demand behaviour in countries in scope, beyond the point of first product hand-off; b) applying this information to ensure sufficient, timely supply to these countries; and c) specific efforts to address supply to Least Developed Countries, low income countries, and/or poor and rural population segments in countries within the scope of the Index. This system involves: 1) making efforts to understand product distribution and demand behaviour in countries in scope, beyond the point of first product hand-off; and 2) applying this information to ensure sufficient, timely supply to these countries. The company provides no evidence of specific efforts to address supply to Least Developed Countries, low income countries, and/or poor and rural population segments in countries within the scope of the scope of the Index. Approaches focusing on equitable pricing target those who face the highest financial barriers to access. Only innovative projects for which either progress made, or human and/or financial resources are disclosed, are taken into consideration. The company has issued voluntary licences which include all Least Developed Countries, all low income countries, all of SubSaharan Africa, and 6 to 10 of the middle income countries with the ten highest burdens of disease outside of sub-Saharan Africa. The company has issued voluntary licences which include all Least Developed Countries, all low income countries, all of SubSaharan Africa, and 1 to 5 of the middle income countries with the highest burdens of disease outside of sub-Saharan Africa. The company does not include in its voluntary licences any of the middle income countries with the ten highest burdens of disease outside of sub-Saharan Africa. The company includes an average of four to five of the designated access-oriented clauses* in the terms of the voluntary licences it has agreed for products relevant to the Index, in countries relevant to the Index. The company provides evidence that it includes an average of two to three of the designated access-oriented clauses* in the terms of the voluntary licences it has agreed for products relevant to the Index, in countries relevant to the Index. The company discloses to/via the Index a detailed policy or approach for addressing falsified and/or substandard medicines in countries within the scope of the Index. These initiatives meet good practice standards* in countries within the scope of the Index. The company provided evidence of only one initiative in partnership with a local university or public research institution which addresses local needs that meets some or none of the other good practice standards. The company provided evidence of three to five health system strengthening initiatives done in partnership which address local needs and have processes in place to mitigate conflict of interest where only one of these initiatives met all additional good practice standards (see above).

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The 4 interviewed families had plots with houses sized 2900 m2, 2500 m2, 3000 m2 and 3000 m2. The plots were all registered in the name of the head of the family, who were all men. Besides these plots that they all reported to have official papers on, but did not know wher the actual official registration was, also had unregistered land plots were vegetables/potatoes and especially nuts were grown. The incomes on the land only were estimated to be app/annually: 12000, 30000 (had cattle), 15000 and 15000. Average plot size of the interview people in Tsetkhlauri (minus the cattle farmer) was approximately 1 ha of unregistered land (user right). Averaged reported income per ha is estimated to be: 17 400 (leaving out the cattle farmer, as this person had significantly higher annual turnover/ha). The 4 interviewed families did not feel they had been consulted and had not received sufficient information from the government. An inventory had been made by government officials last year, but since then the villagers had not received any new information. One demonstration was made in front of the Kobuleti municipality with approximately 70-80 people. Impact on crops Mitigation measure on social risks include, but is not limited to: - information disclosure orally and in writing, ensuring women are present at these meetings and have equal access to information. The visit revealed that findings have been made in Ajara region that dates back 300 000 years. Chance finds have been made mainly in Dmanisi (South-East Georgia), Gonio (Ajara, Khelvachauri region) and Pichvnari (Ajara, Kobuleti region). Both chance finds (reported as accidental finds) and finds from excavations are placed at the museum. Museum guide reported that the public as well as public/private organisations come in with chance finds and that they were paid for the artefacts that they founds. It was also the opinion of the museum staff that people in general had some sort of understanding that finds should be reported to the museum or the department for archaeology at the university. A stage 1 permit is being issued after recommendations by the Ministry of Culture who has made an ocular assessment. Potential impact from construction work cannot be said to be without possibilities to do chance finds. Although museum report that knowledge is high among people in general about the need to preserve artefacts, there is a slight risk that the matter is not dealth with in a proper way during construction works. All subcontracted consultants/companies should, in addition, be informed about chance find procedures and contracts should obligate precaution in relation to cultural heritage. The plan is that an access road will be built from the new highway passing to the landfill. It can be assumed that a temporary road for the construction period should be built or the current provisional road should be upgraded. The Consultant recommends building a construction road to avoid heavy transport on the existing village road. The construction road can be built avoiding settlements and join the existing asphalted road between the villages. The access road from the highway to the landfill would pass grassland and no residences are in the vicinity. In fact, the delineation of the access road is almost the same as the earth road used by the local people today for commuting between villages Ochkhmahuri and Tsetskhlauri. Road design will take traffic safety into consideration, including safety for pedestrians, donkey carts or cyclists. The power sub-station from where the necessary electricity can be supplied is on a distance of 2 km. It can be firmly stated that neither negative environmental nor social impacts cannot be expected from the construction or operation of these two facilities because they would stretch over the areas where no settlements can be found. Water supply of drinking purposes of the landfill will be ensured by a new artesian well to be installed. This well should also substitute the existing artesian well that provides water for some houses in the village.

