A world environmental organization?

We evaluate possibilities for a new World Environmental Organization (WEO), with our discussion motivated both by recent calls for such an organization in light of WTO trade and environment conflicts and the relative absence of internalization of global externalities. We propose an organization building upon the idea of facilitating Coasian deals on the global environment. This contrasts to attempts to agree on a statement of global principles, as in the Rio declaration and Agenda 21 as the main vehicle for global environmental improvements. To motivate the establishment of such an organization, we itemize the ways in which global environmental deals are presently restrained by various impediments, including free riding, property right ambiguities, and mechanisms for authentification and verification. We indicate how such a WEO might help in each of these areas, stressing the differences from the WTO which is a much narrower bargaining framework. We conclude with a discussion of why the developing countries might or might not be interested in such a proposal, and emphasize their potential both to secure significant resource transfers in exchange for environmental concessions, and to cooperate in bargaining with the WEO as a focal point and secure sharply better terms. We note, however, both their broad systemic concerns over another global agency which they fear might be used to pressure them, and what some countries see as the inability of such an entity to deal with their central concerns in the area; namely ameliorating internal environmental problems via transfer of technology. We conclude by arguing that a WEO can offer joint benefits; raising environmental quality for those willing to pay for it, and acting as a vehicle for securing transfers of resources in return for environmental commitments

Carbon Motivated Border Tax Adjustments: Old Wine in Green Bottles?

We discuss emerging proposals for border tax adjustments (BTAs) to accompany commitments to reduce carbon emissions in the EU, the US and other OECD economies. The rationale offered for such border adjustment is that various entities, such as the EU, if making commitments to reduce emissions which go beyond those undertaken in other regions of the world, impose added costs on domestic producers which create a competitive disadvantage for them. Some form of remedy is viewed as reasonable to maintain the competitiveness of domestic industries when responding to global environmental problems. In this paper, we argue that despite its current carbon manifestation, the issue of border tax adjustments and both their rationale and their effects on trade are not new and, despite the present debate (which seems to overlook older literature), have arisen before. Earlier debate on border tax adjustments occurred at the time of the adoption of the Value Added Tax (VAT) in the EU as a tax harmonization target in the early 1960’s. But academic literature of the time showed that a change between origin and destination basis in the VAT would be neutral and hence the use of a destination based tax in the EU to accompany the VAT offered no trade advantage to Europe. Here we argue that essentially the same arguments also apply for carbon motivated BTAs, and in the current debate there seems to be a misconception between price level effects and relative price effects stemming from a BTA, which needs correcting. We also argue that the impact of border tax adjustments should be viewed as independent of the motivation of the adjustments.

Revealing ensemble state transition patterns in multi-electrode neuronal recordings using hidden Markov models

In order to harness the computational capacity of dissociated cultured neuronal networks, it is necessary to understand neuronal dynamics and connectivity on a mesoscopic scale. To this end, this paper uncovers dynamic spatiotemporal patterns emerging from electrically stimulated neuronal cultures using hidden Markov models (HMMs) to characterize multi-channel spike trains as a progression of patterns of underlying states of neuronal activity. However, experimentation aimed at optimal choice of parameters for such models is essential and results are reported in detail. Results derived from ensemble neuronal data revealed highly repeatable patterns of state transitions in the order of milliseconds in response to probing stimuli

A cannabigerol-rich Cannabis sativa extract, devoid of ∆9-tetrahydrocannabinol, elicits hyperphagia in rats

Objective: Non-psychoactive phytocannabinoids (pCBs) from Cannabis sativa may represent novel therapeutic options for cachexia due to their pleiotropic pharmacological activities, including appetite stimulation. We have recently shown that purified cannabigerol (CBG) is a novel appetite stimulant in rats. As standardised extracts from Cannabis chemotypes dominant in one pCB (botanical drug substances (BDS)) often show greater efficacy and/or potency than purified pCBs, we investigated the effects of a CBG-rich BDS, devoid of psychoactive ∆9-THC, on feeding behaviour. Methods: Following a 2 hour pre-feed satiation procedure, 16 male Lister-hooded rats were administered CBG-BDS (at 30-240 mg/kg) or vehicle. Food intake, meal pattern microstructure and locomotor activity were recorded over 2 hours. Results: Total food intake was increased by 120 and 240mg/kg CBG-BDS vs vehicle (1.53g and 1.36g, respectively, vs 0.56g; p<0.05 and p<0.01). Latency to feeding onset was dose-dependently decreased by all doses (p<0.05-0.01), and 120 and 240mg/kg doses increased both the number of meals consumed (p<0.01) and cumulative size of the first 2 meals (p<0.05 and p<.0.01). No significant effect was observed on ambulatory activity or rearing behaviour. Conclusions: CBG-BDS is a novel appetite stimulant, which may have greater potency than purified CBG, despite the absence of ∆9-THC in the extract

Childhood IQ and marriage by mid-life: the Scottish Mental Survey 1932 and the Midspan Studies

