A comparative analysis of parodic narratives in Thomas Pynchon's the Crying of lot 49 and Svetislav Basara's Fama o biciklistima ; Сравнительный анализ пародийных нарративов в романах Выкрикивается лот 49 Томаса Пинчона и Сказание о велосипедистах Светислава Басары

Rad se bavi komparativnim tumačenjem dela tipskih predstavnika severnoameričke i srpske postmoderne književnosti kroz poređenje parodijskih narativa u romanima Objava broja 49 Tomasa Pinčona i Fama o biciklistima Svetislava Basare. Ispituju se ključni fenomeni vezani za postmoderni roman u kontekstu parodijskih narativa, sa posebnim osvrtom na strukturalne i funkcionalne odlike parodije u postmodernističkoj prozi i polemičku oštricu parodije. Analizira se prisustvo „prethodnih“ tekstova u postmodernom romanu, koje postmoderni roman inkorporira parodirajući ih u jednom novom, savremenom kulturnom i književnom kontekstu. Na taj način, parodija deluje subverzivno i proizvodi društveni komentar, a dela kao što su Objava broja 49 i Fama o biciklistima se mogu posmatrati kao društveno i kritički relevantna. U tom smislu, proučava se politička dimenzija parodijskog književnog teksta, kao i društveni procesi koji su, između ostalog, doveli i do kritičkog parodijskog izraza u modernoj i postmodernoj književnosti. Kroz prizmu dva romana istražuje se na koji način su tehnološki, civilizacijski i kulturni napredak globalizovanog sveta doveli do problema neautentičnosti doživljaja stvarnosti i jezičkog iskazivanja tog doživljaja, zbog kojeg je i parodija postala jedna od diskurzivnih strategija za kojima se poseže. Rad ispituje i metaprozu i intertekstualnost u parodijskom narativu, polazeći od viđenja parodije kao metaproznog, samorefleksivnog teksta koji ne pretenduje na mimetičko predstavljanje stvarnosti, već, kao nezavisna kreativna formacija, u isto vreme aludira na izvore iz kojih proizilazi. Parodija se vidi kao jedna od strategija borbe protiv diskursa moći koji nisu tu da predstave stvarnost, već da je kreiraju. Kroz primere iz Objave broja 49 i Fame o biciklistima rad ispituje na koji način se metaprozni tekst samokomentariše, problematizujući ustaljene prozne konvencije, kao i vremenski trenutak u kom je nastalo kako delo koje je predmet parodije, tako i sama parodija. Rad se takođe bavi (ne)prisustvom lirsko melanholičnog izraza u postmodernom proznom jeziku kao svojevrsnim kontra-narativom parodije, jednom vrstom tuge za izgubljenim jezikom i nostalgije za izgubljenim kontekstom u kome su diskursi koji su herojski, kurtoazni, visoko formalni, itd., mogli da postoje neparodirani, i autentični.The dissertation considers parody as a part of the North-American and Serbian postmodern novelist tradition by comparing the parodic narratives in Thomas Pynchon’s The Crying of Lot 49 and Svetislav Basara’s Fama o biciklistima. The dissertation examines the key phenomena related to parody in the postmodern novel, with a special emphasis on the structural and functional features of parodic language as well as its functional purpose of criticism. It analyzes the parodic presence of precursor texts in the narratives of the two novels, parodied in a new, contemporary cultural and literary context. In this way, parody provides subversive and critical commentary, and the works of fiction such as The Crying of Lot 49 and Fama o biciklistima can be seen as socially and critically relevant. In this sense, the political aspects of the postmodern literary parody are studied, as well as the social processes which led to the formation of critical parodic language in modern and postmodern literature. Through the prism of the two novels, the dissertation investigates the ways in which the technological, cultural and material development in globalized societies resulted in the problem of inauthentic perception of reality and its verbalization, which are the reasons why parody, with its ability to revive old texts in a new context, became one of the chief discursive strategies used in postmodern literature. The dissertation further examines metafictive devices and intertextuality as essential constituents of the parodic narrative, starting from the definition of parody as a metafictive, self-referential text that does not strive for a mimetic representation of reality, but, as an independent creative formation, alludes to the sources that are built into its structure. Parody is seen as a fighting strategy against the discourses of power that do not represent reality, but create it. The interpretations of the excerpts from The Crying of Lot 49 and Fama o biciklistima provide an insight into the ways in which a parodic metafictive text comments on itself, questions literary conventions, the historical period in which the parodied text was created as well as the present moment. The dissertation also deals with the presence of lyrical and melancholic language in the postmodern prose narratives as parody’s special kind of counter-narrative, a linguistic formulation of sorrow for the lost language, and nostalgia for the lost context in which heroic, courteous, romantic, highly formal etc. discourse could have their authentic existence, outside of parody

Experience with developing antibiotic stewardship programmes in Serbia : potential model for other Balkan countries?