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Companies can also evaluate opportunities to expand access initiatives already in place for products in this group to additional countries, so that more people can benefit, recognising that, as patent owners, they are in a strong position to influence who gains access to these important products, as well as a responsibility to take positive action. Challenges of access to medicine and the responsibility of pharmaceutical companies: a legal perspective. However, in many areas evaluated, a handful of companies account for most activity. Key areas for access continue to lag behind: in access planning, licensing and registration in priority countries. Many companies have also become more transparent about what products are under patent and where, with 17 out of the 20 now revealing this information. This shift has been influenced by years of external pressure and provides much needed clarity for international procurers supplying medicines to low-resource countries. Core groups of companies account for most activity All companies assessed are pursuing access initiatives to some degree. For instance, the majority of the R&D efforts that the global health community considers a priority is being performed by just five companies, while one-third of such priority R&D projects are carried out by a single company. Meanwhile, the increase identified in segmented pricing is being driven by just five of the companies, as is the application of access plans to candidate products in the pipeline. This reliance on a concentrated group to drive most of the activity makes the access ecosystem fragile; if any of these companies changed direction to focus exclusively on commercial markets in high-income countries, a large proportion of the contributions of the R&D-based industry to access to medicine would be at risk. Models for good practice emerge Key areas for access continue to lag behind, however models for good practice have emerged. Only 1 out of 5 candidate products in the late stage of development, across all disease categories, have access plans attached to them, such as registration plans for low- and middle-income countries and commitments to affordability. Nevertheless, five companies now have strong processes for systematically developing access plans. In addition, less than one-quarter of recently launched products have been filed for registration in the majority of countries the Index identifies as being particularly in need of them. Disease and country focus Emerging markets such as China, Brazil and India continue to get significant attention, particularly when it comes to the implementation of segmented pricing and product registration filings, and to transferring knowledge, expertise and other capacities to support the local manufacture of pharmaceutical products. Capacity building initiatives to strengthen health systems and supply chains are particularly concentrated in sub-Saharan Africa. In many areas, such as R&D and pricing, a handful of companies account for the bulk of the activity to address access to medicine in low- and middle-income countries. It leads a broad, mid-ranking pack of companies with close scores; this means small shifts in performance would lead to large changes in ranking. The Index credits compa- All companies were assessed based on data submitted to the Index in the current and previous periods of analysis, as well as information the companies have made publicly available, or that are accessible through other sources. In 2018, three companies declined to provide data to the Access to Medicine Index: AbbVie, Eli nies for placing information in the public domain that can support access to medicine, for example, information used by procurers and governments. They most consistently invest in projects that the global health community has identified as pressing priorities with either no or low commercial incentive. They frame access as a business proposition, and all are among the leaders in multiple areas of evaluation. It continues to outpace peers, supported by and building on its long-standing foundation of projects, initiatives and policies. Novartis rises one place to take second rank, having climbed every Index since 2012. Johnson & Johnson remains in the top three companies for the fourth consecutive Index. The company remains an access leader, with a robust internal structure for ensuring coherent, senior governance of access in selected disease areas, and a strong approach to capacity building that aligns with stakeholder expectations. The company has expanded its global health focus since 2016, for example to newly include mental health. The company has particular strength in targeting R&D priorities and in the systems it has in place to minimise the risk of corruption and unethical marketing. The Index uses dense ranking: all 20 companies are ranked, companies that compare equally receive the same ranking number. They lead a broad mid-ranking pack of companies stretching to Bristol-Myers Squibb in 15th place.