The study examined the influence of IQ at age 11 years on marital status by mid-adulthood. The combined databases of the Scottish Mental Survey 1932 and the Midspan studies provided data from 883 subjects. With regard to IQ at age 11, there was an interaction between sex and marital status by mid-adulthood (p &#61; 0.0001). Women who had ever-married achieved mean lower childhood IQ scores than women who had never-married (p &#60; 0.001). Conversely, there was a trend for men who had ever-married to achieve higher childhood IQ scores than men who had never-married (p &#61; 0.07). In men, the odds ratio of ever marrying was 1.35 (95&#37; CI 0.98–1.86&#59; p &#61; 0.07) for each standard deviation increase in childhood IQ. Among women, the odds ratio of ever marrying by mid-life was 0.42 (95&#37; CI 0.27–0.64; p &#61; 0.0001) for each standard deviation increase in childhood IQ. Mid-life social class had a similar association with marriage, with women in more professional jobs and men in more manual jobs being less likely to have ever-married by mid-life. Adjustment for the effects of mid-life social class and height on the association between childhood IQ and later marriage, and vice versa, attenuated the effects somewhat, but suggested that IQ, height and social class acted partly independently

Normative Minor Childhood Stress and Risk of Later Adult Psychopathology in Saudi Arabia

Chronic minor childhood stress in the form of corporal punishment predicts adult psychopathology in the United States but has not been demonstrated in a country where corporal punishment is normative. We tested whether adult psychopathology was predicted by recalled frequency of childhood corporal punishment and recalled controllability of punishment in Saudi Arabia. Two hundred and fifty nine Saudi men with substance addictions (who for cultural reasons were at risk for depression) completed a survey measuring: demographic variables, frequency of beating and controllability of punishment as a child, depression and borderline personality disorder symptoms (BPD). Beating frequency and punishment control were uncorrelated and unrelated to patients’ or parents’ education. 92 men (36%) had major depression (PHQ-9 ≥15). Compared to those never beaten, those experiencing infrequent beating (once or twice a year) were significantly more likely to have major depression and higher BPD symptoms, after controlling for demographic variables. Those experiencing frequent beating (monthly or more frequent) were more likely to have major depression and higher BDP symptoms compared to those never beaten, but only when perceived control was low. Perceived punishment control was not significantly related to outcome for those who never had or had infrequent corporal punishment. These results provide evidence in a culture where corporal punishment is normative that corporal punishment, even when infrequent, predisposes to adult psychopathology and that uncontrollability increases the pathogenic effect of frequent corporal punishment. These results support the hypothesis that frequent minor stressors in childhood act as kindling factor for later depression

“I can’t skip it”: does free report improve accuracy in false memories?

Strategic monitoring of recognition memory by children and adults was examined using a semantic DRM procedure. Children (7- and 10-year-olds) and adults (overall N?=?393) studied lists of semantically related words either incidentally or intentionally and were tested with old items, new items and critical lures to judge as old or new. Participants either made a decision about every item they saw (forced report), or they had the opportunity to withhold answers they were uncertain about (free report). Children were less likely to withhold an answer than adults. However, 7-year-olds were more able to resist false memories when given the opportunity to withhold an answer compared to 10-year-olds or adults. In contrast, adults were unable to improve false memory accuracy. These data suggest that once semantically induced false memories have been encoded they are amenable to strategic monitoring at retrieval in children but not adults

Cannabidiol (CBD) improves survival and behavioural comorbidities of Dravet syndrome in mice

Background and Purpose Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and comorbidities such as anxiety, depression, autism, motor dysfunction, and memory deficits. Cannabidiol is an approved anticonvulsive drug in USA and Europe for seizures associated with Dravet syndrome therapy in patients 2 years of age and older; we investigated its potential to prevent premature mortality and improve associated comorbidities. Experimental Approach The efficacy of sub-chronic cannabidiol administration in two mouse models which reproduce characteristics of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a-/- mice. We then used a hybrid, heterozygote Scn1a+/- mouse model to study the effect of cannabidiol on survival and behavioural comorbidities; motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test). Key Results In Scn1a-/- mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a+/- mice chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours. Conclusion and Implications We are the first to demonstrate a potential disease-modifying effect of cannabidiol in animal models of Dravet syndrome. cannabidiol treatment reduced premature mortality and improved several behavioural comorbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural comorbidities associated with Dravet syndrome

A fibre alginate co-culture platform for the differentiation of mESC and modelling of the neural tube

Alginate hydrogels are a commonly used substrate for in vitro 3D cell culture. These naturally derived biomaterials are highly tunable, biocompatible and can be designed to mimic the elastic modulus of the adult brain at 1% w/v solution. Recent studies show that the molecular weight of the alginate can affect cell viability and differentiation. The relationship between the molecular weight, viscosity and ratio of G:M monomers of alginate hydrogels is complex, and the balance between these factors must be carefully considered when deciding on a suitable alginate hydrogel for stem cell research. This study investigates the formation of embryoid bodies (EB) from mouse embryonic stem cells, using low molecular weight (LMW) and high molecular weight (HMW) alginates. The cells are differentiated using a retinoic acid-based protocol, and the resulting aggregates are sectioned and stained for the presence of stem cells and the three germ layers (endoderm, mesoderm and ectoderm). The results highlight that aggregates within LMW and HMW alginate are true EBs, as demonstrated by positive staining for markers of the three germ layers. Using tubular alginate scaffolds, formed with an adapted gradient maker protocol, we also propose a novel 3D platform for the patterned differentiation of mESCs, based on gradients of retinoic acid produced in situ by lateral motor column (LMC) motor neurons. The end product of our platform will be of great interest as it can be further developed into a powerful model of neural tube development

Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays

Background Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat (‘artificial animal’) applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Results Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. Conclusions We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role