Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes

Telomerase activity is readily detectable in extracts from human hematopoietic stem and progenitor cells, but appears unable to maintain telomere length with proliferation in vitro and with age in vivo. We performed a detailed study of the telomere length by flow FISH analysis in leukocytes from 835 healthy individuals and 60 individuals with reduced telomerase activity. Healthy individuals showed a broad range in average telomere length in granulocytes and lymphocytes at any given age. The average telomere length declined with age at a rate that differed between age-specific breakpoints and between cell types. Gender differences between leukocyte telomere lengths were observed for all cell subsets studied; interestingly, this trend could already be detected at birth. Heterozygous carriers for mutations in either the telomerase reverse transcriptase (hTERT) or the telomerase RNA template (hTERC) gene displayed striking and comparable telomere length deficits. Further, non-carrier relatives of such heterozygous individuals had somewhat shorter leukocyte telomere lengths than expected; this difference was most profound for granulocytes. Failure to maintain telomere homeostasis as a result of partial telomerase deficiency is thought to trigger cell senescence or cell death, eventually causing tissue failure syndromes. Our data are consistent with these statements and suggest that the likelihood of similar processes occurring in normal individuals increases with age. Our work highlights the essential role of telomerase in the hematopoietic system and supports the notion that telomerase levels in hematopoietic cells, while limiting and unable to prevent overall telomere shortening, are nevertheless crucial to maintain telomere homeostasis with age.

The KIDSCREEN-27 quality of life measure for children and adolescents: psychometric results from a cross-cultural survey in 13 European countries

OBJECTIVE: To assess the construct and criterion validity of the KIDSCREEN-27 health-related quality of life (HRQoL) questionnaire, a shorter version of the KIDSCREEN-52. METHODS: The five-dimensional KIDSCREEN-27 was tested in a sample of 22,827. For criterion validity the correlation with and the percentage explained variance of the scores of the KIDSCREEN-52 instrument were examined. Construct validity was assessed by testing a priori expected associations with other generic HRQoL measures (YQOL-S, PedsQL, CHIP), indicators of physical and mental health, and socioeconomic status. Age and gender differences were investigated. RESULTS: Correlation with corresponding scales of the KIDSCREEN-52 ranged from r = 0.63 to r = 0.96, and r2 ranged from 0.39 to 0.92. Correlations between other HRQoL questionnaires and KIDSCREEN-27 dimensions were moderate to high for those assessing similar constructs (r = 0.36 to 0.63). Statistically significant and sizeable differences between physically and mentally healthy and ill children were found in all KIDSCREEN-27 dimensions together with strong associations with psychosomatic complaints (r = -0.52). Most of the KIDSCREEN-27 dimensions showed a gradient according to socio-economic status, age and gender. CONCLUSIONS: The KIDSCREEN-27 seems to be a valid measure of HRQoL in children and adolescents. Further research is needed to assess longitudinal validity and sensitivity to change.

Assessment of vertical facial and dentoalveolar changes using panoramic radiography

The purpose of the study was to analyse longitudinal vertical facial and dentoalveolar changes using panoramic radiographs (PRs) and to compare the results with measurements on lateral cephalometric radiographs (LCRs) in order to determine whether, under certain circumstances, the radiation dose for a patient may be reduced by taking only a PR instead of a PR and a LCR. Pre- and post-treatment PRs and LCRs of 30 (15 females and 15 males) orthodontically treated adolescents (mean age pre-treatment 10.9 years, post-treatment 13.4 years) were analysed using Pearson's correlation coefficients and gender differences using Fisher's z-transformation. The results revealed that most variables exhibited larger absolute values on PRs than on LCRs. Comparison of dentoskeletal morphology between the LCRs and the PRs revealed moderate to high, mostly statistically significant, interrelations both before and after orthodontic treatment. The lowest correlations were found for the maxillary jaw base angle (NL/H; r= 0.35***) and the highest for the gonial angle (ML/RL; r = 0.90***). However, when assessing the combined growth and treatment changes from before to after treatment, only weak to moderate, not statistically significant, interrelations were found between LCRs and PRs. Anterior face height (AFH; r = 0.43***), the mandibular plane angle (ML/H; r = 0.06*), and the distance of the incisal tip of the most extruded mandibular incisor to the ML-line (ii-ML; r = -0.21*) were the only statistically significant parameters. The average group differences for growth and treatment changes, however, were small for most parameters. Analysis of vertical facial and dentoalveolar parameters on PRs delivers a moderate approximation to the situation depicted on LCRs. However, PRs cannot be recommended for the analysis of individual longitudinal changes in vertical facial and dentoalveolar parameters.

Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index

OBJECTIVE: Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta-analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub-site and study characteristics. METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. Random-effects meta-analyses and meta-regressions of study-specific incremental estimates were performed to determine the risk ratio (RR) and 95% confidence intervals (CIs) associated with a 5 kg/m(2) increase in BMI. RESULTS: We analysed 29 datasets from 28 articles, including 67,361 incident cases. Higher BMI was associated with colon (RR 1.24, 95% CIs: 1.20-1.28) and rectal (1.09, 1.05-1.14) cancers in men, and with colon cancer (1.09, 1.04-1.12) in women. Associations were stronger in men than in women for colon (P < 0.001) and rectal (P = 0.005) cancers. Associations were generally consistent across geographic populations. Study characteristics and adjustments accounted for only moderate variations of associations. CONCLUSION: Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic differences, which merit further research.

Expected and Unexpected Consequences of the Educational Expansion in Europe and the US. Theoretical approaches and empirical findings in comparative perspective

A main mechanism behind the change in European and North American societies in the second half of the 20th century is the educational expansion, i.e. the increase in educational opportunities and the higher demand for education. Whereas other abstract social processes like modernization have been widely theorized in social science literature, the educational expansion and its consequences in particular have not been well studied. Therefore the main aim of this compilation is to deal with the question of whether the demands of the educational reforms have been fulfilled and which other consequences the educational expansion has had. This book will focus on consequences of the educational expansion for individuals and their life courses as well as for the social structure and other societal areas such as culture and politics. Aspects that will be analysed in the light of educational expansion include participation in education, educational inequalities, labour market outcomes, educational returns, and gender differences as well as crime, life expectancy, and lifestyles. Countries analysed in the book include West European countries like Germany, France, Italy and Spain, East European countries (Hungary, Poland, and the Czech Republic) as well as the US.

