Antidepressant treatment and emotional processing: can we dissociate the roles of serotonin and noradrenaline?

The ability to match individual patients to tailored treatments has the potential to greatly improve outcomes for individuals suffering from major depression. In particular, while the vast majority of antidepressant treatments affect either serotonin or noradrenaline or a combination of these two neurotransmitters, it is not known whether there are particular patients or symptom profiles which respond preferentially to the potentiation of serotonin over noradrenaline or vice versa. Experimental medicine models suggest that the primary mode of action of these treatments may be to remediate negative biases in emotional processing. Such models may provide a useful framework for interrogating the specific actions of antidepressants. Here, we therefore review evidence from studies examining the effects of drugs which potentiate serotonin, noradrenaline or a combination of both neurotransmitters on emotional processing. These results suggest that antidepressants targeting serotonin and noradrenaline may have some specific actions on emotion and reward processing which could be used to improve tailoring of treatment or to understand the effects of dual-reuptake inhibition. Specifically, serotonin may be particularly important in alleviating distress symptoms, while noradrenaline may be especially relevant to anhedonia. The data reviewed here also suggest that noradrenergic-based treatments may have earlier effects on emotional memory that those which affect serotonin.

Can we predict when “dying” will be difficult?: Progressive achievements in L2 English

A large body of research has focused on the observation that second language (L2) learners are limited in their production of temporal and aspectual forms. For example, in L2 English, it has been shown learners use progressive marking with activity verbs and only rarely extend the form to telic verb phrases such as accomplishments or achievements (Bardovi-Harlig and Reynolds, 1995; Bardovi-Harlig, 2000; Robison, 1995). Shirai and Andersen (1995) proposed that activities represent the prototype for the category of progressive aspect and learners generally acquire the prototype first. However, very little research has focused explicitly on advanced learners to see if they eventually extend beyond the prototype. In addition, properties of the native language have not systematically been taken into account. Achievements such as "die" are especially interesting in that they interact differently with markers of progressive aspect across languages. The present study investigated the acquisition of progressive achievements in English by native speakers of Chinese and Korean in order to examine whether there is evidence of universal difficulty, as would be predicted by the prototype account, or whether similarity between the L1 and L2 (as in the case of English and Korean) can facilitate acquisition, as would be predicted by transfer. Our results suggest that the properties of the native language play an important role, supporting the transfer account. However, neither L1 group performs at the level of native speakers. We argue that the acquisition of aspect is influenced by both the properties of the native language and the semantic and pragmatic complexity of the target computation.

How well can we measure the ocean’s mean dynamic topography from space?

Recent gravity missions have produced a dramatic improvement in our ability to measure the ocean’s mean dynamic topography (MDT) from space. To fully exploit this oceanic observation, however, we must quantify its error. To establish a baseline, we first assess the error budget for an MDT calculated using a 3rd generation GOCE geoid and the CLS01 mean sea surface (MSS). With these products, we can resolve MDT spatial scales down to 250 km with an accuracy of 1.7 cm, with the MSS and geoid making similar contributions to the total error. For spatial scales within the range 133–250 km the error is 3.0 cm, with the geoid making the greatest contribution. For the smallest resolvable spatial scales (80–133 km) the total error is 16.4 cm, with geoid error accounting for almost all of this. Relative to this baseline, the most recent versions of the geoid and MSS fields reduce the long and short-wavelength errors by 0.9 and 3.2 cm, respectively, but they have little impact in the medium-wavelength band. The newer MSS is responsible for most of the long-wavelength improvement, while for the short-wavelength component it is the geoid. We find that while the formal geoid errors have reasonable global mean values they fail capture the regional variations in error magnitude, which depend on the steepness of the sea floor topography.

What does “retrofit” mean, and how can we scale up action in the UK sector?

Purpose – Progress in retrofitting the UK's commercial properties continues to be slow and fragmented. New research from the UK and USA suggests that radical changes are needed to drive large-scale retrofitting, and that new and innovative models of financing can create new opportunities. The purpose of this paper is to offer insights into the terminology of retrofit and the changes in UK policy and practice that are needed to scale up activity in the sector. Design/methodology/approach – The paper reviews and synthesises key published research into commercial property retrofitting in the UK and USA and also draws on policy and practice from the EU and Australia. Findings – The paper provides a definition of “retrofit”, and compares and contrasts this with “refurbishment” and “renovation” in an international context. The paper summarises key findings from recent research and suggests that there are a number of policy and practice measures which need to be implemented in the UK for commercial retrofitting to succeed at scale. These include improved funding vehicles for retrofit; better transparency in actual energy performance; and consistency in measurement, verification and assessment standards. Practical implications – Policy and practice in the UK needs to change if large-scale commercial property retrofit is to be rolled out successfully. This requires mandatory legislation underpinned by incentives and penalties for non-compliance. Originality/value – This paper synthesises recent research to provide a set of policy and practice recommendations which draw on international experience, and can assist on implementation in the UK.

