Monitoring of CD4(+)CD25(high)IL-7R alpha(high) activated T Cells in Kidney Transplant Recipients

Background and objectives In humans, circulating CD4(+)CD25(high) T cells contain mainly regulatory T cells (Treg; FoxP3(+)IL-7R alpha(low)), but a small subset is represented by activated effector T cells (Tact; FoxP3(-)IL-7R alpha(high)). The balance between Tact and Treg may be important after transplantation. The aim of this study was first to analyze and correlate CD4(+)CD25(high) Tact and Treg with the clinical status of kidney transplant recipients and second to study prospectively the effect of two immunosuppressive regimens on Tact/Treg during the first year after transplantation.Design, setting, participants, & measurements CD4(+)CD25(high) Tact and Treg were analyzed by flow cytometry, either retrospectively in 90 patients greater than 1 year after kidney transplantation (cross-sectional analysis) or prospectively in 35 patients receiving two immunosuppressive regimens after kidney transplantation (prospective analysis).Results A higher proportion of Tact and a lower proportion of Treg were found in the majority of kidney recipients. In chronic Immoral rejection, a strikingly higher proportion of Tact was present. A subgroup of stable recipients receiving calcineurin inhibitor-free immunosuppression (mycophenolate mofetil, azathioprine, or sirolimus) had Tact values that were similar to healthy individuals. In the prospective analysis, the proportion of Tact significantly increased in both immunosuppression groups during the first year after transplantation.Conclusions These data highlight distinct patterns in the proportion of circulating Tact depending on the clinical status of kidney recipients. Moreover, the prospective analysis demonstrated an increase in the proportion of Tact, regardless of the immunosuppressive regimen. The measurement of Tact, in addition to Treg, may become a useful immune monitoring tool after kidney transplantation. Clin J Am Soc Nephrol 6: 2025-2033, 2011. doi: 10.2215/CJN.09611010

Strength and cost of an induced immune response are associated with a heritable melanin-based colour trait in female tawny owls.

1. Melanin pigments provide the most widespread source of coloration in vertebrates, but the adaptive function of such traits remains poorly known. 2. In a wild population of tawny owls (Strix aluco), we investigated the relationships between plumage coloration, which varies continuously from dark to pale reddish, and the strength and cost of an induced immune response. 3. The degree of reddishness in tawny owl feather colour was positively correlated with the concentration of phaeomelanin and eumelanin pigments, and plumage coloration was highly heritable (h(2) = 0.93). No carotenoids were detected in the feathers. 4. In mothers, the degree of melanin-based coloration was associated with antibody production against a vaccine, with dark reddish females maintaining a stronger level of antibody for a longer period of time compared to pale reddish females, but at a cost in terms of greater loss of body mass. 5. A cross-fostering experiment showed that, independent of maternal coloration, foster chicks reared by vaccinated mothers were lighter than those reared by nonvaccinated mothers. Hence, even though dark reddish mothers suffered a stronger immune cost than pale reddish mothers, this asymmetric cost was not translated to offspring growth. 6. Our study suggests that different heritable melanin-based colorations are associated with alternative strategies to resist parasite attacks, with dark reddish individuals investing more resources towards the humoral immune response than lightly reddish conspecifics.

The association between alcohol screening scores and health status in male veterans.