Development of Values after Compulsory School: Work comes first, then family

During school-to-work transition, adolescents develop values and prioritize what is im-portant in their life. Values are concepts or beliefs about desirable states or behaviors that guide the selection or evaluation of behavior and events, and are ordered by their relative importance (Schwartz & Bilsky, 1987). Stressing the important role of values, career re-search has intensively studied the effect of values on educational decisions and early career development (e.g. Eccles, 2005; Hirschi, 2010; Rimann, Udris, & Weiss, 2000). Few re-searchers, however, have investigated so far how values develop in the early career phase and how value trajectories are influenced by individual characteristics. Values can be oriented towards specific life domains, such as work or family. Work values include intrinsic and extrinsic aspects of work (e.g., self-development, cooperation with others, income) (George & Jones, 1997). Family values include the importance of partner-ship, the creation of an own family and having children (Mayer, Kuramschew, & Trommsdroff, 2009). Research indicates that work values change considerably during early career development (Johnson, 2001; Lindsay & Knox, 1984). Individual differences in work values and value trajectories are found e.g., in relation to gender (Duffy & Sedlacek, 2007), parental background (Loughlin & Barling, 2001), personality (Lowry et al., 2012), educa-tion (Battle, 2003), and the anticipated timing of school-to-work transition (Porfeli, 2007). In contrast to work values, research on family value trajectories is rare and knowledge about the development during the school-to-work transition and early career development is lack-ing. This paper aims at filling this research gap. Focusing on family values and intrinsic work values and we expect a) family and work val-ues to change between ages 16 and 25, and b) that initial levels of family and work values as well as value change to be predicted by gender, reading literacy, ambition, and expected du-ration of education. Method. Using data from 2620 young adults (59.5% females), who participated in the Swiss longitudinal study TREE, latent growth modeling was employed to estimate the initial level and growth rate per year for work and family values. Analyses are based on TREE-waves 1 (year 2001, first year after compulsory school) to 8 (year 2010). Variables in the models included family values and intrinsic work values, gender, reading literacy, ambition and ex-pected duration of education. Language region was included as control variable. Results. Family values did not change significantly over the first four years after leaving compulsory school (mean slope = -.03, p =.36). They increased, however, significantly five years after compulsory school (mean slope = .13, p >.001). Intercept (.23, p < .001), first slope (.02, p < .001), and second slope (.01, p < .001) showed significant variance. Initial levels were higher for men and those with higher ambitions. Increases were found to be steeper for males as well as for participants with lower educational duration expectations and reading skills. Intrinsic work values increased over the first four years (mean slope =.03, p <.05) and showed a tendency to decrease in the years five to ten (mean slope = -.01, p < .10). Intercept (.21, p < .001), first slope (.01, p < .001), and second slope (.01, p < .001) showed signifi-cant variance, meaning that there are individual differences in initial levels and growth rates. Initial levels were higher for females, and those with higher ambitions, expecting longer educational pathways, and having lower reading skills. Growth rates were lower for the first phase and steeper for the second phase for males compared to females. Discussion. In general, results showed different patterns of work and family value trajecto-ries, and different individual factors related to initial levels and development after compul-sory school. Developments seem to fit to major life and career roles: in the first years after compulsory school young adults may be engaged to become established in one's job; later on, raising a family becomes more important. That we found significant gender differences in work and family trajectories may reflect attempts to overcome traditional roles, as over-all, women increase in work values and men increase in family values, resulting in an over-all trend to converge.

Personality factors in elementary school children: Contributions to academic performance over and above executive functions?

Unique contributions of Big Five personality factors to academic performance in young elementary school children were explored. Extraversion and Openness (labeled “Culture” in our study) uniquely contributed to academic performance, over and above the contribution of executive functions in first and second grade children (N = 446). Well established associations between Conscientiousness and academic performance, however, could only be replicated with regard to zero-order correlations. Executive functions (inhibition, updating, and shifting), for their part, proved to be powerful predictors of academic performance. Results were to some extent dependent on the criterion with which academic performance was measured: Both personality factors had stronger effects on grades than on standardized achievement tests, whereas the opposite was true for executive functions. Finally, analyses on gender differences revealed that Extraversion and Openness/Culture played a more dominant role in girls than in boys, but only regarding grades.

What do we mean by Female and Male in Neurocognitive Experiments on Language?

For several years now, neuroscientific research has been striving towards fundamental answers to questions about the relevance of sex/gender to language processing in the brain. This research has been effected through the search for sex/gender differences in the neurobiology of language processing. Thus, the main aim has ever been to focus on the differentiation of the sexes/genders, failing to define what sex, what gender, what female or male is in neurolingustic research. In other words, although neuroscientific findings have provided key insights into the brain functioning of women and men, neuropsychology has rarely questioned the complexity of the sex/gender variable beyond biology. What does “female” or “male” mean in human neurocognition; how are operationalisations implemented along the axes of “femaleness” or “maleness”; or what biological evidence is used to register the variables sex and/or gender? In the neurosciences as well as in neurocognitive research, questions such as these have so far not been studied in detail, even if they are highly significant for the scientific process. Instead, the variable of sex/gender has always been thought as solely dichotomous (as either female or male), oppositional and exclusionary of each other. Here, this theoretical contribution sets in. Based on findings in neuroscience and concepts in gender theory, this poster is dedicated to the reflection about what sex/gender is in the neuroscience of language processing. Following this aim, two levels of interest will be addressed. First: How do we define sex/gender at the level of participants? And second: How do we define sex/gender at the level of the experimental task? For the first, a multifactorial registration (work in progress) of the variable sex/gender will be presented, i.e. a tool that records sex/gender in terms of biology and social issues as well as on a spectrum between femaleness and maleness. For the second, the compulsory dichotomy of a gendered task when neurolinguistically approaching our cognitions of sex/gender will be explored.

