Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.

Bacillus subtilis natto: a non-toxic source of poly-γ-glutamic acid that could be used as a cryoprotectant for probiotic bacteria

It is common practice to freeze dry probiotic bacteria to improve their shelf life. However, the freeze drying process itself can be detrimental to their viability. The viability of probiotics could be maintained if they are administered within a microbially produced biodegradable polymer - poly-γ-glutamic acid (γ-PGA) - matrix. Although the antifreeze activity of γ-PGA is well known, it has not been used for maintaining the viability of probiotic bacteria during freeze drying. The aim of this study was to test the effect of γ-PGA (produced by B. subtilis natto ATCC 15245) on the viability of probiotic bacteria during freeze drying and to test the toxigenic potential of B. subtilis natto. 10% γ-PGA was found to protect Lactobacillus paracasei significantly better than 10% sucrose, whereas it showed comparable cryoprotectant activity to sucrose when it was used to protect Bifidobacterium breve and Bifidobacterium longum. Although γ-PGA is known to be non-toxic, it is crucial to ascertain the toxigenic potential of its source, B. subtilis natto. Presence of six genes that are known to encode for toxins were investigated: three component hemolysin (hbl D/A), three component non-haemolytic enterotoxin (nheB), B. cereus enterotoxin T (bceT), enterotoxin FM (entFM), sphingomyelinase (sph) and phosphatidylcholine-specific phospholipase (piplc). From our investigations, none of these six genes were present in B. subtilis natto. Moreover, haemolytic and lecithinase activities were found to be absent. Our work contributes a biodegradable polymer from a non-toxic source for the cryoprotection of probiotic bacteria, thus improving their survival during the manufacturing process.

Does convective aggregation need to be represented in cumulus parameterizations?

Tropical deep convection exhibits a variety of levels of aggregation over a wide range of scales. Based on a multisatellite analysis, the present study shows at mesoscale that different levels of aggregation are statistically associated with differing large-scale atmospheric states, despite similar convective intensity and large-scale forcings. The more aggregated the convection, the dryer and less cloudy the atmosphere, the stronger the outgoing longwave radiation, and the lower the planetary albedo. This suggests that mesoscale convective aggregation has the potential to affect couplings between moisture and convection and between convection, radiation, and large-scale ascent. In so doing, aggregation may play a role in phenomena such as “hot spots” or the Madden-Julian Oscillation. These findings support the need for the representation of mesoscale organization in cumulus parameterizations; most parameterizations used in current climate models lack any such representation. The ability of a cloud system-resolving model to reproduce observed relationships suggests that such models may be useful to guide attempts at parameterizations of convective aggregation.

Optokinetic stimulation induces illusory movement of both out-of-the-body and on-the-body hand-held visual objects

The coding of body part location may depend upon both visual and proprioceptive information, and allows targets to be localized with respect to the body. The present study investigates the interaction between visual and proprioceptive localization systems under conditions of multisensory conflict induced by optokinetic stimulation (OKS). Healthy subjects were asked to estimate the apparent motion speed of a visual target (LED) that could be located either in the extrapersonal space (visual encoding only, V), or at the same distance, but stuck on the subject's right index finger-tip (visual and proprioceptive encoding, V-P). Additionally, the multisensory condition was performed with the index finger kept in position both passively (V-P passive) and actively (V-P active). Results showed that the visual stimulus was always perceived to move, irrespective of its out- or on-the-body location. Moreover, this apparent motion speed varied consistently with the speed of the moving OKS background in all conditions. Surprisingly, no differences were found between V-P active and V-P passive conditions in the speed of apparent motion. The persistence of the visual illusion during the active posture maintenance reveals a novel condition in which vision totally dominates over proprioceptive information, suggesting that the hand-held visual stimulus was perceived as a purely visual, external object despite its contact with the hand.