Introduction: Antimicrobial resistance (AMR) and inappropriate use of antibiotics in children are important issues. Consequently, there is a need to develop comprehensive stewardship programmes even in hospitals with limited resources starting with children’s hospitals. Method: Retrospective observational analysis of antimicrobial utilization and resistance patterns over five years in a tertiary care children’s hospital in Serbia. Results: Cumulative AMR decreased but were still high, with high cumulative resistance rates among the most widely used antibiotics in the hospital. Total antibiotic use decreased from 2010 to 2014 although there was still high prescribing of reserved antibiotics. Conclusion: Concerns with inappropriate use, and high resistance rates, among some antibiotics used in the hospital are being used to develop guidance on future antibiotic use in this hospital, building on the recently introduced antibiotic stewardship programme, as well as encourage other hospitals in Serbia to review their policies

Climate change adaptation and cross-sectoral policy coherence in southern Africa

To be effective, climate change adaptation needs to be mainstreamed across multiple sectors and greater policy coherence is essential. Using the cases of Malawi, Tanzania and Zambia, this paper investigates the extent of coherence in national policies across the water and agriculture sectors and to climate change adaptation goals outlined in national development plans. A two-pronged qualitative approach is applied using Qualitative Document Analysis of relevant policies and plans, combined with expert interviews from non-government actors in each country. Findings show that sector policies have differing degrees of coherence on climate change adaptation, currently being strongest in Zambia and weakest in Tanzania. We also identify that sectoral policies remain more coherent in addressing immediate-term disaster management issues of floods and droughts rather than longer-term strategies for climate adaptation. Coherence between sector and climate policies and strategies is strongest when the latter has been more recently developed. However to date, this has largely been achieved by repackaging of existing sectoral policy statements into climate policies drafted by external consultants to meet international reporting needs and not by the establishment of new connections between national sectoral planning processes. For more effective mainstreaming of climate change adaptation, governments need to actively embrace longer-term cross-sectoral planning through cross-Ministerial structures, such as initiated through Zambia’s Interim Climate Change Secretariat, to foster greater policy coherence and integrated adaptation planning

Africa

Africa is one of the lowest contributors to greenhouse gas emissions causing climate change, yet key development sectors have already experienced widespread losses and damages attributable to human-induced climate change, including biodiversity loss, water shortages, reduced food production, loss of lives and reduced economic growth (high confidence1).// Between 1.5°C and 2°C global warming—assuming localised and incremental adaptation—negative impacts are projected to become widespread and severe with reduced food production, reduced economic growth, increased inequality and poverty, biodiversity loss, increased human morbidity and mortality (high confidence). Limiting global warming to 1.5°C is expected to substantially reduce damages to African economies, agriculture, human health, and ecosystems compared to higher levels of global warming (high confidence).// Exposure and vulnerability to climate change in Africa are multi-dimensional with socioeconomic, political and environmental factors intersecting (very high confidence). Africans are disproportionately employed in climate-exposed sectors: 55–62% of the sub-Saharan workforce is employed in agriculture and 95% of cropland is rainfed. In rural Africa, poor and female-headed households face greater livelihood risks from climate hazards. In urban areas, growing informal settlements without basic services increase the vulnerability of large populations to climate hazards, especially women, children and the elderly. // Adaptation in Africa has multiple benefits, and most assessed adaptation options have medium effectiveness at reducing risks for present-day global warming, but their efficacy at future warming levels is largely unknown (high confidence)./

Dynamic modeling of mean-reverting spreads for statistical arbitrage

Statistical arbitrage strategies, such as pairs trading and its generalizations, rely on the construction of mean-reverting spreads enjoying a certain degree of predictability. Gaussian linear state-space processes have recently been proposed as a model for such spreads under the assumption that the observed process is a noisy realization of some hidden states. Real-time estimation of the unobserved spread process can reveal temporary market inefficiencies which can then be exploited to generate excess returns. Building on previous work, we embrace the state-space framework for modeling spread processes and extend this methodology along three different directions. First, we introduce time-dependency in the model parameters, which allows for quick adaptation to changes in the data generating process. Second, we provide an on-line estimation algorithm that can be constantly run in real-time. Being computationally fast, the algorithm is particularly suitable for building aggressive trading strategies based on high-frequency data and may be used as a monitoring device for mean-reversion. Finally, our framework naturally provides informative uncertainty measures of all the estimated parameters. Experimental results based on Monte Carlo simulations and historical equity data are discussed, including a co-integration relationship involving two exchange-traded funds.Comment: 34 pages, 6 figures. Submitte