Does body mass index in childhood predict restraint eating in early adolescence?

The aim of this study was (1) to examine whether childhood BMI is a significant predictor of restrained eating in preadolescents, (2) to investigate gender differences in restrained and emotional eating, and (3) to determine whether emotional problems, and body esteem were related to eating problems of preadolescents. In this longitudinal study with two measurement points, data from 428 children (50% female) were used. At time 1 (t1) children were on average 5.9 years old. BMI was assessed using objective measures. At time 2 (t2) participants were 12 years old. The adolescents and their parents completed questionnaires assessing restrained and emotional eating, body esteem, emotional problems, and BMI. Multiple regression analysis showed that restrained eating was significantly predicted by t1 BMI, by change in BMI between t1 and t2, and t2 body esteem. Emotional eating was, as expected, not predicted by t1 BMI, but associated with t2 body esteem and t2 emotional problems. Gender was not a significant predictor. The stability of BMI between childhood and preadolescence and its ability to predict restrained eating suggests that it is important to start prevention of overweight, body dissatisfaction and disordered eating at an early age

Selenium for preventing cancer

BACKGROUND This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Riding the Escalator: How Dangerous is it Really?

INTRODUCTION About 10,000 escalator-related injuries per year result in emergency department treatment in the United States. Since the 1990s, a steady increase has been reported, but few statistics on escalator-related injuries have been published worldwide. We have therefore analyzed escalator accident statistics in admissions to our hospital in Switzerland since 2000. METHODS Using retrospective electronic patient chart analysis, we included in our study patients >16 years treated over an 11-year period. We categorized patients in terms of gender, age and associated risk factors, and classified accidents according to day, time, location and cause. Resulting trauma was categorized according to type and location. We divided post-admission treatment into surgical and conservative, and into treatment as an outpatient, in a short-stay unit, or as a hospital admission. Women and men were compared using Fisher's exact test. RESULTS We identified 173 patients with 285 discrete injuries. Of these, 87 patients (50%) were women. Fifty-three (61%) of the women and 38 (44%) of the men were >60 years old (P = 0.033). Fifty percent of the men (43/86) of the men, but only 7% (6/87) of the women showed signs of alcohol intoxication (P < 0.0001). Accidents in women occurred predominantly on Tuesdays (19/87; 22%) between 12pm and 6pm (35/87; 40%), and in men on Saturdays (16/86; 19%) between 6pm and 12am (29/86; 34%; P = 0.0097). Sixty-two percent (44/71) of the accidents were in public transport facilities and 30% (21/71) in shopping centers. The majority of injuries in women were to the lower extremities (49/87; 56%), while most accidents in men were to the head and neck (51/86; 59%; P = 0.0052). About half (90; 52%) of the patients were treated conservatively. Almost half of all patients (76, 44%) required hospital admission. Of those, 45% left the hospital within 24 hours of admission (short stay unit) and 55% stayed longer than 24 hours. CONCLUSION Escalator accidents can result in severe trauma. Significant gender differences in escalator accidents have been observed. Alcohol intoxication and age are significant risk factors in escalator-related accidents and might be possible targets for preventive measures.

