Normal values for pancreatic stone protein in different age groups.

BACKGROUND Pancreatic stone protein (PSP) has been identified as a promising sepsis marker in adults, children and neonates. However, data on population-based reference values are lacking. This study aimed to establish age-specific reference values for PSP. METHODS PSP was determined using a specific ELISA. PSP serum concentrations were determined in 372 healthy subjects including 217 neonates, 94 infants and children up to 16 years, and 61 adults. The adjacent categories method was used to determine which age categories had significantly different PSP concentrations. RESULTS PSP circulating levels were not gender-dependent and ranged from 1.0 to 99.4 ng/ml with a median of 9.2 ng/ml. PSP increased significantly between the age categories, from a median of 2.6 ng/ml in very preterm newborns, to 6.3 ng/ml in term newborns, to 16.1 ng/ml in older children (p < 0.001). PSP levels were higher on postnatal day three compared to levels measured immediately post delivery (p < 0.001). Paired umbilical artery and umbilical vein samples were strongly correlated (p < 0.001). Simultaneously obtained capillary heel-prick versus venous samples showed a good level of agreement for PSP (Rho 0.89, bias 19 %). CONCLUSIONS This study provides age-specific normal values that may be used to define cut-offs for future trials on PSP. We demonstrate an age-dependent increase of PSP from birth to childhood.

Cognitive rehabilitation of working memory in juvenile multiple sclerosis-effects on cognitive functioning, functional MRI and network related connectivity.

PURPOSE To assess possible effects of working memory (WM) training on cognitive functionality, functional MRI and brain connectivity in patients with juvenile MS. METHODS Cognitive status, fMRI and inter-network connectivity were assessed in 5 cases with juvenile MS aged between 12 and 18 years. Afterwards they received a computerized WM training for four weeks. Primary cognitive outcome measures were WM (visual and verbal) and alertness. Activation patterns related to WM were assessed during fMRI using an N-Back task with increasing difficulty. Inter-network connectivity analyses were focused on fronto-parietal (left and right), default-mode (dorsal and ventral) and the anterior salience network. Cognitive functioning, fMRI and inter-network connectivity were reassessed directly after the training and again nine months following training. RESULTS Response to treatment was seen in two patients. These patients showed increased performance in WM and alertness after the training. These behavioural changes were accompanied by increased WM network activation and systematic changes in inter-network connectivity. The remaining participants were non-responders to treatment. Effects on cognitive performance were maintained up to nine months after training, whereas effects observed by fMRI disappeared. CONCLUSIONS Responders revealed training effects on all applied outcome measures. Disease activity and general intelligence may be factors associated with response to treatment.

Innovation and Development in the Age of Climate Change Adaptation: Open or Closed?

Change Adaptation: Open or Closed? Paper read at the Second African International Economic Law Network Conference, 7-8 March 2013, Wits School of Law, Johannesburg, South Africa. In a time of rapid convergence of technologies, goods, services, hardware, software, the traditional classifications that informed past treaties fail to remove legal uncertainty, or advance welfare and innovation. As a result, we turn our attention to the role and needs of the public domain at the interface of existing intellectual property rights and new modes of creation, production and distribution of goods and services. The concept of open culture would have it that knowledge should be spread freely and its growth should come from further developing existing works on the basis of sharing and collaboration without the shackles of intellectual property. Intellectual property clauses find their way into regional, multilateral, bilateral and free trade agreements more often than not, and can cause public discontent and incite unrest. Many of these intellectual property clauses raise the bar on protection beyond the clauses found in the WTO Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). In this paper we address the question of the protection and development of the public domain in service of open innovation in accord with Article 15 of the International Covenant on Economic, Social and Cultural Rights (ICESCR) in light of the Objectives (Article 7) and Principles (Article 8) set forth in TRIPS. Once areas of divergence and reinforcement between the intellectual property regime and human rights have been discussed, we will enter into options that allow for innovation and prosperity in the global south. We then conclude by discussing possible policy developments.

Dementia with lewy bodies--diagnosis and treatment

Dementia with Lewy bodies (DLB) accounts for 15-20% of all autopsy confirmed dementias in old age. Characteristic histopathological changes are intracellular Lewy bodies and Lewy neurites, with abundant senile plaques but sparse neurofibrillary tangles. Core clinical features are fluctuating cognitive impairment, persistent visual hallucinations and extrapyramidal motor symptoms (parkinsonism). One of these core features has to be present for a diagnosis of possible DLB, and two for probable DLB. Supportive features are repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, delusions and hallucinations in other modalities. DLB is clinically under-diagnosed and frequently misclassified as systemic delirium or dementia due to Alzheimer's disease or cerebrovascular disease. Therapeutic approaches to DLB can pose difficult dilemmas in pharmacological management. Neuroleptic medication is relatively contraindicated because some patients show severe neuroleptic sensitivity, which is associated with increased morbidity and mortality. Antiparkinsonian medication has the potential to exacerbate psychotic symptoms and may be relatively ineffective at relieving extrapyramidal motor symptoms. Recently there is converging evidence that treatment with cholinesterase inhibitors can offer a safe alternative for the symptomatic treatment of cognitive and neuropsychiatric features in DLB. This review will focus on the clinical characteristics of DLB, its differential diagnosis and on possible management strategies.

