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Background: Atypical hemolytic uremic syndrome (aHUS) can be associated with mutations, deletions, or hybrid genes in factor H-related (FHR) proteins. Methods: A child with aHUS was investigated. Genetics was assessed by Sanger and next generation sequencing. Serum FHR5 was evaluated by immunoblotting, ELISA, and by induction of rabbit red blood cell hemolysis in the presence/absence of recombinant human rFHR5. Mutagenesis was performed in HEK cells. Results: A heterozygous genetic variant in factor H-related protein 5 (CFHR5), M514R, was found in the child, who also had a homozygous deletion of CFHR3/CFHR1, and antibodies to factor H, as well as low levels of C3. Patient serum exhibited low levels of FHR5. In the presence of rabbit red blood cells, patient serum induced hemolysis which decreased when rFHR5 was added at physiological concentrations. Similar results were obtained using serum from the father, bearing the CFHR5 variant without factor H antibodies. Patient FHR5 formed normal dimers. The CFHR5 M514R variant was expressed in HEK cells and minimal secretion was detected whereas the protein level was elevated in cell lysates. Conclusions: Decreased secretion of the product of the mutant allele could explain the low FHR5 levels in patient serum. Reduced hemolysis when rFHR5 was added to serum suggests a regulatory role regarding complement activation on red blood cells. As such, low levels of FHR5, as demonstrated in the patient, may contribute to complement activation. [ABSTRACT FROM AUTHOR]

Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, although down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci; the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses were found robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who generate and share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers' use of the summary statistics. [ABSTRACT FROM AUTHOR]

This study explores features of food system transformations towards sustainability in the Farm to Fork Strategy in relation to perspectives of Swedish food system practitioners. Transformations towards sustainable food systems are essential to achieve the United Nations' 2030 Agenda and the need for more sustainable food systems has been recognised in the European Green Deal and its Farm to Fork Strategy. The Swedish ambition to act as a global leader in achieving the 2030 Agenda and the European Commission's aspiration for Europe to lead global food system transformations offer a critical opportunity to study transformational processes and agents of change in a high-income region with externalised environmental and sustainability impacts. Drawing on theories of complex systems transformations, this study identifies features of food system transformations, exploring places to intervene and examines the roles, responsibilities, and agency related to these changes. The results of this study provide three main conclusions highlighting (i) alignment of high-level policy and the perspectives of national practitioners at the paradigm level, especially concerning how food is valued, which is a crucial first step for transformational processes to come about (ii) a lack of clarity as well as diversity of pathways to transform food systems although common objectives are expressed, and (iii) governance mechanisms as enablers for a diversity of transformations. Moreover, these processes must acknowledge the contextual and complex nature of food systems and the level of agency and power of actors. [ABSTRACT FROM AUTHOR]

While increasing hopes are being attached to deliberate societal transformative change to achieve the targets of the 2030 Agenda and the Paris Agreement, questions remain about whether and whereby such profound systemic change can be governed. This paper analyses how transformative changes are intended to be encouraged and achieved, where and when. The paper explores critical drivers and how they relate to leverage points at different places in the societal systems. The paper builds on a comprehensive sense-making analysis of scholarly literature, policy documents, including countries' contributions to the Paris Agreement and national reviews of progress towards the UN Sustainable Development Goals, international news media and lay focus group discussions on five continents. There are great variations in how drivers were made sense of in the data. The many ongoing interacting transformations across societies involve different social, cultural, and political contexts, while the implementation of the 2030 Agenda also contains goal conflicts and unavoidable trade-offs. The paper highlights four categories of drivers as particularly important to consider in view of international transformation efforts: technological innovations, political economy redistribution, new narratives, and transformative learning. Four features are important for bringing clarity on how deliberate transformations can be encouraged: (1) the function of drivers in enabling and restricting transformations of societal systems characterised by detailed or dynamic complexity, (2) cultural and geographical contexts of transformations, (3) where in the systems the drivers are intended to intervene, and (4) the role of critical junctions in time, where transformative trajectories can branch out. [ABSTRACT FROM AUTHOR]