OBJECTIVES: Alcohol use is associated with self-reported health status. However, little is known about the concurrent association between alcohol screening scores and patient perception of health. We evaluated this association in a sample of primarily older male veterans.METHODS: This secondary, cross-sectional analysis included male general medicine outpatients from 7 VA medical centers who returned mailed questionnaires. Screening scores from the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire were divided into 6 categories (0, 1­3, 4­5, 6­7, 8­9, and 10­12). Outcomes included scores on the 8 subscales and 2 component scores of the 36-item Short Form Health Survey (SF-36). Unadjusted and adjusted linear regression models were fit to characterize the association between AUDIT-C categories and SF-36 scores. Models were adjusted for demographic characteristics, smoking, and site?both alone and in combination with 14 self-reported comorbid conditions.RESULTS: Male respondents (n = 24,531; mean age = 63.6 years) represented 69% of those surveyed with the SF-36. After adjustment, a quadratic (inverted U-shaped) relationship was demonstrated between AUDIT-C categories and all SF-36 scores such that patients with AUDIT-C scores 4­5 or 6­7 reported the highest health status, and patients with AUDIT-C scores 0, 8­9, and =10 reported the lowest health status.CONCLUSIONS: Across all measures of health status, patients with the most severe alcohol misuse had significantly poorer health status than those who screened positive for alcohol misuse at mild or moderate levels of severity. The relatively good health status reported by patients with mild-moderate alcohol misuse might interfere with clinicians' acceptance and adoption of guidelines recommending that they counsel these patients about their drinking.

Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases.

Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10(-9)-1.01×10(-12)). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9×10(-3)). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10(-88)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.

Association of smoking and nicotine dependence with pre-diabetes in young and healthy adults.

INTRODUCTION: Several studies have shown an increased risk of type 2 diabetes among smokers. Therefore, the aim of this analysis was to assess the relationship between smoking, cumulative smoking exposure and nicotine dependence with pre-diabetes. METHODS: We performed a cross-sectional analysis of healthy adults aged 25-41 in the Principality of Liechtenstein. Individuals with known diabetes, Body Mass Index (BMI) >35 kg/m² and prevalent cardiovascular disease were excluded. Smoking behaviour was assessed by self-report. Pre-diabetes was defined as glycosylated haemoglobin between 5.7% and 6.4%. Multivariable logistic regression models were done. RESULTS: Of the 2142 participants (median age 37 years), 499 (23.3%) had pre-diabetes. There were 1,168 (55%) never smokers, 503 (23%) past smokers and 471 (22%) current smokers, with a prevalence of pre-diabetes of 21.2%, 20.9% and 31.2%, respectively (p <0.0001). In multivariable regression models, current smokers had an odds ratio (OR) of pre-diabetes of 1.82 (95% confidential interval (CI) 1.39; 2.38, p <0.0001). Individuals with a smoking exposure of <5, 5-10 and >10 pack-years had an OR (95% CI) for pre-diabetes of 1.34 (0.90; 2.00), 1.80 (1.07; 3.01) and 2.51 (1.80; 3.59) (p linear trend <0.0001) compared with never smokers. A Fagerström score of 2, 3-5 and >5 among current smokers was associated with an OR (95% CI) for pre-diabetes of 1.27 (0.89; 1.82), 2.15 (1.48; 3.13) and 3.35 (1.73; 6.48) (p linear trend <0.0001). DISCUSSION: Smoking is strongly associated with pre-diabetes in young adults with a low burden of smoking exposure. Nicotine dependence could be a potential mechanism of this relationship.

A multicase study for the evaluation of a pattern-based visual design process for collaborative learning

Collage is a pattern-based visual design authoring tool for the creation of collaborative learning scripts computationally modelled with IMS Learning Design (LD). The pattern-based visual approach aims to provide teachers with design ideas that are based on broadly accepted practices. Besides, it seeks hiding the LD notation so that teachers can easily create their own designs. The use of visual representations supports both the understanding of the design ideas and the usability of the authoring tool. This paper presents a multicase study comprising three different cases that evaluate the approach from different perspectives. The first case includes workshops where teachers use Collage. A second case implies the design of a scenario proposed by a third-party using related approaches. The third case analyzes a situation where students follow a design created with Collage. The cross-case analysis provides a global understanding of the possibilities and limitations of the pattern-based visual design approach.

Experimental evidence that adult antipredator behaviour is heritable and not influenced by behavioural copying in a wild bird.

