Migraine with aura and migraine without aura are not distinct entities: further evidence from a large Dutch population study

It is often debated whether migraine with aura (MA) and migraine without aura (MO) are etiologically distinct disorders. A previous study using latent class analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO and MA. The aim of the present study was to replicate these results in a population of Dutch twins and their parents, siblings and partners (N = 10,144). Latent class analysis of International Headache Society (IHS)-based migraine symptoms resulted in the identification of 4 classes: a class of unaffected subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately severe type of migraine (class 2), typically without neurological symptoms or aura (8% reporting aura symptoms), and a severe type of migraine (class 3), typically with neurological symptoms, and aura symptoms in approximately half of the cases. Given the overlap of neurological symptoms and nonmutual exclusivity of aura symptoms, these results do not support the MO and MA subtypes as being etiologically distinct. The heritability in female twins of migraine based on LCA classification was estimated at .50 (95% confidence intervals [CI] .27 - .59), similar to IHS-based migraine diagnosis (h2 = .49, 95% CI .19-.57). However, using a dichotomous classification (affected-unaffected) decreased heritability for the IHS-based classification (h2 = .33, 95% CI .00-.60), but not the LCA-based classification (h2 = .51, 95% CI .23-.61). Importantly, use of the LCA-based classification increased the number of subjects classified as affected. The heritability of the screening question was similar to more detailed LCA and IHS classifications, suggesting that the screening procedure is an important determining factor in genetic studies of migraine.

Effects of self-reported wisdom on happiness: Not much more than emotional intelligence?

Wisdom and emotional intelligence are increasingly popular topics among happiness scholars. Despite their conceptual overlap, no empirical research has examined their interrelations and incremental predictive validities. The aims of this study were (a) to investigate associations between multidimensional conceptualizations of self-reported wisdom (Ardelt in Res Aging 25(3):275-324, 2003, 2004) and emotional intelligence (Davies et al. in J Pers Soc Psychol 75:989-1015, 1998) and (b) to examine the joint effects of self-reported wisdom and emotional intelligence on dimensions of happiness (life satisfaction as well as positive and negative affect). Data were provided by two samples: 175 university students and 400 online workers. Correlations between a composite wisdom score, a composite emotional intelligence score, and happiness facets were positive and moderate in size. Regression analyses showed that the effects of composite wisdom on life satisfaction and positive affect (but not negative affect) became weaker and non-significant when composite emotional intelligence was controlled. Additional analyses including three dimensions of the self-reported wisdom (cognitive, reflective, and affective wisdom) and four dimensions of emotional intelligence (self- and others-emotions appraisal, use and regulation of emotion) revealed a more differentiated pattern of results. Implications for future research on wisdom and happiness are discussed.

The evolution of entrepreneurial learning

- Purpose The purpose of this paper is to present an evolutionary perspective on entrepreneurial learning, whilst also accounting for fundamental ecological processes, by focusing on the development of key recurring, knowledge components within nascent and growing small businesses. - Design/methodology/approach The paper relates key developments within the organizational evolution literature to research on entrepreneurial learning, with arguments presented in favor of adopting a multi‐level co‐evolutionary perspective that captures and explains hidden ecological process, such as niche‐construction. - Findings It is argued in the paper that such a multi‐level focus on key recurring knowledge components can shed new light on the process of entrepreneurial learning and lead to the cross‐fertilization of ideas across different domains of study, by offering researchers the opportunity to use the framework of variation‐selection‐retention to develop a multi‐level representation of organizational and entrepreneurial learning. - Originality/value Entrepreneurial learning viewed in this way, as a multi‐level struggle for survival amongst competing knowledge components, can provide entrepreneurs with a set of evolutionary heuristics as they re‐interpret their understanding of the evolution of their business.

Creating the reasonable adventurer: The co-evolution of student and learning environment

Purpose: This paper seeks to address the issue of how are graduate skills developed. The focus is not on which skills, but rather what type of learning environments is required within Higher Education to support the development of skills valued and demanded by SMEs within Australia. Approach: This paper takes a step back to consider the underlying issue of how an individual student's habits of thought are altered. In doing so, the past works of Morgan, Dewey, Whitehead, and Tyler are synthesized with the modern work of Baxter Magolda, Heath, and Biggs. Findings: It is argued that that without the development of a student-centred learning environment, most graduates will not develop the types of skills demanded by SMEs in a meaningfully way. That the failure to treat knowledge and skills as equal drivers of curriculum design will result in an imbalance that relegates skill development to a secondary learning outcome. Practical Implications: By removing the distraction of what skills should be developed, a clearer focus is possible regarding how educators should assist students to develop a broad array of generic graduate skills. From this perspective, skills can be viewed as an essential element of the educational process, rather than a new element that must be squeezed in between content. Value of Paper: This paper extends recent discussion of skills development through the use of an evolutionary perspective. Viewed as a process of creating social change, education becomes increasingly connected to a world that lays beyond institutional boundaries, thus promoting the notion of developing graduates for the world that awaits them.