Introduction: The serotonin 5-HT4 receptor agonist prucalopride is approved in the European Union for the treatment of chronic constipation. This offered the unique opportunity to include real-world observational data on cardiovascular safety in the new drug application for approval of prucalopride in the USA.Methods: This observational population-based cohort study (EUPAS9200) conducted in five data sources (three in the UK, one in Sweden, and one in Germany [which was subsequently excluded from the pooled analyses]) aimed to estimate the pooled adjusted incidence rate ratio for major adverse cardiovascular events (defined as hospitalization for non-fatal acute myocardial infarction or stroke, and in-hospital cardiovascular death) in adult initiators of prucalopride compared with initiators of polyethylene glycol 3350 (PEG) following a common protocol. Standardized incidence rates and incidence rate ratios of major adverse cardiovascular events were derived using propensity score stratification. Sensitivity analyses explored the impact of exposure definition, outcome categories, interim cancer, and unmeasured confounding.Results: The pooled analyses included 5715 initiators of prucalopride and 29,372 initiators of PEG. Average duration of use was 175 days for prucalopride and 82 days for PEG. The pooled standardized incidence rate per 1000 person-years (95% confidence interval) of major adverse cardiovascular events was 6.57 (3.90-10.39) for patients initiating prucalopride and 10.24 (6.97-14.13) for PEG. The pooled adjusted incidence rate ratio for major adverse cardiovascular events was 0.64 (95% confidence interval 0.36-1.14). Results remained consistent in various sensitivity analyses.Conclusions: The pooled incidence rate ratio estimate was consistent with no indication of an increased risk above the pre-specified safety threshold of 3.00 for major adverse cardiovascular events in patients with chronic constipation using prucalopride as compared with PEG. [ABSTRACT FROM AUTHOR]

Introduction: Given prior safety experience with other 5-HT4 agonists for chronic constipation, an observational, population-based cohort study in five data sources from Germany, Sweden, and the UK was conducted to evaluate the cardiovascular safety of prucalopride.Objectives: Our objective is to describe the methods and resulting comparability of cohorts in a multi-database, multinational study of prucalopride initiators and polyethylene glycol 3350 (PEG) initiators following a harmonized protocol.Methods: Prucalopride initiators were matched on age, sex, and index date to PEG initiators (1:5 ratio). Study exposures, cardiovascular risk factors, and other covariates were identified from healthcare utilization codes harmonized across databases. Cardiovascular outcomes were identified using database-specific algorithms based on diagnosis codes. The propensity score (PS) in each database was estimated using logistic regression, with prucalopride versus PEG as the outcome and including clinically relevant variables associated with major adverse cardiovascular events.Results: In total, 12,030 prucalopride initiators and 59,985 PEG initiators were identified. After matching and trimming, cohorts from the UK and Sweden were well-balanced for cardiovascular risk factors and cancer. However, in Germany, PEG initiators remained older and sicker than prucalopride initiators. The prevalence of these characteristics also differed from those in the UK and Sweden. The pooled analyses included only data from the UK and Sweden.Conclusions: Matching, trimming, and PS stratification yielded comparable cohorts in four of five data sources. Use of these methods could not achieve balance for key covariates within the German cohort, likely due to reimbursement differences in Germany. [ABSTRACT FROM AUTHOR]