A Novel and Selective Dopamine Transporter Inhibitor, (S)-MK-26, Promotes Hippocampal Synaptic Plasticity and Restores Effort-Related Motivational Dysfunctions

Dopamine (DA), the most abundant human brain catecholaminergic neurotransmitter, modulates key behavioral and neurological processes in young and senescent brains, including motricity, sleep, attention, emotion, learning and memory, and social and reward-seeking behaviors. The DA transporter (DAT) regulates transsynaptic DA levels, influencing all these processes. Compounds targeting DAT (e.g., cocaine and amphetamines) were historically used to shape mood and cognition, but these substances typically lead to severe negative side effects (tolerance, abuse, addiction, and dependence). DA/DAT signaling dysfunctions are associated with neuropsychiatric and progressive brain disorders, including Parkinson's and Alzheimer diseases, drug addiction and dementia, resulting in devastating personal and familial concerns and high socioeconomic costs worldwide. The development of low-side-effect, new/selective medicaments with reduced abuse-liability and which ameliorate DA/DAT-related dysfunctions is therefore crucial in the fields of medicine and healthcare. Using the rat as experimental animal model, the present work describes the synthesis and pharmacological profile of (S)-MK-26, a new modafinil analogue with markedly improved potency and selectivity for DAT over parent drug. Ex vivo electrophysiology revealed significantly augmented hippocampal long-term synaptic potentiation upon acute, intraperitoneally delivered (S)-MK-26 treatment, whereas in vivo experiments in the hole-board test showed only lesser effects on reference memory performance in aged rats. However, in effort-related FR5/chow and PROG/chow feeding choice experiments, (S)-MK-26 treatment reversed the depression-like behavior induced by the dopamine-depleting drug tetrabenazine (TBZ) and increased the selection of high-effort alternatives. Moreover, in in vivo microdialysis experiments, (S)-MK-26 significantly increased extracellular DA levels in the prefrontal cortex and in nucleus accumbens core and shell. These studies highlight (S)-MK-26 as a potent enhancer of transsynaptic DA and promoter of synaptic plasticity, with predominant beneficial effects on effort-related behaviors, thus proposing therapeutic potentials for (S)-MK-26 in the treatment of low-effort exertion and motivational dysfunctions characteristic of depression and aging-related disorders

Methods for calculating Protection Equality for conservation planning

Protected Areas (PAs) are a central part of biodiversity conservation strategies around the world. Today, PAs cover c15% of the Earth’s land mass and c3% of the global oceans. These numbers are expected to grow rapidly to meet the Convention on Biological Diversity’s Aichi Biodiversity target 11, which aims to see 17% and 10% of terrestrial and marine biomes protected, respectively, by 2020. This target also requires countries to ensure that PAs protect an “ecologically representative” sample of their biodiversity. At present, there is no clear definition of what desirable ecological representation looks like, or guidelines of how to standardize its assessment as the PA estate grows. We propose a systematic approach to measure ecological representation in PA networks using the Protection Equality (PE) metric, which measures how equally ecological features, such as habitats, within a country’s borders are protected. Extending research in Barr et al. (2011), we present an R package and two Protection Equality (PE) measures; proportional to area PE, and fixed area PE, which measure the representativeness of a country’s PA network. We illustrate the PE metrics with two case studies: coral reef protection across countries and ecoregions in the Coral Triangle, and representation of ecoregions of six of the largest countries in the world. Our results provide repeatable transparency to the issue of representation in PA networks and provide a starting point for further discussion, evaluation and testing of representation metrics. They also highlight clear shortcomings in current PA networks, particularly where they are biased towards certain assemblage types or habitats. Our proposed metrics should be used to report on measuring progress towards the representation component of Aichi Target 11. The PE metrics can be used to measure the representation of any kind of ecological feature including: species, ecoregions, processes or habitats

Behavioral and Dopamine Transporter Binding Properties of the Modafinil Analog (S, S)-CE-158: Reversal of the Motivational Effects of Tetrabenazine and Enhancement of Progressive Ratio Responding