Cell surface heparan sulfate proteoglycans as novel markers of human neural stem cell fate determination

Multipotent neural stem cells (NSCs) provide a model to investigate neurogenesis and develop mechanisms of cell transplantation. In order to define improved markers of stemness and lineage specificity, we examined self-renewal and multi-lineage markers during long-term expansion and under neuronal and astrocyte differentiating conditions in human ESC-derived NSCs (hNSC H9 cells). In addition, with proteoglycans ubiquitous to the neural niche, we also examined heparan sulfate proteoglycans (HSPGs) and their regulatory enzymes. Our results demonstrate that hNSC H9 cells maintain self-renewal and multipotent capacity during extended culture and express HS biosynthesis enzymes and several HSPG core protein syndecans (SDCs) and glypicans (GPCs) at a high level. In addition, hNSC H9 cells exhibit high neuronal and a restricted glial differentiative potential with lineage differentiation significantly increasing expression of many HS biosynthesis enzymes. Furthermore, neuronal differentiation of the cells upregulated SDC4, GPC1, GPC2, GPC3 and GPC6 expression with increased GPC4 expression observed under astrocyte culture conditions. Finally, downregulation of selected HSPG core proteins altered hNSC H9 cell lineage potential. These findings demonstrate an involvement for HSPGs in mediating hNSC maintenance and lineage commitment and their potential use as novel markers of hNSC and neural cell lineage specification.

A 3D in vitro model reflecting the androgen deprivation state in prostate cancer bone metastasis

In castrate-resistant prostate cancer (CRPC), the prevailing organ for metastasis is bone, where the survival of cancer cells is regulated by the permissive metastatic niche offered by the bone marrow. The tumour microenvironment and cellular interactions with the matrix and bone cells enable metastasis and lead to cancer cells becoming androgen resistant. Hence, 3D models that mimic CRPC in terms of an androgen deprivation state (ADS) are needed to identify the mechanisms for CPRC growth in bone and further develop therapeutic strategies.

Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.

If dung beetles (Scarabaeidae: Scarabaeinae) arose in association with dinosaurs, did they also suffer a mass co-extinction at the K-Pg boundary?

The evolutionary success of beetles and numerous other terrestrial insects is generally attributed to co-radiation with flowering plants but most studies have focused on herbivorous or pollinating insects. Non-herbivores represent a significant proportion of beetle diversity yet potential factors that influence their diversification have been largely unexamined. In the present study, we examine the factors driving diversification within the Scarabaeidae, a speciose beetle family with a range of both herbivorous and non-herbivorous ecologies. In particular, it has been long debated whether the key event in the evolution of dung beetles (Scarabaeidae: Scarabaeinae) was an adaptation to feeding on dinosaur or mammalian dung. Here we present molecular evidence to show that the origin of dung beetles occurred in the middle of the Cretaceous, likely in association with dinosaur dung, but more surprisingly the timing is consistent with the rise of the angiosperms. We hypothesize that the switch in dinosaur diet to incorporate more nutritious and less fibrous angiosperm foliage provided a palatable dung source that ultimately created a new niche for diversification. Given the well-accepted mass extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, we examine a potential co-extinction of dung beetles due to the loss of an important evolutionary resource, i.e., dinosaur dung. The biogeography of dung beetles is also examined to explore the previously proposed "out of Africa" hypothesis. Given the inferred age of Scarabaeinae as originating in the Lower Cretaceous, the major radiation of dung feeders prior to the Cenomanian, and the early divergence of both African and Gondwanan lineages, we hypothesise that that faunal exchange between Africa and Gondwanaland occurred during the earliest evolution of the Scarabaeinae. Therefore we propose that both Gondwanan vicariance and dispersal of African lineages is responsible for present day distribution of scarabaeine dung beetles and provide examples.