Apheresis donors and platelet function: inherent platelet responsiveness influences platelet quality

BACKGROUND: Process-induced platelet (PLT) activation occurs with all production methods, including apheresis. Recent studies have highlighted the range and consistence of interindividual variation in the PLT response, but little is known about the contribution of a donors' inherent PLT responsiveness to the activation state of the apheresis PLTs or the effect of frequent apheresis on donors' PLTs. STUDY DESIGN AND METHODS: The relationship between the donors' PLT response on the apheresis PLTs was studied in 47 individuals selected as having PLTs with inherently low, intermediate, or high responsiveness. Whole-blood flow cytometry was used to measure PLT activation (levels of bound fibrinogen) before donation and in the apheresis PLTs. The effects of regular apheresis on the activation status of donors' PLTs were studied by comparing the in vivo activation status of PLTs from apheresis (n = 349) and whole-blood donors (n = 157), before donation. The effect of apheresis per se on PLT activation was measured in 10 apheresis donors before and after donation. RESULTS: The level of PLT activation in the apheresis packs was generally higher than in the donor, and the most activated PLTs were from high-responder donors. There was no significant difference in PLT activation before donation between the apheresis and whole-blood donors (p = 0.697), and there was no consistent evidence of activation in the donors immediately after apheresis. CONCLUSION: The most activated apheresis PLTs were obtained from donors with more responsive PLTs. Regular apheresis, however, does not lead to PLT activation in the donors.

Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

Weaning diet induces sustained metabolic phenotype shift in the pig and influences host response to Bifidobacterium lactis NCC2818

Background: The process of weaning causes a major shift in intestinal microbiota and is a critical period for developing appropriate immune responses in young mammals. Objective: To use a new systems approach to provide an overview of host metabolism and the developing immune system in response to nutritional intervention around the weaning period. Design: Piglets (n¼14) were weaned onto either an eggbased or soya-based diet at 3 weeks until 7 weeks, when all piglets were switched onto a fish-based diet. Half the animals on each weaning diet received Bifidobacterium lactis NCC2818 supplementation from weaning onwards. Immunoglobulin production from immunologically relevant intestinal sites was quantified and the urinary 1H NMR metabolic profile was obtained from each animal at post mortem (11 weeks). Results: Different weaning diets induced divergent and sustained shifts in the metabolic phenotype, which resulted in the alteration of urinary gut microbial co-metabolites, even after 4 weeks of dietary standardisation. B lactis NCC2818 supplementation affected the systemic metabolism of the different weaning diet groups over and above the effects of diet. Additionally, production of gut mucosa-associated IgA and IgM was found to depend upon the weaning diet and on B lactis NCC2818 supplementation. Conclusion: The correlation of urinary 1H NMR metabolic profile with mucosal immunoglobulin production was demonstrated, thus confirming the value of this multiplatform approach in uncovering non-invasive biomarkers of immunity. This has clear potential for translation into human healthcare with the development of urine testing as a means of assessing mucosal immune status. This might lead to early diagnosis of intestinal dysbiosis and with subsequent intervention, arrest disease development. This system enhances our overall understanding of pathologies under supra-organismal control.

Direct experimental evidence that early-life farm environment influences regulation of immune responses

Background: In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment. Methods: Piglets were nursed by their mother on a commercial farm, while isolatorreared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. Results: There was more CD4+ and CD4+CD25+ effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4+CD25+Foxp3+ regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to-effector ratio in the farm animals. Consistent with these findings, isolator-reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets. Conclusion: Here, we provide the first direct evidence, derived from intervention, that components of the early-life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.

Influences of increasing temperature on Indian wheat: quantifying limits to predictability

As climate changes, temperatures will play an increasing role in determining crop yield. Both climate model error and lack of constrained physiological thresholds limit the predictability of yield. We used a perturbed-parameter climate model ensemble with two methods of bias-correction as input to a regional-scale wheat simulation model over India to examine future yields. This model configuration accounted for uncertainty in climate, planting date, optimization, temperature-induced changes in development rate and reproduction. It also accounts for lethal temperatures, which have been somewhat neglected to date. Using uncertainty decomposition, we found that fractional uncertainty due to temperature-driven processes in the crop model was on average larger than climate model uncertainty (0.56 versus 0.44), and that the crop model uncertainty is dominated by crop development. Simulations with the raw compared to the bias-corrected climate data did not agree on the impact on future wheat yield, nor its geographical distribution. However the method of bias-correction was not an important source of uncertainty. We conclude that bias-correction of climate model data and improved constraints on especially crop development are critical for robust impact predictions.