Rationale: Atypical dopamine (DA) transport blockers such as modafinil and its analogs may be useful for treating motivational symptoms of depression and other disorders. Previous research has shown that the DA depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards a low-effort bias in effort-based choice tasks. This is consistent with human studies showing that people with major depression show a bias towards low-effort activities. Objectives: Recent studies demonstrated that the atypical DA transport (DAT) inhibitor (S)-CE-123 reversed tetrabenazine-induced motivational deficits, increased progressive ratio (PROG) lever pressing, and increased extracellular DA in the nucleus accumbens. In the present studies, a recently synthesized modafinil analog, (S, S)-CE-158, was assessed in a series of neurochemical and behavioral studies in rats. Results: (S, S)-CE-158 demonstrated the ability to reverse the effort-related effects of tetrabenazine and increase selection of high-effort PROG lever pressing in rats tested on PROG/chow feeding choice task. (S, S)-CE-158 showed a high selectivity for inhibiting DAT compared with other monoamine transporters, and systemic administration of (S, S)-CE-158 increased extracellular DA in the nucleus accumbens during the behaviorally active time course, which is consistent with the effects of (S)-CE-123 and other DAT inhibitors that enhance high-effort responding. Conclusions: These studies provide an initial neurochemical characterization of a novel atypical DAT inhibitor, and demonstrate that this compound is active in models of effort-related choice. This research could contribute to the development of novel compounds for the treatment of motivational dysfunctions in humans. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.The authors would like to acknowledge Eurofins DiscoverX Corporation (Fremont, CA)

The novel atypical dopamine uptake inhibitor (S)-CE-123 partially reverses the effort-related effects of the dopamine depleting agent tetrabenazine and increases progressive ratio responding

Animal studies of effort-based choice behavior are being used to model effort-related motivational dysfunctions in humans. With these procedures, animals are offered a choice between high-effort instrumental actions leading to highly valued reinforcers vs. low effort/low reward options. Several previous studies have shown that dopamine (DA) uptake inhibitors, including GBR12909, lisdexamfetamine, methylphenidate, and PRX-14040, can reverse the effort-related effects of the vesicular monoamine transport blocker tetrabenazine, which inhibits DA storage. Because many drugs that block DA transport act as major stimulants that also release DA, and produce a number of undesirable side effects, there is a need to develop and characterize novel atypical DA transport inhibitors. (S)-CE-123 ((S)-5-((benzhydrylsulfinyl) methyl) thiazole) is a recently developed analog of modafinil with the biochemical characteristics of an atypical DA transport blocker. The present paper describes the enantioselective synthesis and initial chemical characterization of (S)-CE-123, as well as behavioral experiments involving effort-based choice and microdialysis studies of extracellular DA. Rats were assessed using the fixed ratio 5/chow feeding choice test. Tetrabenazine (1.0 mg/kg) shifted choice behavior, decreasing lever pressing and increasing chow intake. (S)-CE-123 was coadministered at doses ranging from 6.0 to 24.0 mg/kg, and the highest dose partially but significantly reversed the effects of tetrabenazine, although this dose had no effect on fixed ratio responding when administered alone. Additional experiments showed that (S)-CE-123 significantly increased lever pressing on a progressive ratio/chow feeding choice task and that the effective dose (24.0 mg/kg) increased extracellular DA in nucleus accumbens core. In summary, (S)-CE-123 has the behavioral and neurochemical profile of a compound that can block DA transport, reverse the effort-related effects of tetrabenazine, and increase selection of high-effort progressive ratio responding. This suggests that (S)-CE-123 or a similar compound could be useful as a treatment for effort-related motivational dysfunction in humans

Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers

<p>Abstract</p> <p>Background</p> <p>There has been an increase in 'risk sharing' schemes for pharmaceuticals between healthcare institutions and pharmaceutical companies in Europe in recent years as an additional approach to provide continued comprehensive and equitable healthcare. There is though confusion surrounding the terminology as well as concerns with existing schemes.</p> <p>Methods</p> <p>Aliterature review was undertaken to identify existing schemes supplemented with additional internal documents or web-based references known to the authors. This was combined with the extensive knowledge of health authority personnel from 14 different countries and locations involved with these schemes.</p> <p>Results and discussion</p> <p>A large number of 'risk sharing' schemes with pharmaceuticals are in existence incorporating both financial-based models and performance-based/outcomes-based models. In view of this, a new logical definition is proposed. This is "<it>risk sharing' schemes should be considered as agreements concluded by payers and pharmaceutical companies to diminish the impact on payers' budgets for new and existing schemes brought about by uncertainty and/or the need to work within finite budgets</it>". There are a number of concerns with existing schemes. These include potentially high administration costs, lack of transparency, conflicts of interest, and whether health authorities will end up funding an appreciable proportion of a new drug's development costs. In addition, there is a paucity of published evaluations of existing schemes with pharmaceuticals.</p> <p>Conclusion</p> <p>We believe there are only a limited number of situations where 'risk sharing' schemes should be considered as well as factors that should be considered by payers in advance of implementation. This includes their objective, appropriateness, the availability of competent staff to fully evaluate proposed schemes as well as access to IT support. This also includes whether systematic evaluations have been built into proposed schemes.</p