Differential aspects of memory self-evaluation in old and very old people

The aim of this paper was to examine age-related changes and gender differences in memory self-evaluation in old people and to examine the predictive power of objective memory performance and of personality variables (neuroticism and extraversion) on memory self-evaluation. In a cross-sectional study, 301 not institutionalized people aged 65± 94, 207 male and 94 female, were tested on three parameters. Subjective memory evaluation was operationalized with three one-item ratings: temporal comparison, social comparison, situation-speci® c memory self-evaluation just after performing a memory test. Objective memory assessment (free recall) used a computerized test. Personality assessment included the two main sub-scales `extraversion’ and `neuroticism’ from the Freiburger PersoÈ nlichkeits-Inventar.The results shaved that persons of all age groups have a realistic appraisal of their age-related memory decline.No gender effects were found for any of the three forms of memory self-evaluation. The relationship between objective memory performance, personality variables and memory self-evaluation however depends on age and gender. Our results show that objective memory performance is predictive for memory self-evaluation in men aged >75 years, whereas in men <75 neuroticism is the only signi® cant predictor.Men of the older cohort seem to have adapted to the age-related memory decline whereas the young old are still coping with the ongoing changes. In women of both age groups the objective memory performance is the only and strong predictor of memory self-evaluation. Our results suggest that gender-speci® c educational socialization might be the reason for these differences.

Persönliche Bilanzierung der Herausforderungen einer Verwitwung im Zeit- und Geschlechtervergleich

Bisherige Forschung hat die Verwitwung entweder primär als soziales oder als individuelles Ereignis untersucht, selten jedoch wurden beide Perspektiven verbunden. Zudem ist wenig darüber bekannt, inwiefern bisherige Forschungsergebnisse Perioden- oder Kohorteneffekte wiederspiegeln. In diesem Beitrag wird die persönliche Bilanzierung nach der Verwitwung älterer Schweizer Frauen und Männer im Geschlechterund Zeitvergleich untersucht1. Die Datenbasis beruht auf Befragungen von 1.197 verwitweten Frauen und Männern (Alter: 65-102 Jahre), welche 1979, 1994 und 2011 durchgeführt wurden. Während sich die wirtschaftlichen und sozialen Rahmenbedingungen nach einer Verwitwung – namentlich bei Frauen – im Zeitvergleich verbessert haben, zeigen sich bezüglich psychischer Herausforderungen einer Verwitwung keine periodenspezifischen Veränderungen. Psychisch bleibt der Partnerverlust auch bei günstigen Sozialbedingungen ein kritisches Lebensereignis, das individualisiert bewältigt werden muss.

Motor ability and self-esteem: The mediating role of physical self-concept and perceived social acceptance

Objectives: One important issue in sport and exercise psychology is to determine to what extent sports and exercise can help to increase self-esteem, and what the underlying mechanism might be. Based on the exercise and self-esteem model (EXSEM) and on findings from the sociometer theory, the mediating effect of physical self-concept and perceived social acceptance on the longitudinal relationship between motor ability and self-esteem was investigated. Design: Longitudinal study with three waves of data collection at intervals of ten weeks each. Method: 428 adolescents (46.3 % girls, mean age = 11.9, SD = .55) participated in the study, in which they performed three motor ability tests and completed paper-and-pencil questionnaires for physical self-concept and perceived social acceptance, as well as for self-esteem, at all three measuring points. Results: Using structural equation modelling procedures, the multiple mediation model revealed both physical self-concept and perceived social acceptance to be mediators between motor ability and self-esteem in the case of boys. In girls, on the other hand, the mediation between motor ability and self-esteem only takes place via physical self-concept. Conclusions: Gender differences in the relationship between motor ability and self-esteem suggest gender-specific interventions aimed at promoting self-concept.

Eine typologische Analyse des schweizerischen Lehrstellenmarktes: Strukturelle Benachteiligung von jungen Frauen

Empirische Studien zeigen, dass junge Frauen in der Schweiz mehr Mühe in der Lehrstellensuche bekunden als Männer. Die Studie überprüft die Hypothesen, dass dies auch in einem geringeren Angebot an Lehrberufen und Lehrstellen sowie tendenziell höheren schulischen Anforderungen in ihren typischen Interessensbereichen im Vergleich zu den typischen Interessensbereichen von Männern begründet liegt. Dazu wird eine typologische Analyse des Schweizer Lehrstellenmarktes 2006 aufgrund der RIASEC Typologie von Holland (1997) vorgenommen und in direkten Bezug zur gut fundierten beruflichen Interessenforschung gestellt. Beide Hypothesen wurden bestätigt. Implikationen für Theorie und Praxis werden beschrieben.