Atmospheric blocking in a high resolution climate model: influences of mean state, orography and eddy forcing

An underestimate of atmospheric blocking occurrence is a well-known limitation of many climate models. This article presents an analysis of Northern Hemisphere winter blocking in an atmospheric model with increased horizontal resolution. European blocking frequency increases with model resolution, and this results from an improvement in the atmospheric patterns of variability as well as a simple improvement in the mean state. There is some evidence that the transient eddy momentum forcing of European blocks is increased at high resolution, which could account for this. However, it is also shown that the increase in resolution of the orography is needed to realise the improvement in blocking, consistent with the increase in height of the Rocky Mountains acting to increase the tilt of the Atlantic jet stream and giving higher mean geopotential heights over northern Europe. Blocking frequencies in the Pacific sector are also increased with atmospheric resolution, but in this case the improvement in orography actually leads to a decrease in blocking

APOA5 genotype influences the association between 25-hydroxyvitamin D and high density lipoprotein cholesterol

OBJECTIVE: Circulating levels of 25-hydroxyvitamin D (25OHD) are positively associated with high density lipoprotein (HDL) cholesterol. We sought to replicate a previously reported interaction between APOA5 genotype and vitamin D, and to examine whether HDL-associated genetic loci modify the association between serum 25OHD and HDL cholesterol. METHODS: We examined whether 42 single nucleotide polymorphisms (SNPs) modify the association between serum 25OHD and HDL cholesterol in the 1958 British Birth cohort (aged 45 years, n = 4978). RESULTS: We identified a borderline interaction between the SNP rs12272004 (near the APOA5) and serum 25OHD on HDL cholesterol (P(interaction) = 0.05). The interaction was particularly prominent among the samples collected during winter (P(interaction) = 0.001). None of the other loci showed an interaction with serum 25OHD concentrations on HDL cholesterol. CONCLUSIONS: Our study in 4978 British Whites provides further support that APOA5 genotype modifies the association between vitamin D metabolites and HDL cholesterol.

Does orthogonalization really purge equity based property valuations of their general stock market influences?

This paper uses a recently developed nonlinear Granger causality test to determine whether linear orthogonalization really does remove general stock market influences on real estate returns to leave pure industry effects in the latter. The results suggest that there is no nonlinear relationship between the US equity-based property index returns and returns on a general stock market index, although there is evidence of nonlinear causality for the corresponding UK series.

A longitudinal investigation of maternal influences on the development of child hostile attributions and aggression

Aggression in children is associated with an enhanced tendency to attribute hostile intentions to others. However, limited information is available regarding the factors that contribute to the development of such hostile attribution tendencies. We examined factors that contribute to individual differences in child hostile attributions and aggression, focusing on potential pathways from maternal hostile attributions via negative parenting behavior. We conducted a longitudinal study of 98 mothers and children (47 male, 51 female), recruited from groups experiencing high and low levels of psychosocial adversity. Maternal hostile attributions, observed parenting, and child behaviour were assessed at 18 months and 5 years child age, and child hostile attributions were also examined at 5 years. Independent assessments of maternal and child processes were utilized where possible. Analyses provided support for a direct influence of maternal hostile attributions on the development of child hostile attributions and aggressive behaviour. Maternal hostile attributions were also associated with negative parenting behaviour, which in turn influenced child adjustment. Even taking account of possible parenting influences and preexisting child difficulties, hostile attributions in the mother showed a direct link with child aggression at 5 years. Maternal hostile attributions were themselves related to psychosocial adversity. We conclude that maternal hostile attributions are prevalent in high-risk samples and are related to less optimal parenting behaviour, child hostile attributions, and child aggression. Targeting hostile maternal cognitions may be a useful adjunct to parenting programs

Serotonergic activity influences the cognitive appraisal of close intimate relationships in healthy adults

Our results suggest that central serotonin activity influences the appraisal of close intimate partnerships, raising the possibility that serotonergic dysfunction contributes to altered cognitions about relationships in psychiatric illnesses.

