Recent lake-level and outflow variations at Lake Viljandi, Estonia: validation of a coupled lake-catchment modelling scheme for climate change studies

Changes in the depth of Lake Viljandi between 1940 and 1990 were simulated using a lake water and energy-balance model driven by standard monthly weather data. Catchment runoff was simulated using a one-dimensional hydrological model, with a two-layer soil, a single-layer snowpack, a simple representation of vegetation cover and similarly modest input requirements. Outflow was modelled as a function of lake level. The simulated record of lake level and outflow matched observations of lake-level variations (r = 0.78) and streamflow (r = 0.87) well. The ability of the model to capture both intra- and inter-annual variations in the behaviour of a specific lake, despite the relatively simple input requirements, makes it extremely suitable for investigations of the impacts of climate change on lake water balance.

Palaeoenvironmental changes during the Valanginian: new insights from variations in phosphorus contents and bulk- and clay mineralogies in the western Tethys

Paleoenvironmental and paleoclimatic changes during the Valanginian carbon isotopic excursion (CIE) have been investigated in the western Tethys. For this purpose, bulk-rock and clay mineralogies, as well as phosphorus (P) contents were evaluated in a selection of five sections located in the Vocontian Basin (Angles, SE France; Alvier, E Switzerland; Malleval, E France), and the Lombardian Basin (Capriolo, N Italy; Breggia, S Switzerland). Within the CIE interval, bulk-rock and clay mineralogies are inferred to reflect mostly climate change. The onset of the CIE (Busnardoites campylotoxus ammonite Zone) is characterized by higher detrital index (DI: sum of the detrital minerals divided by calcite contents) values and the presence of kaolinite in their clay-mineral assemblages. In the late Valanginian (from the Saynoceras verrucosum Zone up to the end of the Valanginian), the samples show relatively variable DI and lower values or the absence of kaolinite. The variation in the mineralogical composition is interpreted as reflecting a change from a climate characterized by optimal weathering conditions associated with an increase in terrigenous input on the southern European margin during the CIE towards an overall unstable climate associated with drier conditions in the late Valanginian. This is contrasted by a dissymmetry (proximal vs distal) along the studied transect, the northern Tethyan margin being more sensitive to changes in continental input compared to the distal environments. P accumulation rates (PAR) present similar features. In the Vocontian basin, P content variations are associated with changes in terrigenous influx, whereas in the Lombardian basin (i.e. Capriolo and Breggia), PAR values are less well correlated. This is mainly because the deeper part of the Tethys was less sensitive to changes in continental inputs. The onset of the CIE (top of the B. campylotoxus Zone) records a general increase in PAR suggesting an increase in marine nutrient levels. This is linked to higher continental weathering rates and the enhanced influx of nutrients into the ocean. In the period corresponding to the shift itself, P contents show a dissymmetry between the Vocontian and Lombardian basins (proximal vs distal). For the sections of Malleval, Alvier and Angles, a decrease in P concentrations associated to a decrease in detrital input is observed. In Capriolo and Breggia, PAR show maximum values during the plateau, indicating a more complex interaction between different P sources. The time interval including the top of S. verrucosum Zone up to the end of the Valanginian is characterized by variable PAR values, suggesting variable nutrient influxes. These changes are in agreement with an evolution towards seasonally contrasted conditions in the late Valanginian.

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.

Verbal short‐term memory performance in pupils with Down Syndrome

Research has shown that verbal short‐term memory span is shorter in individuals with Down syndrome than in typically developing individuals of equivalent mental age, but little attention has been given to variations within or across groups. Differences in the environment and in particular educational experiences may play a part in the relative ease or difficulty with which children remember verbal material. This article explores the performance of 26 Egyptian pupils with Down syndrome and 26 Egyptian typically developing children on two verbal short‐term memory tests: digit recall and non‐word repetition tasks. The findings of the study revealed that typically developing children showed superior performance on these tasks to that of pupils with Down syndrome, whose performance was both lower and revealed a narrower range of attainment. Comparisons with the performance of children with Down syndrome in this study suggested that not only did the children with Down syndrome perform more poorly than the typically developing children, their profile also appeared worse than the results of studies of children with a similar mental age with Down syndrome carried out in western countries. The results from this study suggested that, while deficits in verbal short‐term memory in Down syndrome may well be universal, it is important to recognise that performances may vary as a consequence of culture and educational experiences. The significance of these findings is explored with reference to approaches to education and how these are conceptualised in relation to children with disabilities.