Towards an improved and more flexible representation of water stress in coupled photosynthesis–stomatal conductance models

Coupled photosynthesis–stomatal conductance (A–gs) models are commonly used in ecosystem models to represent the exchange rate of CO2 and H2O between vegetation and the atmosphere. The ways these models account for water stress differ greatly among modelling schemes. This study provides insight into the impact of contrasting model configurations of water stress on the simulated leaf-level values of net photosynthesis (A), stomatal conductance (gs), the functional relationship among them and their ratio, the intrinsic water use efficiency (A/gs), as soil dries. A simple, yet versatile, normalized soil moisture dependent function was used to account for the effects of water stress on gs, on mesophyll conductance (gm) and on the biochemical capacity. Model output was compared to leaf-level values obtained from the literature. The sensitivity analyses emphasized the necessity to combine both stomatal and non-stomatal limitations of A in coupled A–gs models to accurately capture the observed functional relationships A vs. gs and A/gsvs. gs in response to drought. Accounting for water stress in coupled A–gs models by imposing either stomatal or biochemical limitations of A, as commonly practiced in most ecosystem models, failed to reproduce the observed functional relationship between key leaf gas exchange attributes. A quantitative limitation analysis revealed that the general pattern of C3 photosynthetic response to water stress may be well represented in coupled A–gs models by imposing the highest limitation strength to gm, then to gs and finally to the biochemical capacity.

Regulatory hotspots are associated with plant gene expression under varying soil phosphorus supply in Brassica rapa

Gene expression is a quantitative trait that can be mapped genetically in structured populations to identify expression quantitative trait loci (eQTL). Genes and regulatory networks underlying complex traits can subsequently be inferred. Using a recently released genome sequence, we have defined cis- and trans-eQTL and their environmental response to low phosphorus (P) availability within a complex plant genome and found hotspots of trans-eQTL within the genome. Interval mapping, using P supply as a covariate, revealed 18,876 eQTL. trans-eQTL hotspots occurred on chromosomes A06 and A01 within Brassica rapa; these were enriched with P metabolism-related Gene Ontology terms (A06) as well as chloroplast-and photosynthesis-related terms (A01). We have also attributed heritability components to measures of gene expression across environments, allowing the identification of novel gene expression markers and gene expression changes associated with low P availability. Informative gene expression markers were used to map eQTL and P use efficiency-related QTL. Genes responsive to P supply had large environmental and heritable variance components. Regulatory loci and genes associated with P use efficiency identified through eQTL analysis are potential targets for further characterization and may have potential for crop improvement.

Observational and energetics constraints on the non-conservation of potential/Conservative Temperature and implications for ocean modelling

This paper seeks to elucidate the fundamental differences between the nonconservation of potential temperature and that of Conservative Temperature, in order to better understand the relative merits of each quantity for use as the heat variable in numerical ocean models. The main result is that potential temperature is found to behave similarly to entropy, in the sense that its nonconservation primarily reflects production/destruction by surface heat and freshwater fluxes; in contrast, the nonconservation of Conservative Temperature is found to reflect primarily the overall compressible work of expansion/contraction. This paper then shows how this can be exploited to constrain the nonconservation of potential temperature and entropy from observed surface heat fluxes, and the nonconservation of Conservative Temperature from published estimates of the mechanical energy budgets of ocean numerical models. Finally, the paper shows how to modify the evolution equation for potential temperature so that it is exactly equivalent to using an exactly conservative evolution equation for Conservative Temperature, as was recently recommended by IOC et al. (2010). This result should in principle allow ocean modellers to test the equivalence between the two formulations, and to indirectly investigate to what extent the budget of derived nonconservative quantities such as buoyancy and entropy can be expected to be accurately represented in ocean models.