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In one community of 650 people, 30 suicide attempts related to cannabis were made in one year, in one month period, 3 succeeded. It appeared that they were buying marijuana, mixing it with alcohol and becoming paranoid. Research was carried out in the Caribbean island of Trinidad where there is an established use of cannabis and high suicide rates. Our findings suggest that there is a convincing relationship between suicidal behaviour and cannabis use"(Maharajh and Konings, 2005). Heavy cannabis use and depression were linked in a study on 3 Aboriginal communities in Arnhem Land in the Northern Territory in May 2008 by Lee and others. There have been numerous reports in the press linking cannabis with violent incidents and suicide. These are a few examples: A wealthy 52 year-old music producer was attacked in her home by a 20 year-old family friend made psychotic by the drug. A judge attacked the use of cannabis after a 25 year-old professional golfer with a history of cannabis smoking killed his grandmother and aunt in a frenzied attack (Daily Mail 25/11/03). A 52 year-old man grew his own supplies in his attic and had become addicted after smoking between 5 and 10 cannabis cigarettes a day. He shot his 66 year-old neighbour then committed suicide a week later in prison (Daily Mail 16/01/04). A teenager stabbed himself to death in the chest with scissors in front of his helpless father, he thought he was invincible. Then there was the well-publicised case of Luke Mitchell, 16 who slashed and killed his 14 year-old girl friend Jodi Jones in Scotland. He claimed that, over the last year, of the 100 deaths he had dealt with, 10% had a significant link to the drug (Daily Mail 3/11/03). A 22 year-old nurse smoked cannabis for 5 years, became very depressed and hung himself in his bedroom (Daily Mail 12/06/05). A student hung himself after developing a mental illness induced by the use of cannabis. He left a suicide note which read, "Cannabis has ruined my life" (The Times 9/09/03). James Taylor hanged himself in his Torquay flat after smoking cannabis since he was 15. The number of our young patients they would see who have as their priority condition: "Marijuana-induced depression, Marijuana-induced psychosis or Marijuana-induced schizophrenia, would really bring the problem home to them. A possible mechanism for cannabis-induced violence was found in a paper by Howard and Menkes in October 2007. An electrocortical measure of affective impulsivity, Go/No Go contingent negative variation was carried out during and after smoking. Slow brain potentials developed normally in both Go/No Go conditions before and during smoking but were severely disrupted 20 to 30 minutes later ­ peak intoxication! In 2009 Dr Gabriella Gobbi found that teenage cannabis users have decreased serotonin transmission leading to mood disorders, and increased norepinephrine transmission which leads to greater long-term susceptibility to stress. She Said, " Our study is one of the first to focus on the neurobiological mechanisms at the root of this influence of cannabis on depression and anxiety in adolescents. Participants were: individuals with 2 or more discharge diagmnoses of bipolar disorder (n =3743), general population controls (n = 37,429) and unaffected full siblings of individuals with bipolar disorder (n = 4059) 314 individuals with bipolar disorder (8. The risk was mostly confined to patients with substance abuse co-morbidity, and minimal in patients without without substance use comorbidity. This was further attenuated when the unaffected full siblings were used as controls. Data were collected over 5 years from 428 families and their 2 adolescent children in Holland. Daily Mail Tuesday September 28th 2010 reported the case of a public schoolboy, hooked on cannabis, who stabbed his best friend 13 times and left him for dead. The boy, Gavin Doyle, was able to dial 999 and was rescued from woods by a helicopter with heat-seeking equipment. They concluded: the overall association was modest (controlled for sex and age), was statistically robust in 5 countries, and showed no sex difference. The association did not change appreciably with statistical adjustment for mental health problems, except for childhood conduct problems, which reduced the association to nonsignificance.