Time-variations in commodity price jumps

In this paper, we study jumps in commodity prices. Unlike assumed in existing models of commodity price dynamics, a simple analysis of the data reveals that the probability of tail events is not constant but depends on the time of the year, i.e. exhibits seasonality. We propose a stochastic volatility jump–diffusion model to capture this seasonal variation. Applying the Markov Chain Monte Carlo (MCMC) methodology, we estimate our model using 20 years of futures data from four different commodity markets. We find strong statistical evidence to suggest that our model with seasonal jump intensity outperforms models featuring a constant jump intensity. To demonstrate the practical relevance of our findings, we show that our model typically improves Value-at-Risk (VaR) forecasts.

Exploring the effects of genotypical and phenotypical variations in bitter taste sensitivity on perception, liking and intake of brassica vegetables in the UK

Brassicaceous vegetables (BV) have chemoprotective effects and yet consumption of BV in the UK is low. Previous studies suggest perception, liking and intake of BV are influenced by bitter taste sensitivity which this study further explores. Phenotypical taste sensitivity of 136 subjects was classified using propythiouracil (PROP) and sodium chloride and fungiform papillae density (FPD) was measured from tongue images. Polymorphisms of TAS2R38 and gustin (CA6) genes were analysed. Liking and bitterness of four raw vegetables (two BV (broccoli and white cabbage) and two non-BV (spinach and courgette)), as well as habitual consumption, were evaluated. There was a significant association between TAS2R38 genotype and PROP taster status (p<0.0001) and between FPD and PROP taster status (p=0.029). Individuals with greater sensitivity for PROP predominantly had TAS2R38 PAV/PAV genotype and greater FPD. BV were perceived as more bitter than non-BV (p<0.0001) with PAV/PAV subjects perceiving significantly stronger bitter intensity. There was a significant difference in liking for the four vegetables (p=0.002), and between consumers of different TAS2R38 genotype (p=0.0024). Individuals with TAS2R38 AVI/AVI genotype liked BV more. Regarding intake, both PAV/PAV and AVI/AVI individuals consumed more total vegetables and BV than PAV/AVI. Although PROP nontasters tended to consume more vegetables and BV than the other two phenotype groups, liking and vegetable intake were not significantly affected by taste phenotype. Although there was not a significant effect of CA6 genotype on bitterness ratings, there was a significant interaction between CA6 and TAS2R38, and in addition CA6 genotype was significantly associated with BV intake. However, these effects require validation as the proportions of the population with the CA6 G/G genotype was extremely small (7%). Our results confirmed that bitter taste perception in vegetables was influenced by both genotype and phenotype of bitter taste sensitivity. Moreover, our findings demonstrated that neither genotype nor phenotype of taste sensitivity alone accurately predict vegetable liking and intake as demographic factors were found to have a substantial influence.

Coupling an aerosol box model with one-dimensional flow: a tool for understanding observations of new particle formation events

Field observations of new particle formation and the subsequent particle growth are typically only possible at a fixed measurement location, and hence do not follow the temporal evolution of an air parcel in a Lagrangian sense. Standard analysis for determining formation and growth rates requires that the time-dependent formation rate and growth rate of the particles are spatially invariant; air parcel advection means that the observed temporal evolution of the particle size distribution at a fixed measurement location may not represent the true evolution if there are spatial variations in the formation and growth rates. Here we present a zero-dimensional aerosol box model coupled with one-dimensional atmospheric flow to describe the impact of advection on the evolution of simulated new particle formation events. Wind speed, particle formation rates and growth rates are input parameters that can vary as a function of time and location, using wind speed to connect location to time. The output simulates measurements at a fixed location; formation and growth rates of the particle mode can then be calculated from the simulated observations at a stationary point for different scenarios and be compared with the ‘true’ input parameters. Hence, we can investigate how spatial variations in the formation and growth rates of new particles would appear in observations of particle number size distributions at a fixed measurement site. We show that the particle size distribution and growth rate at a fixed location is dependent on the formation and growth parameters upwind, even if local conditions do not vary. We also show that different input parameters used may result in very similar simulated measurements. Erroneous interpretation of observations in terms of particle formation and growth rates, and the time span and areal extent of new particle formation, is possible if the spatial effects are not accounted for.