Knowledge of the relative importance of genetics and behavioural copying is crucial to appraise the evolvability of behavioural consistencies. Yet, genetic and non-genetic factors are often deeply intertwined, and experiments are required to address this issue. We investigated the sources of variation of adult antipredator behaviour in the Alpine swift (Apus melba) by making use of long-term behavioural observations on parents and cross-fostered offspring. By applying an 'animal model' approach to observational data, we show that antipredator behaviour of adult Alpine swifts was significantly repeatable over lifetime (r = 0.273) and heritable (h(2) = 0.146). Regression models also show that antipredator behaviours differed between colonies and sexes (females were more tame), and varied with the hour and year of capture. By applying a parent-offspring regression approach to 59 offspring that were exchanged as eggs or hatchlings between pairs of nests, we demonstrate that offspring behaved like their biological parents rather than like their foster parents when they were adults themselves. Those findings provide strong evidence that antipredator behaviour of adult Alpine swifts is shaped by genetics and/or pre-hatching maternal effects taking place at conception but not by behavioural copying.

Individual vocal signatures in barn owl nestlings: does individual recognition have an adaptive role in sibling vocal competition?

To compete over limited parental resources, young animals communicate with their parents and siblings by producing honest vocal signals of need. Components of begging calls that are sensitive to food deprivation may honestly signal need, whereas other components may be associated with individual-specific attributes that do not change with time such as identity, sex, absolute age and hierarchy. In a sib-sib communication system where barn owl (Tyto alba) nestlings vocally negotiate priority access to food resources, we show that calls have individual signatures that are used by nestlings to recognize which siblings are motivated to compete, even if most vocalization features vary with hunger level. Nestlings were more identifiable when food-deprived than food-satiated, suggesting that vocal identity is emphasized when the benefit of winning a vocal contest is higher. In broods where siblings interact iteratively, we speculate that individual-specific signature permits siblings to verify that the most vocal individual in the absence of parents is the one that indeed perceived the food brought by parents. Individual recognition may also allow nestlings to associate identity with individual-specific characteristics such as position in the within-brood dominance hierarchy. Calls indeed revealed age hierarchy and to a lower extent sex and absolute age. Using a cross-fostering experimental design, we show that most acoustic features were related to the nest of origin (but not the nest of rearing), suggesting a genetic or an early developmental effect on the ontogeny of vocal signatures. To conclude, our study suggests that sibling competition has promoted the evolution of vocal behaviours that signal not only hunger level but also intrinsic individual characteristics such as identity, family, sex and age.

Human capital and regional development

We investigate the determinants of regional development using a newly constructed database of 1569 sub-national regions from 110 countries covering 74 percent of the world s surface and 97 percent of its GDP. We combine the cross-regional analysis of geographic, institutional, cultural, and human capital determinants of regional development with an examination of productivity in several thousand establishments located in these regions. To organize the discussion, we present a new model of regional development that introduces into a standard migration framework elements of both the Lucas (1978) model of the allocation of talent between entrepreneurship and work, and the Lucas (1988) model of human capital externalities. The evidence points to the paramount importance of human capital in accounting for regional differences in development, but also suggests from model estimation and calibration that entrepreneurial inputs and possibly human capital externalities help understand the data.

Melanin-based colouration predicts natal dispersal in the barn owl, Tyto alba

Searching for a suitable breeding site is an important decision in the life of most animals. The decisions where to settle and how far to travel before doing so depend on many factors. Individual differences in dispersal distance could result from different strategies (e.g. specialists versus generalists), which might result in similar reproductive success in different habitats, or different competitive abilities to acquire a territory close to the natal site. The barn owl is polymorphic in melanic coloration, which is associated with many physiological and behavioural traits such as habitat choice, stress response and docility, raising the possibility that the coloration is also related to dispersal. We studied natal dispersal (from rearing site to site of first breeding attempt) and breeding dispersal (from one breeding site to the next) in barn owls using a long-term data set. Darker reddish individuals moved further than paler individuals during natal dispersal, but not during breeding dispersal. A cross-fostering experiment showed that the colour of the biological and foster parents had no influence on dispersal distance. The distance dispersed by parents and same-sex offspring was correlated, whereas natal and breeding dispersal were not repeatable within individuals, indicating that they are two different processes. Given that the distance travelled in natal dispersal appears to be heritable, the underlying genes might be coupled to those related to coloration. We discuss hypotheses to explain the potential adaptive function of the link between coloration and natal dispersal.