This paper critiques the so-called "Green Revolution" as a political myth of averted famine. A "political myth," among other functions, reflects a narrative structure that characterizes understandings of causality between policy action and outcome. As such, the details of a particular political myth elevate certain policy options (and families of policy options) over others. One important narrative strand of the political myths of the Green Revolution is a story of averted famine: in the 1950s and 1960s, scientists predicted a global crisis to emerge in the 1970s and beyond, created by a rapidly growing global population that would cause global famine as food supplies would not keep up with demand. The narrative posits that an intense period of technological innovation in agricultural productivity led to increasing crop yields which led to more food being produced, and the predicted crisis thus being averted. The fact that the world did not experience a global famine in the 1970s is cited as evidence in support of the narrative. Political myths need not necessarily be supported by evidence, but to the extent that they shape understandings of cause and effect in policymaking, political myths which are not grounded in evidence risk misleading policymakers and the public. We argue a political myth of the Green Revolution focused on averted famine is not well grounded in evidence and thus has potential to mislead to the extent it guides thinking and action related to technological innovation. We recommend an alternative narrative: The Green Evolution, in which sustainable improvements in agricultural productivity did not necessarily avert a global famine, but nonetheless profoundly shaped the modern world. More broadly, we argue that one of the key functions of the practice of technology assessment is to critique and to help create the political myths that preserve an evidence-grounded basis for connecting the cause and effect of policy action and practical outcomes. [ABSTRACT FROM AUTHOR]

This essay discusses the concept of usefulness of research for climate change adaptation. Based on prior research and stakeholder interactions with policymakers and practitioners in the Nordic countries, we contend that critical issues related to the usefulness of adaptation research seem less associated with content (i.e. research outputs), but rather centre around the efforts made to design and communicate research, that is, to put research at the service of society and make the case for adaptation on the political agenda. This, we argue, to some extent mirrors the situation and political context in the Nordic countries, where adaptation in many locations still is an issue in its infancy, not firmly established on the political agendas, and where working procedures are not yet institutionally settled. In this context, science is considered and sometimes used as a discursive tool to make the case for adaptation. Based on the calls for research that inspires, raises hope and helps to raise the issue of adaptation on the political agendas, we elaborate the role of honest issue advocates for researchers in the field of adaptation science. [ABSTRACT FROM AUTHOR]

Least developed countries often lack the requisite capacity to implement climate change adaptation projects. The Least Developed Countries Fund (LDCF) is a scheme where industrialized countries have (as of early 2016) disbursed $934.5 million in voluntary contributions, raised more than four times that amount in co-financing, and supported 213 adaptation projects across 51 least developed countries. But what sorts of challenges have arisen during implementation? Based on extensive field research in five least developed countries-Bangladesh, Bhutan, Cambodia, the Maldives, and Vanuatu-and original data collected from almost 150 research interviews, this article qualitatively explores both the benefits and challenges of LDCF projects in the Asia-Pacific. It finds that while LDCF projects do contribute to enhancing multiple types of infrastructural, institutional, and community-based adaptive capacity, they also suffer from uncertainty, a convoluted management structure, and an inability to fully respond to climate risks. Based on these findings, the study concludes that adaptation must be pursued as a multidimensional process; and that LDCF activities have tended to promote marginal rather than more radical or systematic transformations. [ABSTRACT FROM AUTHOR]

Globalization processes have rendered non-state actors an integral part of global governance. The body of literature that has examined non-state actor involvement in global governance has focused mainly on whether and how non-state actors can influence states. Less attention has been paid to the comparative advantages of non-state actors to answer questions about agency across categories of non-state actors, and more precisely what governance activities non-state actors are perceived to fulfil. Using unique survey material from two climate change conferences, we propose that different categories of non-state actors have distinct governance profiles. We further suggest that the different governance profiles are derived from particular power sources and that agency is a function of these profiles. The study thereby contributes to a strand in the literature focusing on the authority of non-state actors in climate governance and broadens the methodological toolkit for studying the 'governors' of global governance. [ABSTRACT FROM AUTHOR]

When do states allow nonstate actors (NSAs) to observe negotiations at intergovernmental meetings? Previous studies have identified the need for states to close negotiations when the issues under discussion are sensitive. This paper argues that sensitivity alone cannot adequately explain the dynamic of closing down negotiations to observers. Questions that have received little attention in the literature include which issues are considered sensitive and how the decision is made to move the negotiations behind closed doors. This paper examines the practices of NSA involvement in climate diplomacy from three analytical perspectives: functional efficiency, political dynamics, and historical institutionalism. Based on interviews and UNFCCC documents, this paper suggests that to understand the issue of openness in negotiations, institutional factors and the politics of NSA involvement need to be better scrutinized. The paper shows that each perspective has particular advantages when analyzing different dimensions of the negotiations, with implications of how we understand the role of NSAs in global environmental governance. [ABSTRACT FROM AUTHOR]