Intra-strain variations of baroreflex sensitivity in young Wistar-Kyoto rats

Purpose: To compare baroreflex sensitivity among conscious rats of the same strain. Methods: Male WKY rats (eight weeks old) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP) and heart rate (HR). Baroreflex gain was calculated as the ratio between variation of HR in function of the MAP variation (Delta HR/Delta MAP) tested with a depressor dose of sodium nitroprusside (SNP, 50 mu g/kg, iv) and with a pressor dose of phenylephrine (PE, 8 mu g/kg, iv). We divided the rats into four groups: 1) Low bradycardic baroreflex (LB), BG between -1 and -2 bpm/mmHg tested with PE; 2) High bradycardic baroreflex (HB), BG < -2 bpm/mmHg tested with PE; 3) Low tachycardic baroreflex (LT), BG between -1 and -2 bpm/mmHg tested with SNP and; 4) High tachycardic baroreflex (HT), BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p<0.05. Results: Approximately 82% of the rats presented reduced bradycardic reflex while 22 showed attenuated tachycardic reflex. No alterations were noted regarding basal MAP and HR, tachycardic and bradycardic peak and HR range. Conclusions: There was alteration in baroreflex sensitivity among rats of the same strain. Care should be taken when interpreting studies employing WKY as a control for the SHR.

CYP3A5*3A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia

Background: The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on biotransformation of xenobiotics. CYP3A5 SNPs have been associated with variations on enzyme activity that can modify the metabolism of several drugs. Methods: In order to evaluate the influence of CYP3A5 variants on response to lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were selected. After a wash-out period of 4 weeks, individuals were treated with atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA sequencing. Results: >Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non-Africans (*3C: 84.9% and *1D 84.8%, p<0.01). Non-Africans carrying *3A allele (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to atorvastatin than non-*3A allele carriers (p<0.05). Conclusion: CYP3A5*3A allele is associated with reduced cholesterol-lowering response to atorvastatin in non-African individuals. (C) 2008 Elsevier B.V. All rights reserved.

Influence of SCARB1 polymorphisms on serum lipids of hypercholesterolemic individuals treated with atorvastatin

Background: The SR-BI is a key component on the cholesterol metabolism. Polymorphisms in the SR-BI gene (SCARB1) were related with variations on plasma lipoprotein profile and other risk factors for cardiovascular disease. We tested the relationship of 3 SCARB1 single nucleotide polymorphisms (SNPs) with hypercholesterolemia in a Brazilian population and whether these variants can influence lipid-lowering response to atorvastatin. Methods: c.4G>A, c.726+54C>T and c.1050C>T SNPs and serum concentrations of lipid and apolipoproteins were evaluated in 147 hypercholesterolemic (HC) and 185 normolipidemic (NL) unrelated Brazilian subjects. HC patients were treated with atorvastatin (10 mg/day/4 weeks). Results: Frequencies of SCARB1 polymorphisms were similar between the HC and NL groups (p>0.05). The T allele for c.726+54C>T was associated with higher LDL-c in NL and with higher apoB and apoB/apoAI in HC (p<0.05). HC individuals carrying c.1050C allele carriers (CC and CT genotypes) had lower change of total cholesterol, LDL-c, apoB and apoB/apoAI ratio (p<0.05) than the TT genotype carriers in response to atorvastatin. Conclusion: The SCARB1 polymorphisms are related with variations in serum lipids in the Brazilian population and c.1050C>T SNP is associated with lipid-lowering atorvastatin response. (C) 2010 Elsevier B.V. All rights reserved.

Modelling the line variations from the wind-wind shock emissions of WR 30a

The study of Wolf-Rayet stars plays an important role in evolutionary theories of massive stars. Among these objects, similar to 20 per cent are known to be in binary systems and can therefore be used for the mass determination of these stars. Most of these systems are not spatially resolved and spectral lines can be used to constrain the orbital parameters. However, part of the emission may originate in the interaction zone between the stellar winds, modifying the line profiles and thus challenging us to use different models to interpret them. In this work, we analysed the He II lambda 4686 angstrom + C IV lambda 4658 angstrom blended lines of WR 30a (WO4+O5) assuming that part of the emission originate in the wind-wind interaction zone. In fact, this line presents a quiescent base profile, attributed to the WO wind, and a superposed excess, which varies with the orbital phase along the 4.6-d period. Under these assumptions, we were able to fit the excess spectral line profile and central velocity for all phases, except for the longest wavelengths, where a spectral line with constant velocity seems to be present. The fit parameters provide the eccentricity and inclination of the binary orbit, from which it is possible to constrain the stellar masses.