Cognitive influences on the affective representation of touch and the sight of touch in the human brain

We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, 'Rich moisturizing cream' or 'Basic cream', while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.

Can perceptual differences account for managerial success?: the case of Japanese aid workers

Purpose – There is a wealth of studies which suggest that managers' positive perceptions/expectations can considerably influence the organisational performance; unfortunately, little empirical evidence has been obtained from development studies. This research aims to focus on the perceptual and behavioural trait differences of successful and unsuccessful aid workers, and their relationship with organisational performance. Design/methodology/approach – Through web-based survey, 244 valid responses were obtained from the Japan International Cooperation Agency (JICA)-aid managers worldwide. Five perception related factors were extracted and used for cluster analysis to group the respondents. Each cluster's perception/behaviour-related factors and organisational performance variables were compared by ANOVA. Findings – It was discovered that Japanese's positive perception/expectation about work and their local colleagues was related to higher organisational performance, and conversely, the negative perception on their part was generally associated with negative behaviour and lower organisational performance. Moreover, in a development context, lower work-related stress and feelings of resignation toward work were strongly associated with the acceptability of cross-cultural work environment. Practical implications – The differences in perceptual tendencies suggest that cautious consideration is advised since these findings may mainly apply to Japanese aid managers. However, as human nature is universal, positive perception and behaviour would bring out positive output in most organisations. Originality/value – This study extended the contextualised “Pygmalion effect” and has clarified the influence of perception/expectation on counter-part behaviour and organisational performance in development aid context, where people-related issues have often been ignored. This first-time research provides imperial data on the significant role of positive perception on the incumbent role holder.

Review of recent research (1998-2012) in German for Academic Purposes (GAP) in comparison with English for Academic Purposes (EAP): cross-influences, synergies and implications for further research

This state-of-the-art review reports on the major studies conducted in the field of Deutsch als Wissenschaftssprache (academic German) since the late 1990s. To begin with, the current position of German as a language of academic communication nationally and internationally will be discussed, focusing especially on the challenges posed by the status of English as a lingua franca. Subsequently, the major research undertaken since the late 1990s will be reviewed and its contribution to the development of teaching materials evaluated. Since studies on academic German have been influenced, to some extent, by research in English for Academic Purposes (EAP), this paper also attempts to dovetail developments in EAP in order to highlight commonalties and differences. The final sections will discuss some potential synergies and implications for further research in both fields.

Potential influences on the United Kingdom's floods of winter 2013/14

During the winter of 2013/14, much of the UK experienced repeated intense rainfall events and flooding. This had a considerable impact on property and transport infrastructure. A key question is whether the burning of fossil fuels is changing the frequency of extremes, and if so to what extent. We assess the scale of the winter flooding before reviewing a broad range of Earth system drivers affecting UK rainfall. Some drivers can be potentially disregarded for these specific storms whereas others are likely to have increased their risk of occurrence. We discuss the requirements of hydrological models to transform rainfall into river flows and flooding. To determine any general changing flood risk, we argue that accurate modelling needs to capture evolving understanding of UK rainfall interactions with a broad set of factors. This includes changes to multiscale atmospheric, oceanic, solar and sea-ice features, and land-use and demographics. Ensembles of such model simulations may be needed to build probability distributions of extremes for both pre-industrial and contemporary concentration levels of atmospheric greenhouse gases.

TNF-α influences the lateral dynamics of TNF receptor I in living cells

In mammalian cells, inflammation is mainly mediated by the binding of tumor necrosis factor alpha to tumor necrosis factor receptor 1. In this study, we investigated lateral dynamics of TNF-R1 before and after ligand binding using high-density single-particle tracking in combination with photoactivated localization microscopy. Our single-molecule data indicates the presence of tumor necrosis factor receptor 1 with different mobilities in the plasma membrane, suggesting different molecular organizations. Cholesterol depletion led to a decrease of slow receptor species and a strong increase in the average diffusion coefficient. Moreover, as a consequence of tumor necrosis factor-alpha treatment, the mean diffusion coefficient moderately increased while its distribution narrowed. Based on our observation, we propose a refined mechanism on the structural arrangement and activation of tumor necrosis factor receptor 1 in the plasma membrane.