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.

Effects of second language on cognition in English users of L2 Japanese

It is now established that certain cognitive processes such as categorisation are tightly linked to the concepts encoded in language. Recent studies have shown that bilinguals with languages that differ in their concepts may show a shift in their cognition towards the L2 pattern primarily as a function of their L2 proficiency. This research has so far focused predominantly on L2 users who started learning the L2 in childhood or early puberty. The current study asks whether similar effects can be found in adult L2 learners. English speakers of L2 Japanese were given an object classification task involving real physical objects, and an online classification task involving artificial novel objects. Results showed a shift towards the L2 pattern, indicating that some degree of cognitive plasticity exists even when a second language is acquired later in life. These results have implications for theories of L2 acquisition and bilingualism, and contribute towards our understanding of the nature of the relationship between language and cognition in the L2 user’s mind.

The Liberal Way of War? French representations of the Allies, 1944-2008

This chapter looks at the ways in which Anglo-American participants in the Liberation of France have been represented in French narratives in the decades since the Second World War, through the developing French historiography of Allied participation in the War, and through the various roles assigned to the Allies in key postwar memorialisation ceremonies in France.

The politics of temporary work deregulation in Europe: solving the French puzzle

Temporary work has expanded in the last three decades with adverse implications for inequalities. Because temporary workers are a constituency that is unlikely to impose political costs, governments often choose to reduce temporary work regulations. While most European countries have indeed implemented such reforms, France went in the opposite direction, despite having both rigid labour markets and high unemployment. My argument to solve this puzzle is that where replaceability is high, workers in permanent and temporary contracts have overlapping interests, and governments choose to regulate temporary work to protect permanent workers. In turn, replaceability is higher where permanent workers’ skills are general and wage coordination is low. Logistic regression analysis of the determinants of replaceability — and how this affects governments’ reforms of temporary work regulations — supports my argument. Process tracing of French reforms also confirm that the left has tightened temporary work regulations to compensate for the high replaceability.

The 'child of Babylon' and the problem of paternity in Medieval French Alexander romances

A study of the use of hybrid physical appearance both to signal and to explore the disputed paternity of Alexander the Great throughout its vernacular French tradition. The article compares the 'child of Babylon' portent and Alexander's son Alior in the twelfth-century French "Roman d'Alexandre" poem cycle, and a fifteenth-century prose adaptation of it.

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.

The role of context in forming young learners' attitudes and motivation to learning French

Despite the wealth of valuable information that has been generated by motivation studies to date, there are certain limitations in the common approaches. Quantitative and psychometric approaches to motivation research that have dominated in recent decades provided epiphenomenal descriptions of learner motivation within different contexts. However, these approaches assume homogeneity within a given group and often mask the variation between learners within the same, and different, contexts. Although these studies have provided empirical data to form and validate theoretical constructs, they have failed to recognise learners as individual ‘people’ that interact with their context. Learning context has become increasingly explicit in motivation studies, (see Coleman et al. 2007 and Housen et al. 2011), however it is generally considered as a background variable which is pre-existing and external to the individual. Stemming from the recent ‘social turn’ (Block 2003) in SLA research from a more cognitive-linguistic perspective to a more context-specific view of language learning, there has been an upsurge in demand for a greater focus on the ‘person in context’ in motivation research (Ushioda 2011). This paper reports on the findings of a longitudinal study of young English learners of French as they transition from primary to secondary school. Over 12 months, the study employed a mixed-method approach in order to gain an in-depth understanding of how the learners’ context influenced attitudes to language learning. The questionnaire results show that whilst the learners displayed some consistent and stable motivational traits over the 12 months, there were significant differences for learners within different contexts in terms of their attitudes to the language classroom and their levels of self-confidence. A subsequent examination of the qualitative focus group data provided an insight into how and why these attitudes were formed and emphasised the dynamic and complex interplay between learners and their context.