Axillary bud development in pineapple nodal segments correlates with changes on cell cycle gene expression, hormone level, and sucrose and glutamate contents

During the process of lateral organ development after plant decapitation, cell division and differentiation occur in a balanced manner initiated by specific signaling, which triggers the reentrance into the cell cycle. Here, we investigated short-term variations in the content of some endogenous signals, such as auxin, cytokinins (Cks), and other mitogenic stimuli (sucrose and glutamate), which are likely correlated with the cell cycle reactivation in the axillary bud primordium of pineapple nodal segments. Transcript levels of cell cycle-associated genes, CycD2;1, and histone H2A were analyzed. Nodal segments containing the quiescent axillary meristem cells were cultivated in vitro during 24 h after the apex removal and de-rooting. From the moment of stem apex and root removal, decapitated nodal segment (DNS) explants showed a lower indol-3-acetic acid (IAA) concentration than control explants, and soon after, an increase of endogenous sucrose and iP-type Cks were detected. The decrease of IAA may be the primary signal for cell cycle control early in G1 phase, leading to the upregulation of CycD2;1 gene in the first h. Later, the iP-type Cks and sucrose could have triggered the progression to S-phase since there was an increase in H2A expression at the eighth h. DNS explants revealed substantial increase in Z-type Cks and glutamate from the 12th h, suggesting that these mitogens could also operate in promoting pineapple cell cycle progression. We emphasize that the use of non-synchronized tissue rather than synchronous cell suspension culture makes it more difficult to interpret the results of a dynamic cell division process. However, pineapple nodal segments cultivated in vitro may serve as an interesting model to shed light on apical dominance release and the reentrance of quiescent axillary meristem cells into the cell cycle.

Alternative splicing and genetic diversity: silencers are more frequently modified by SNVs associated with alternative exon/intron borders

With the availability of a large amount of genomic data it is expected that the influence of single nucleotide variations (SNVs) in many biological phenomena will be elucidated. Here, we approached the problem of how SNVs affect alternative splicing. First, we observed that SNVs and exonic splicing regulators (ESRs) independently show a biased distribution in alternative exons. More importantly, SNVs map more frequently in ESRs located in alternative exons than in ESRs located in constitutive exons. By looking at SNVs associated with alternative exon/intron borders (by their common presence in the same cDNA molecule), we observed that a specific type of ESR, the exonic splicing silencers (ESSs), are more frequently modified by SNVs. Our results establish a clear association between genetic diversity and alternative splicing involving ESSs.

Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies

Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.

EFFECT OF COLD FRONTS ON THE BENTHIC MACROFAUNA OF EXPOSED SANDY BEACHES WITH CONTRASTING MORPHODYNAMICS

The aim of this study was to determine the short-term environmental changes caused by the simultaneous passage of a high energy event on two sandy beaches with different morphodynamic states and their influence on the richness, abundance and distribution of the benthic macrofauna. Two microtidal exposed sandy beaches with contrasting morphodynamics were simultaneously sampled before, during and after the passage of two cold fronts in Santa Catarina. The reflective beach showed a higher susceptibility to the increase in wave energy produced by the passage of cold fronts and was characterized by rapid and intense erosive processes in addition to a capacity for rapid restoration of the beach profile. As regards the dissipative beach, erosive processes operated more slowly and progressively, and it was characterized further by a reduced capacity for the recovery of its sub-aerial profile. Although the intensity of the environmental changes was distinct as between the morphodynamic extremes, changes in the composition, richness and abundance of macrobenthos induced by cold fronts were not evident for either of the beaches studied. On the other hand, alterations in the distribution pattern of the macrofauna were observed on the two beaches and were related to variations in sea level, position of the swash zone and moisture gradient, suggesting that short-term accommodations in the spatial structure of the macrobenthos occur in response to changes in environmental conditions in accordance with the temporal dynamics characteristic of each morphodynamic state.