In a global context, the outlook for the Nordic region is relatively favourable, given its relatively stronger resiliency to climate change impacts in comparison to many other geo-political regions of the world. Overall, the projected climatic changes include increases in mean temperatures and in precipitation, although regional variations can be significant. The countries' robust institutions and economies give them a strong capacity to adapt to these changes. Still, the need for adaptation to the changing climate has been and still is substantial, and in most of the region, there has been progress on the issue. This paper explores the potential for Nordic cooperation on adaptation; specifically, for the development of a regional adaptation strategy. In particular, it addresses two questions (1) What is the current state of adaptation in the Nordic countries? and (2) What are the potential benefits and weaknesses of a Nordic strategy for adaptation? In order to answer these two questions, this paper examines reviews the current national adaptation policies of each Nordic country and discusses the challenges facing a Nordic strategy and finally assesses the potential for common Nordic adaptation policy and further cooperation. [ABSTRACT FROM AUTHOR]

This article examines key issues in operationalizing a registry of nationally appropriate mitigation actions (NAMAs) undertaken by developing countries party to the United Nations framework convention on climate change. It analyzes goals, outcomes, and institutional prerequisites underlying various proposals to determine how a NAMA mechanism could work in international climate cooperation. The different proposals for how NAMA shall be designed relate to three basic effort-sharing arrangements in a future climate regime: binding commitments for all Parties, purely voluntary commitments for all, and legally binding commitments for Annex I countries but voluntary ones for others. We conclude that a NAMA registry could be designed so as initially to suit all three types of effort-sharing regimes. The article identifies three areas of potential common ground in a registry irrespective of effort-sharing type: the principle of common but differentiated responsibilities, the sustainable development objectives of the Convention, and the need for a systemic transition toward low-carbon energy technologies. [ABSTRACT FROM AUTHOR]

Mistra's Climate Policy Research Program, Clipore, is one of the largest research programs directed to support international climate policy development, involving research groups in Sweden, Norway, United States and India. It has been running from 2004 to 2011 with a budget of more than 100 MSEK (15 M USD). The paper briefly describes the program and its outcomes in relation to climate policy development. Discussion focuses on how the program has been able to be in the front of and include the development of emissions trading systems in Europe and the United States and how the program has been able to follow and produce inputs to the agenda of the United Nations Framework Convention on Climate Change (UNFCCC). The paper also discusses how the program has managed to present its outcomes and maintain an active dialogue with the various stakeholders. The paper emphasises options and obstacles in the communication between science and policy. [ABSTRACT FROM AUTHOR]

Leadership is an essential ingredient in reaching international agreements and overcoming the collective action problems associated with responding to climate change. In this study, we aim at answering two questions that are crucial for understanding the legitimacy of leadership in international climate change negotiations. Based on the responses of three consecutive surveys distributed at COPs 14-16, we seek first to chart which actors are actually recognized as leaders by climate change negotiation participants. Second, we aim to explain what motivates COP participants to support different actors as leaders. Both these questions are indeed crucial for understanding the role, importance, and legitimacy of leadership in the international climate change regime. Our results show that the leadership landscape in this issue area is fragmented, with no one clear-cut leader, and strongly suggest that it is imperative for any actor seeking recognition as climate change leader to be perceived as being devoted to promoting the common good. [ABSTRACT FROM AUTHOR]