Pre-hatching maternal effects inhibit nestling humoral immune response in the tawny owl Strix aluco

Although evidence is accumulating that mothers can transfer antibodies to their offspring, little is known about the consequences of such a transfer to the offspring immune system. Because maternal antibodies are effective only during a short period of time after their transfer to offspring, one hypothesis is that maternal antibodies provides a transitory antigen-specific protection to offspring, thus lessening the need for offspring to mount their own humoral immune response towards these specific antigens. In birds, this scenario predicts that offspring immune response towards a specific antigen is inhibited to a larger extent in hatchlings than in older nestlings. We tested this hypothesis in tawny owls Strix aluco by cross-fostering clutches between nests and then challenging siblings with a vaccine either two times (at 4- and 11-d-old) or only one time at 11-d-old to compare the strength of the humoral response between nestlings born from mothers with naturally high and low levels of antibodies against this vaccine. Because maternal antibodies are expected to be effective only during a short period of time after hatching, we predict that maternal antibodies should inhibit the immune response of nestlings vaccinated from the fourth day after hatching more than in nestlings vaccinated only at a later age. As expected, the inhibitory effect of maternal antibodies was stronger in nestlings vaccinated soon after hatching than in siblings injected at a later age. Therefore, in wild avian populations pre-hatching maternal effects may confer offspring with a transitory immune protection in the first days following hatching.

Endogenous constitutions

We present a theory of the choice of alternative democratic constitutions, a majoritarian or a consensual one, in an unequal society. A majoritarian democracy redistributes resources from the collectivity toward relatively few people, and has a relatively small government and low level of taxation. A consensual democracy redistributes resources toward a broader spectrum of social groups but also has a larger government and a higher level of taxation. We show that a consensual system turns out to be preferred by society when ex ante income inequality is relatively low, while a majoritarian system is chosen when income inequality is relatively high. We also obtain that consensual democracies should be expected to be ruled more often by center-left coalitions while the right should have an advantage in majoritarian constitutions. The implications for the relationship between inequality and redistribution are discussed. Historical evidence and a cross-sectional analysis support our results.

No consistent association between processes-of-care and health-related quality of life among patients with diabetes : a missing link?

PURPOSE: Health-related quality of life (HRQoL) is considered a representative outcome in the evaluation of chronic disease management initiatives emphasizing patient-centered care. We evaluated the association between receipt of processes-of-care (PoC) for diabetes and HRQoL. METHODS: This cross-sectional study used self-reported data from non-institutionalized adults with diabetes in a Swiss canton. Outcomes were the physical/mental composites of the short form health survey 12 (SF-12) physical composite score, mental composite score (PCS, MCS) and the Audit of Diabetes-Dependent Quality of Life (ADDQoL). Main exposure variables were receipt of six PoC for diabetes in the past 12 months, and the Patient Assessment of Chronic Illness Care (PACIC) score. We performed linear regressions to examine the association between PoC, PACIC and the three composites of HRQoL. RESULTS: Mean age of the 519 patients was 64.5 years (SD 11.3); 60% were male, 87% reported type 2 or undetermined diabetes and 48% had diabetes for over 10 years. Mean HRQoL scores were SF-12 PCS: 43.4 (SD 10.5), SF-12 MCS: 47.0 (SD 11.2) and ADDQoL: -1.6 (SD 1.6). In adjusted models including all six PoC simultaneously, receipt of influenza vaccine was associated with lower ADDQoL (β=-0.4, p≤0.01) and foot examination was negatively associated with SF-12 PCS (β=-1.8, p≤0.05). There was no association or trend towards a negative association when these PoC were reported as combined measures. PACIC score was associated only with the SF-12 MCS (β=1.6, p≤0.05). CONCLUSIONS: PoC for diabetes did not show a consistent association with HRQoL in a cross-sectional analysis. This may represent an effect lag time between time of process received and health-related quality of life. Further research is needed to study this complex phenomenon.