Impact of Interbasin Exchange on the Atlantic Overturning Circulation

The ther mohaline exchange between the Atlantic and the Souther n Ocean is analyzed, using a dataset based on WOCE hydrographic data. It is shown that the salt and heat transports brought about by the South Atlantic subtropical gyre play an essential role in the Atlantic heat and salt budgets. It is found that on average the exported North Atlantic Deep W ater (NADW) is fresher than the retur n flows (basically composed of ther mocline and inter mediate water), indicating that the overtur ning circulation (OC) exports freshwater from the Atlantic. The sensitivity of the OC to interbasin fluxes of heat and salt is studied in a 2 D model, representing the Atlantic between 60 8 N and 30 8 S. The model is forced by mixed boundar y conditions at the sur face, and by realistic fluxes of heat and salt at its 30 8 S boundar y. The model circulation tur ns out to be ver y sensitive to net buoyancy fluxes through the sur face. Both net sur face cooling and net sur face saltening are sources of potential energy and impact positively on the circulation strength. The vertical distributions of the lateral fluxes tend to stabilize the stratification, and, as they extract potential energy from the system, tend to weaken the flow . These results imply that a change in the composition of the NADW retur n transports, whether by a change in the ratio ther mocline/inter mediate water , o r by a change in their ther mohaline characteristics, might influence the Atlantic OC considerably . It is also shown that the circulation is much more sensitive to changes in the shape of the lateral buoyancy flux than to changes in the shape of the sur face buoyancy flux, as the latter does not explicitly impact on the potential energy of the system. It is concluded that interocean fluxes of heat and salt are important for the strength and operation of the Atlantic ther mohaline circulation, and should be correctly represented in models that are used for climate sensitivity studies.

Time-multiplexed Laguerre-Gaussian holographic optical tweezers for biological applications

A ferroelectric liquid crystal spatial light modulator is used to generate up to 24 independently controllable traps in a holographic optical tweezers system using time-multiplexed Fresnel zone plates. For use in biological applications, helical zone plates are used to generate Laguerre-Gaussian laser modes. The high speed switching of the ferroelectric device together with recent advances in computer technology enable fast, smooth movement of traps that can be independently controlled in real time. This is demonstrated by the trapping and manipulation of yeast cells and fungal spores. (c) 2006 Optical Society of America.

Extinction processes in hotspots of avian biodiversity and the targeting of pre-emptive conservation action

Hot spots of endemism are regarded as important global sites for conservation as they are rich in threatened endemic species and currently experiencing extensive habitat loss. Targeting pre-emptive conservation action to sites that are currently relatively intact but which would be vulnerable to particular human activities if they occurred in the future is, however, also valuable but has received less attention. Here, we address this issue by using data on Endemic Bird Areas (EBAs). First, we identify the ecological factors that affect extinction risk in the face of particular human activities, and then use these insights to identify EBAs that should be priorities for pre-emptive conservation action. Threatened endemic species in EBAs are significantly more likely to be habitat specialists or relatively large-bodied than non-threatened species, when compared across avian families. Increasing habitat loss causes a significant increase in extinction risk among habitat specialists, but we found no evidence to suggest that the presence of alien species/human exploitation causes a significant increase in extinction risk among large-bodied species. This suggests that these particular human activities are contributing to high extinction risk among habitat specialists, but not among large-bodied species. Based on these analyses, we identify 39 EBAs containing 570 species (24% of the total in EBAs) that are not currently threatened with severe habitat loss, but would be ecologically vulnerable to future habitat loss should it occur. We show that these sites tend to be poorly represented in existing priority setting exercises involving hot spots, suggesting that vulnerability must be explicitly included within these exercises if such sites are to be adequately protected.

Extinction processes in hot spots of avian biodiversity and the targeting of pre-emptive conservation action

Hot spots of endemism are regarded as important global sites for conservation as they are rich in threatened endemic species and currently experiencing extensive habitat loss. Targeting pre-emptive conservation action to sites that are currently relatively intact but which would be vulnerable to particular human activities if they occurred in the future is, however, also valuable but has received less attention. Here, we address this issue by using data on Endemic Bird Areas (EBAs). First, we identify the ecological factors that affect extinction risk in the face of particular human activities, and then use these insights to identify EBAs that should be priorities for pre-emptive conservation action. Threatened endemic species in EBAs are significantly more likely to be habitat specialists or relatively large-bodied than non-threatened species, when compared across avian families. Increasing habitat loss causes a significant increase in extinction risk among habitat specialists, but we found no evidence to suggest that the presence of alien species/human exploitation causes a significant increase in extinction risk among large-bodied species. This suggests that these particular human activities are contributing to high extinction risk among habitat specialists, but not among large-bodied species. Based on these analyses, we identify 39 EBAs containing 570 species (24% of the total in EBAs) that are not currently threatened with severe habitat loss, but would be ecologically vulnerable to future habitat loss should it occur. We show that these sites tend to be poorly represented in existing priority setting exercises involving hot spots, suggesting that vulnerability must be explicitly included within these exercises if such sites are to be adequately protected.