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Producents - autotrophic organisms, mainly green plants, which is able to create food from inorganic substances; 5. Macroconsuments -heterotrophic organisms, mainly animals, which eat other organisms or organic substances; 6. Microconsuments - heterotrophic organisms, mainly fungi and bacte ria, which destroy and degrade dead organisms, adsorb some products o f degradation and release inorganic and organic substances for fur ther usage by producents. The geographic localization o f main world ecosystems correlates with climate and land zone. The most expressive picture o f ecosystem can be observed on a plane flight from one pole to another. The main world ecosystems are tundra, taiga, temperate de ciduous forest, tropical forest, grassland, desert, mountains, oceans and so on. It is important to note that pathogenic organism, transmitter, and recipients are the parts o f particular ecosystem, such as taiga, grassland and so on. All these parts and relations are presented in centers o f transmissional diseases. Biogeocenosis is limited in territory, internally similar system o f functionally related organisms and nonliving environment, which has particular energy state, type and rate o f substance and information exchange (V. The eco logical influence o f one population extends throughout the biocenosis in all direc tions, but the more chains have been passed, the less intensive influence is. The indexes o f structure and functioning of biocenosis are species composition, number o f trophic levels, primary production, and intension o f substance and energy flow. The most stable is biogeocenoses, which have high species variety, existence o f non-spetializated species, slight separation from neighboring systems and big biomass. It includes all life creatures o f Earth, which interact with physical environment o f Earth. Further development o f concept about biosphere is connected with name of Russian scientists V. He suggested that biosphere contains four main components; living substance - all living 214 organisms; biogenic substance - all substance which is made by living organisms (atmospheric gases, bituminous coal, lime and so on); stagnant substance - is made without organisms (volcano, meteors); biostagnant substance - is result of collaboration of organisms and abiogenic processes (wind, water and so on). The terms "living substance" and "stagnant substance" which were used by him are not very successful. Now following terms are in use: community of organisms, living shell o f earth, life film, and Earth biomass. In spite o f "stagnant substance" the following terms are used: mineral elements, inorganic substance, abiogenic substance. The lower border is limited by organic sedimentations on the oceans bottom (more than 10 kilometers o f depth). It includes all organisms and their rests, parts o f lithosphere, hydrosphere, and atmosphere, which have been changed by living organism and which are the place o f their living now. The rapid industrialization of modern society brought two new terms to ecol ogy: "human ecology" and "ecology of society". Human ecology is defined as a science that studies principles ofenvironment and society interactions and methods o f conservancy. The subject of human ecology is studying o f principles o f environment and society interactions, principles o f population growth, health care, and improvement of physical and psychical abilities o f Homo sapiens. It gives possibilities to study general, fundamental principles o f preserving health in all human populations, concerning all climates, geographical, social and industrial conditions. Human ecology studies the principles o f existing and development of anthropoecologycal systems, which are communities o f people having dynamic exchange with environment to satisfy the requirements. The communities o f people differ from each other by social structure and industry development. In anthropoecological system, the relationships between humans and nature can be o f two types. At first, there are changes in biological and social indexes o f an individual and a whole society, directed to adopt the natural conditions. The general result of interactions in anthropoecological sys tems is individual and group adoption o f humans to live in different environments, with different natural, industrial and cultural conditions. Human receives a full adoption, including physical, emotional, ecological, and industrial. Agrocenosis (from Greek "agros" - field) is a community of organisms that inhabit agricultural territories.

References:

  • https://medicine.yale.edu/intmed/drc/diabetescenter/living/50135_Yale%20National%20F_102165_284_13584_v1.pdf
  • http://www.brainm.com/software/pubs/brain/Hnbk%20of%20Medical%20Neuropsychology.pdf
  • https://cintabukumedis.files.wordpress.com/2014/01/intravenous-medication.pdf
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