Physical activity in daily life is associated with lower adiposity values than doing weekly sports in Lc65+ cohort at baseline.

BACKGROUND: Overweight and obesity prevalence is the highest at age 65-75 years in Lausanne (compared with younger classes). We aimed to describe 1) eating habits, daily physical activity (PA), and sports frequency in community-dwelling adults aged 65-70, 2) the links of these behaviors with socio-economic factors, and 3) with adiposity. METHODS: Cross-sectional analysis of Lc65+ cohort at baseline, including 1260 adults from the general population of Lausanne aged 65-70 years. Eating habits (8 items from MNA) and PA (sports frequency and daily PA: walking and using stairs) were assessed by questionnaires. Body mass index (BMI), supra-iliac (SISF), triceps skin-folds (TSF), waist circumference (WC), and WHR were measured. RESULTS: Prevalence of overweight (BMI 25.0-29.9 kg/m2), obesity (BMI ≥ 30.0 kg/m2), and abdominal obesity was 53%, 24%, and 45% in men; 35%, 23%, and 45% in women.Intake of fruits or vegetables (FV) ≥ twice/day was negatively associated with male sex (prevalence 81% versus 90%, chi-square P < 0.001). The proportion avoiding stairs in daily life was higher among women (25%) than among men (20%, chi-square P=0.003).In multivariate analyses among both sexes, eating FV, using stairs in daily life ("stairs"), and doing sports ≥ once/week were significantly negatively associated with financial difficulties (stairs: OR=0.54, 95% CI=0.40-0.72) and positively with educational level (stairs: OR=1.68, 95% CI=1.17-2.43 for high school).For all five log-transformed adiposity indicators in women, and for all indicators except SISF and TSF in men, a gradual decrease in adiposity was observed from category "no stairs, sports < once/week" (reference), to "no stairs, sports ≥ once/week", to "stairs, sports < once/week", and "stairs, sports ≥ once/week" (for example: WC in men, respectively: ß= -0.03, 95% CI= -0.07-0.02; ß= -0.06, 95% CI= -0.09- -0.03; ß= -0.10, 95% CI= -0.12- -0.07). CONCLUSIONS: In this population with high overweight and obesity prevalence, eating FV and PA were strongly negatively associated with financial difficulties and positively with education. Using stairs in daily life was more strongly negatively associated with adiposity than doing sports ≥ once/week.

Experimental conversion of colony social organization in fire ants (Solenopsis invicta): worker genotype manipulation in absence of queen effects

Colony social organization in the fire ant Solenopsis invicta appears to be under strong genetic control. In the invasive USA range, polygyny (multiple queens per colony) is marked by the presence of the Gp-9(b) allele in most of a colony's workers, whereas monogyny (single queen per colony) is associated with the exclusive occurrence of the Gp-9(B) allele. Ross and Keller, Behav Ecol Sociobiol 51:287-295 (2002) experimentally manipulated social organization by cross-fostering queens into colonies of the alternate form, thereby changing adult worker Gp-9 genotype frequencies over time. Although these authors showed that social behavior switched predictably when the frequency of b-bearing adult workers crossed a threshold of 5-10%, the possibility that queen effects caused the conversions could not be excluded entirely. We addressed this problem by fostering polygyne brood into queenright monogyne colonies. All such treatment colonies switched social organization to become polygyne, coincident with their proportions of b-bearing workers exceeding 12%. Our results support the conclusion that polygyny in S. invicta is induced by a minimum frequency of colony workers carrying the b allele, and further confirm that its expression is independent of queen genotype or history, worker genotypes at genes not linked to Gp-9, and colony genetic diversity.