In this work we analyse a method to construct numerically efficient and computationally cheap sparse approximations of some of the matrix blocks arising in the block-factorized preconditioners for matrices with a two-by-two block structure. The matrices arise from finite element discretizations of partial differential equations. We consider scalar elliptic problems, however the approach is appropriate also for other types of problems such as parabolic problems or systems of equations. The technique is applicable for both selfadjoint and non-selfadjoint problems, in two as well as in three space dimensions. We analyse in detail the two-dimensional case and provide extensive numerical evidence for the efficiency of the proposed matrix approximations, both serial and parallel. Two- and three-dimensional tests are included. [ABSTRACT FROM AUTHOR]

Summary. Present pharmacotherapy of major depression is, in principle, based on enhancement of central monoaminergic neurotransmission. Clinical studies utilizing depletion experiments indicate that antidepressants which primarily enhance serotonergic or noradrenergic central activity, i.e. serotonin or nor-adrenaline reuptake inhibitors, largely work by two separate neuronal pathways. However, experimental studies have shown that noradrenaline may regulate serotonergic neurotransmission both at the serotonin cell body and nerve-terminal level. We therefore investigated the effects of the selective NRI reboxetine on serotonergic neuronal activity and extracellular levels of transmitter in the nerve-terminal area. In vivo electrophysiological experiments showed that low doses of reboxetine significantly enhance the firing rate of serotonergic neurons in the dorsal raphe nucleus of anaesthetized rats. Also, in the medial prefrontal cortex reboxetine (3 mg/kg s.c.) enhanced, whereas citalopram (3 mg/kg s.c.) reduced, extracellular concentrations of serotonin measured by means of microdialysis in awake rats, using a low dose of citalopram (0,5 µM) in the perfusion solution. Local administration of reboxetine only induced an increase in cortical serotonin levels at very high concentrations (1000 µM). Hence, NRIs may cause a secondary enhancement of central serotonergic activity by a mechanism separate from 5-HT reuptake inhibition; an effect that may contribute to their clinical antidepressant efficacy. [ABSTRACT FROM AUTHOR]

We have previously observed that addition of an α2-adrenoceptor antagonist to a selective dopamine (DA) D2 receptor antagonist enhances the antipsychotic-like effect of the D2 blocker and also selectively increases DA output in the medial prefrontal cortex (mPFC) in rats. These data also correlate well with previous clinical trials showing augmentation by an equivalent drug combination in schizophrenia. Since the selective noradrenaline reuptake inhibitor reboxetine was found to cause similar effects on the mesolimbocortical DA system as α2-adrenoceptor antagonists, the present study was undertaken to explore whether also reboxetine might augment the effect of the DA D2 receptor antagonist raclopride in the same preclinical model of antipsychotic activity, the conditioned avoidance response (CAR) test. We also investigated the effect of this combination in the catalepsy test for extrapyramidal side effect liability, as well as on DA output in the mPFC and the nucleus accumbens, respectively. Reboxetine (6 mg/kg, i.p.) significantly enhanced the suppressant effect of raclopride (0.1 mg/kg, s.c.) on CAR without affecting catalepsy. Administration of raclopride (0.1 mg/kg, s.c.) to rats pretreated with reboxetine (6 mg/kg, i.p.) resulted in a greatly enhanced effect on DA output in the mPFC but not in the nucleus accumbens when compared with raclopride alone. Consequently, these results suggest that noradrenaline reuptake inhibition may provide means of augmenting the efficacy of classical D2-antagonists in the treatment of schizophrenia, and, in principle, to generate an atypical antipsychotic drug profile. [Copyright &y& Elsevier]