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.

Self-esteem development across the life span: A longitudinal study with a large sample from Germany

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the life span, increasing during adolescence, young adulthood, and middle adulthood, reaching a peak at age 60 years, and then declining in old age. No cohort effects on average levels of self-esteem or on the shape of the trajectory were found. Moreover, the trajectory did not differ across gender, level of education, or for individuals who had lived continuously in West versus East Germany (i.e., the 2 parts of Germany that had been separate states from 1949 to 1990). However, the results suggested that employment status, household income, and satisfaction in the domains of work, relationships, and health contribute to a more positive life span trajectory of self-esteem. The findings have significant implications, because they call attention to developmental stages in which individuals may be vulnerable because of low self-esteem (such as adolescence and old age) and to factors that predict successful versus problematic developmental trajectories.

Life-span development of self-esteem and its effects on important life outcomes

We examined the life-span development of self-esteem and tested whether self-esteem influences the development of important life outcomes, including relationship satisfaction, job satisfaction, occupational status, salary, positive and negative affect, depression, and physical health. Data came from the Longitudinal Study of Generations. Analyses were based on 5 assessments across a 12-year period of a sample of 1,824 individuals ages 16 to 97 years. First, growth curve analyses indicated that self-esteem increases from adolescence to middle adulthood, reaches a peak at about age 50 years, and then decreases in old age. Second, cross-lagged regression analyses indicated that self-esteem is best modeled as a cause rather than a consequence of life outcomes. Third, growth curve analyses, with self-esteem as a time-varying covariate, suggested that self-esteem has medium-sized effects on life-span trajectories of affect and depression, small to medium-sized effects on trajectories of relationship and job satisfaction, a very small effect on the trajectory of health, and no effect on the trajectory of occupational status. These findings replicated across 4 generations of participants— children, parents, grandparents, and their great-grandparents. Together, the results suggest that self-esteem has a significant prospective impact on real-world life experiences and that high and low self-esteem are not mere epiphenomena of success and failure in important life domains.

Tracking the trajectory of shame, guilt, and pride across the life span

The authors examined age differences in shame, guilt, and 2 forms of pride (authentic and hubristic) from age 13 years to age 89 years, using cross-sectional data from 2,611 individuals. Shame decreased from adolescence into middle adulthood, reaching a nadir around age 50 years, and then increased in old age. Guilt increased from adolescence into old age, reaching a plateau at about age 70 years. Authentic pride increased from adolescence into old age, whereas hubristic pride decreased from adolescence into middle adulthood, reaching a minimum around age 65 years, and then increased in old age. On average, women reported experiencing more shame and guilt; Blacks reported experiencing less shame and Asians more hubristic pride than other ethnicities. Across the life span, shame and hubristic pride tended to be negatively related to psychological well-being, and shame-free guilt and authentic pride showed positive relations with well-being. Overall, the findings support the maturity principle of personality development and suggest that as people age they become more prone to experiencing psychologically adaptive self-conscious emotions, such as guilt and authentic pride, and less prone to experiencing psychologically maladaptive ones, such as shame and hubristic pride.

β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis

Aging drives cognitive and regenerative impairments in the adult brain, increasing susceptibility to neurodegenerative disorders in healthy individuals. Experiments using heterochronic parabiosis, in which the circulatory systems of young and old animals are joined, indicate that circulating pro-aging factors in old blood drive aging phenotypes in the brain. Here we identify β2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. B2M is elevated in the blood of aging humans and mice, and it is increased within the hippocampus of aged mice and young heterochronic parabionts. Exogenous B2M injected systemically, or locally in the hippocampus, impairs hippocampal-dependent cognitive function and neurogenesis in young mice. The negative effects of B2M and heterochronic parabiosis are, in part, mitigated in the hippocampus of young transporter associated with antigen processing 1 (Tap1)-deficient mice with reduced cell surface expression of MHC I. The absence of endogenous B2M expression abrogates age-related cognitive decline and enhances neurogenesis in aged mice. Our data indicate that systemic B2M accumulation in aging blood promotes age-related cognitive dysfunction and impairs neurogenesis, in part via MHC I, suggesting that B2M may be targeted therapeutically in old age.

Ten-year comparison of pericardial tissue valves versus mechanical prostheses for aortic valve replacement in patients younger than 60 years of age

Aortic valve replacement using a tissue valve is controversial for patients younger than 60 years old. The long-term survival in this age group, the expected event rates during long-term follow-up, and valve-related complications are not clearly determined.