A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.

Are we there yet? Exploring empowerment at the microscale in the South African wine industry

Empowerment is a standard but ambiguous element of development rhetoric and so, through the socially complex and contested terrain of South Africa, this paper explores its potential to contribute to inclusive development. Investigating micro-level engagements with the national strategy of Broad-Based Black Economic Empowerment (B-BBEE) in the South African wine industry highlights the limitations, but also potential, of this single domain approach. However, latent paternalism, entrenched interests and a ‘dislocated blackness’ maintain a complex racial politics that shapes both power relations and the opportunities for transformation within the industry. Nonetheless, while B-BBEE may not, in reality, be broad-based its manifestations are contributing to challenging racist structures and normalising changing attitudes. This paper concludes that, to be transformative, empowerment needs to be re-embedded within South Africa as a multi-scalar, multi-dimensional dialogue and, despite the continuation of structural constraints, positions the local as a critical scale at which to initiate broader social change.

Can we have confidence in generic structures?

The system dynamics concept of `generic structure' is dividable into three sub-types. This paper analyses the validity of these three, using both practical and theoretical perspectives. Firstly, a new set of measures is developed for generating validity-`confidence'-amongst a group using generic structures in a practical modelling situation. It is concluded that different confidence criteria are implicitly employed; there is an argument for trading-off model precision and analytical quality for simplicity and ease of use and future research is needed to combine these `process' and `content' aspects of confidence. From a theoretical stance it is shown that with two of the sub-types a scientific notion of confidence is achievable whereas the third (`archetypes') involves merely metaphorical thinking. It is concluded that the theoretical status of archetypes requires further development, whilst ensuring that its benefits are retained.

How well can we model stream phosphorus concentrations in agricultural catchments?

Mechanistic catchment-scale phosphorus models appear to perform poorly where diffuse sources dominate. We investigate the reasons for this for one model, INCA-P, testing model output against 18 months of daily data in a small Scottish catchment. We examine key model processes and provide recommendations for model improvement and simplification. Improvements to the particulate phosphorus simulation are especially needed. The model evaluation procedure is then generalised to provide a checklist for identifying why model performance may be poor or unreliable, incorporating calibration, data, structural and conceptual challenges. There needs to be greater recognition that current models struggle to produce positive Nash–Sutcliffe statistics in agricultural catchments when evaluated against daily data. Phosphorus modelling is difficult, but models are not as useless as this might suggest. We found a combination of correlation coefficients, bias, a comparison of distributions and a visual assessment of time series a better means of identifying realistic simulations.

Arthur et ses barons rebelles: la fin remaniée et abrégée de la Suite Vulgate dans le manuscrit du cycle du Graal, Paris, BNF fr. 344

The ms. Paris, BnF, fr. 344 was produced in Lorraine at the end of the thirteenth century and contains the whole Lancelot-Grail cycle. It presents an abridged version of the end of the Vulgate Sequel to Merlin. The rewriting of the end of the sequel glosses over the romantic episodes of the common version and focuses on the figure of Arthur, a legitimate sovereign and skilful war leader confronted by his barons’ dissidence. From the end of f° 182 to f° 184v°, BnF, fr. 344, narrates the departure of Kings Ban and Bohort for the Continent, the embassy of King Loth and his sons, and the fight against the Saxons of the Christian coalition gathered at Logres for the feast of the Holy Cross. This article shows the ideological implications of the abridgement and the illustration used at the end of the Vulgate Sequel in ms. fr. 344, as it exalts Arthur’s kingship and insists on the rallying, penance and submission of his rebelled vassals.

Foodomics for personalized nutrition: how far are we?

To effectively prevent the onset and reduce mortality from noncommunicable diseases, we must consider every individual as metabolically unique to allow for a personalized management to take place. Diet and gut microbiota are major components of the exposome that interact together with a genetic make-up in a complex interplay to result in an individual’s metabolic phenotype. In this context, foodomics approaches (such as nutrigenetics, nutrimetabolomics, nutritranscriptomics, nutriproteomics and metagenomics) are essential tools to assess an individual’s optimal metabolic space. These have recently been applied to large human cohorts to identify specific gene-metabolite, diet-metabolite and gene–diet interactions. As the gut microbiota is a key player in metabolic homeostasis, we suggest following a holistic investigation of metagenome–hyperbolome–diet interactions, the findings of which will provide the basis for developing personalized nutrition and personalized functional foods. However, examining these three-way interactions will only be possible when the challenge of large datasets integration will be overcome.