In vivo microdialysis was used to investigate the effects of acute injections of harmine on extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxindoleacetic acid (5-HIAA) in the striatum of awake rats. Administration of harmine in doses of 0.5, 2.5, and 10 mg/kg (i.p.) elicited a dose-dependent increase of the dopamine efflux to 152, 173, and 243% and a decrease in DOPAC to 52, 36, and 10%, and HVA to 67, 45, and 20% throughout, respectively; 5-HIAA concentrations were decreased to 81, 74, and 72% only. In contrast to D-amphetamine, which also increases dopamine release and decreases its metabolites, the stimulatory action of harmine on dopamine release in the striatum was totally abolished in the presence of tetrodotoxin (1 µM). Similar to monoamine oxidase (MAO)-A inhibitors, harmine potentiated the stimulatory effect of D-amphetamine (10 µM), infused by reverse microdialysis in the striatum, on dopamine release. Pre-treatment with the benzodiazepine receptor antagonist flumazenil (5 mg/kg, i.p.) did not modulate the effect of harmine on striatal dopamine release and metabolism. Administration of the reversible MAO-A inhibitor, moclobemide (20 mg/kg, i.p.), induced an increase in dopamine to 256% and a decrease in DOPAC, HVA, and 5-HIAA to 30, 24, and 62%, respectively, reproducing a pattern similar to that of harmine. Taken together, these results indicate that harmine affects the brain dopamine system probably by acting as a MAO-A inhibitor and not as an inverse agonist for the benzodiazepine receptors. [ABSTRACT FROM AUTHOR]

The effect on growth of distributing feed over a few hours compared tomore frequent meals was tested on 1+ Arctic charr ( Salvelinus alpinus L.) and 1+ rainbow trout ( Oncorhynchus mykiss Walbaum). Triplicate hatchery groups for each treatment were fed at a ration level of 1%/dayeither with few meals (8 times per day divided into morning and evening)or with frequent meals (32 meals equally distributed during the day). Wefound an opposite effect of meal frequency on growth in the two species.Low feeding intensity (8 meals per day) had a significantly positive effecton growth in rainbow trout but a significantly negative effect on growth inArctic charr when compared to feeding the fish frequent meals. Theopposite response to meal frequency is likely to be an effect of thedifferences in activity during feeding. Rainbow trout feed much moreaggressively than charr which can result in feeding being a more stressfulevent. In this experiment, the specific growth rate was lower and the feedconversion ratio higher for Arctic charr compared to rainbow trout. [ABSTRACT FROM AUTHOR]

The effects of time restricted feeding, possibility of bottomfeeding and stocking density on the growth of Arctic charr( Salvelinus alpinus L.) were examined in fish held at lowtemperature (<2 °C). Fish fed for a restricted time (1 h) hadsignificantly (p < 0.05) lower specific growth rate (0.15 vs0.32% per day) than those fed the same ration over an extendedtime period (12 h). Increasing stocking densities had a positive andsignificant effect (p < 0.05) on growth with SGR increasing from 0.27to 0.52% per day at 2–30 kg m-3. Fish withaccess to feed on the tank floor had a significantly higher (p <0.05) growth rate (0.3 vs 0.13% per day) than those without thepossibility to feed from the bottom. When fish were held underconditions without access to the bottom a doubling of the feed rationdid not result in a significant (p > 0.05) increase in growth rate(0.13 vs 0.12%percnt; per day). [ABSTRACT FROM AUTHOR]

Abstract Rationale: Pindolol has been reported to shorten the onset of antidepressant action of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) as well as to increase their efficacy. It has been postulated that pindolol enhances the antidepressant effect of SSRIs by blocking somatodendritic 5-HT[sub 1A] autoreceptors, thus antagonizing the SSRI-induced feedback inhibition of midbrain 5-HT cell firing. A recent study, however, found that pindolol suppresses the firing rate of central 5-HT cells, suggesting that the compound possesses agonistic activity at 5-HT[sub 1A] autoreceptors. Objectives: The purpose of the present study was to investigate if acute administration of (-)pindolol antagonizes the decrease in firing rate of dorsal raphe 5-HT cells produced by acute treatment with the SSRI citalopram. Methods: Extracellular recordings of single 5-HT neurons in the dorsal raphe nucleus in anaesthetized rats. Results: Administration of 0.25 or 3.0 mg/kg (IV) (-)pindolol alone decreased the firing rate of a majority of the 5-HT cells studied, an effect that was reversed by the 5-HT[sub 1A] receptor antagonist WAY100635 (0.1 mg/kg, IV). Neither 0.25 nor 3.0 mg/kg (-)pindolol reversed the citalopram (0.1-0.2 mg/kg, IV)-induced suppression of 5-HT cell activity, but produced a further decrease in firing rate. In contrast, WAY100635 (0.1 mg/kg) completely reversed this effect of citalopram. Yet, pretreatment with 3.0, but not 0.25 mg/kg (-)pindolol significantly attenuated the acute inhibitory effect of citalopram on serotonergic cell firing. Conclusions: The present findings support the previous notion that (-)pindolol possesses prominent agonistic activity at somatodendritic 5-HT[sub 1A] autoreceptors, but also indicate that... [ABSTRACT FROM AUTHOR]

