Defeatist Beliefs and Schizotypy in Adolescents and Emerging Adults

Defeatist beliefs involved overgeneralized negative beliefs regarding the ability to successfully perform tasks and accomplish goals. These cognitive errors have been shown to affect one’s ability to accurately assess and react in social situations and serve as hallmarks of many mood disorders. These negative beliefs also exist at high rates in adults with schizophrenia spectrum diagnoses. There is evidence for these beliefs existing during prodromal periods in young adults at-risk for psychosis, especially if they exhibit motivational or interpersonal difficulties (negative symptoms). However, there is little known about when these beliefs first emerge and whether they predate clinical disorder during earlier life stages where only subclinical presentations of risk (schizotypy) may be present. To address this research gap and help to inform cognitive-behavioral interventions targeting defeatist belief structures, we investigated the relations between defeatist beliefs and schizotypy in a sample of adolescents and emerging adults. Participants were 86 high school students (ages 14-17) and 270 college students (ages 18-22). Participants completed a 30-minute, self-report survey on defeatist beliefs and schizotypy. Our analyses found little difference in mean or standard deviation in defeatist beliefs or schizotypy between our two samples, with a robust positive association (r=0.46) when the samples where aggregated. These findings suggests that defeatist beliefs correspond with subclinical risk more-or-less on a continuum during this wider period of life potentially helping to understand variability in symptom severity. Future research is needed to clarify the nature of this relationship and to inform future interventions. Our finding suggests that cognitive behavioral approaches, which are well suited to target and modify defeatist beliefs, could serve a preventative role in the risk for future psychosis in at-risk adolescents and emerging adults

Comprehensive methylome map of lineage commitment from haematopoietic progenitors.

Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions

Educational outreach to general practitioners reduces children's asthma symptoms: a cluster randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Childhood asthma is common in Cape Town, a province of South Africa, but is underdiagnosed by general practitioners. Medications are often prescribed inappropriately, and care is episodic. The objective of this study is to assess the impact of educational outreach to general practitioners on asthma symptoms of children in their practice.</p> <p>Methods</p> <p>This is a cluster randomised trial with general practices as the unit of intervention, randomisation, and analysis. The setting is Mitchells Plain (population 300,000), a dormitory town near Cape Town. Solo general practitioners, without nurse support, operate from storefront practices. Caregiver-reported symptom data were collected for 318 eligible children (2 to 17 years) with moderate to severe asthma, who were attending general practitioners in Mitchells Plain. One year post-intervention follow-up data were collected for 271 (85%) of these children in all 43 practices.</p> <p>Practices randomised to intervention (21) received two 30-minute educational outreach visits by a trained pharmacist who left materials describing key interventions to improve asthma care. Intervention and control practices received the national childhood asthma guideline. Asthma severity was measured in a parent-completed survey administered through schools using a symptom frequency and severity scale. We compared intervention and control group children on the change in score from pre-to one-year post-intervention.</p> <p>Results</p> <p>Symptom scores declined an additional 0.84 points in the intervention vs. control group (on a nine-point scale. p = 0.03). For every 12 children with asthma exposed to a doctor allocated to the intervention, one extra child will have substantially reduced symptoms.</p> <p>Conclusion</p> <p>Educational outreach was accepted by general practitioners and was effective. It could be applied to other health care quality problems in this setting.</p

Iteration functions re-visited

Two classes of Iteration Functions (IFs) are derived in this paper. The first (one-point IFs) was originally derived by Joseph Traub using a different approach to ours (simultaneous IFs). The second is new and is demonstrably shown to be more informationally efficient than the first. These IFs apply to polynomials with arbitrary complex coefficients and zeros, which can also be multiple

Dietary Composition Modulates Brain Mass and Solubilizable ABeta Levels in a Mouse Model of Aggressive Alzheimer\u27s Amyloid Pathology

Objective: Alzheimer\u27s disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods: From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable Aβ content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions. Results: Animals receiving a high fat diet showed increased brain levels of solubilizable Aβ, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus. Interpretation: Dissociation of Aβ changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology

Future Generations: economic, legal and institutional aspects

In economics, the issue of ‘future generations’ is mainly related to the environmental problems of resource consumption and pollution and their distribution over long time horizons. This paper critically discusses fundamental concepts in economics, such as efficiency and optimality, in relation to the incorporation of future generations in present day decision-making. Cost–benefit analysis (CBA) and discounting are used as a starting point and criticized for its inherent flaws such as incommensurability of values and its tendency to hide rather than reveal underlying values which are assumed to be fixed. We then investigate alternative approaches, in which, unlike in CBA, the preferences are not assumed to be a priori but must be constructed. Thus, interest groups or individuals must sit down together and figure out what things seem to be worth. The aim is to involve all interested parties in planning for the future. Similarly, on a national and regional level, increasingly stakeholder processes, deliberative and interest group procedures are used to develop strategies and visions for resource management and conservation. A similar case can be made for institutions at the international level. The legal examples provided in this paper show that rather than only installing an institution such as the guardian for the future on the global level, more ‘democratized’ bottom up approaches might be more appropriate