The authors discuss the role of the political economy in adapting to climatic change and global warming. Topics discussed include environmental projects under the Adaptation Fund of the United Nations Framework Convention on Climate Change (UNFCCC), the entrenchment process for climate adaptation projects, and two case studies related to enclosure in the ecosystems of Australia and Norway.

The flow in the negative direction of the gradient vector field associated with the functional total squared (geodesic) curvature ∫ k ds is the so-called curvestraightening flow. This paper will consider spaces of closed curves in closed Euclidean submanifolds. It will define these spaces of curves as submanifolds of certain Hilbert manifolds representing all curves. The main result will then be to show the existence of a particular set of functionals defined on the entire Hilbert manifold which have the following four properties: 1. The directional derivatives of these functionals may be computed by solving an initial value problem for a system of ordinary differential equations. 2. By introducing a suitable Hilbert space basis for the Sobolev spaces used, the gradients may be effectively computed (but of course not explicitly computed, except in very special cases). 3. The gradients span the space normal to the tangent space of the space of closed curves. 4. Despite the fact that these gradients in general are not given explicitly it is nevertheless possible to compute the projection onto the tangent space to the space of closed curves. In particular we do this for the gradient of ∫ k ds. When all details are worked out this gives us an algorithm (which we supply) for finding critical points in the space of closed curves. It is not known if the trajectories actually always converge to critical points. If the functional is modified to include a multiple of the length so the functional becomes ∫ k+λ ds then the above convergence is known for λ>0. The motivating application for the curvestraightening flow is the possibility of using it to find (non-trivial) closed (periodic) geodesics. Note that if λ=0 then a closed geodesic is a global minimum. For any λ, geodesics are critical but there are also other critical points, the so-called elastic curves. The paper concludes by deriving the second variation formula for ∫ k+λ ds along closed geodesics. The quadratic functional associated with the second derivative is shown to be positive definite even for non-zero λ along some closed geodesics in some particular manifolds of interest. [ABSTRACT FROM AUTHOR]

Copyright of Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigate possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1169 controls; 1067 cases) with deeply phenotyped SZ patients. We find strong genetic dependence between EA and SZ that cannot be explained by chance, linkage disequilibrium, or assortative mating. Instead, several genes seem to have pleiotropic effects on EA and SZ, but without a clear pattern of sign concordance. Using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ. Our results reveal that current SZ diagnoses aggregate over at least two disease subtypes: one part resembles high intelligence and bipolar disorder (BIP), while the other part is a cognitive disorder that is independent of BIP. Educational attainment and schizophrenia have a negative phenotypic relationship but show positive genetic correlation. Here, the authors study genetic dependence between the two traits and find that multiple genes have pleiotropic effects on both without a systematic pattern of sign concordance. [ABSTRACT FROM AUTHOR]

The article discusses research in Sweden concerning the use of anticholinergic drugs in the treatment of urinary urge incontinence. The discussion focuses on the adherence rate to continuous treatment or number of refills within a time period for the originator drugs, oxybutynin, any anticholinergic, and warfarin. The study found age was correlated with the patients' adherence to treatment and gender did not affect persistence of drug use.

Copyright of Experientia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)