Number Sense and Mathematics: Which, When and How?

Individual differences in number sense correlate with mathematical ability and performance, although the presence and strength of this relationship differs across studies. Inconsistencies in the literature may stem from heterogeneity of number sense and mathematical ability constructs. Sample characteristics may also play a role as changes in the relationship between number sense and mathematics may differ across development and cultural contexts. In this study, 4,984 16-year-old students were assessed on estimation ability, one aspect of number sense. Estimation was measured using two different tasks: number line and dot-comparison. Using cognitive and achievement data previously collected from these students at ages 7, 9, 10, 12, and 14 years of age, the study explored for which of the measures and when in development these links are observed; how strong these links are and how much these links are moderated by other cognitive abilities. The two number sensemeasures correlated modestly with each other (r = .22), but moderately with mathematics at age 16. Both measures were also associated with earlier mathematics; but this association was uneven across development and was moderated by other cognitive abilities

Twin classroom dilemma: To study together or separately?

There is little research to date on the academic implications of teaching twins in the same or different classroom.Consequently, it is not clear whether twin classroom separation is associated with positive or negative educational outcomes. As a result, parents and teachers have insufficient evidence to make a well-informed decision when twins start school. This study addresses two research questions: Are there average positive or negative effects of classroom separation? Are twins taught in different classes more different from each other than twins taught in the same class? Twin pairs from two large representative samples from Quebec (Canada) and the UKwere evaluated across a large age range (7 to 16 years) onacademic achievement, severalcognitive abilities and motivational measures. Our results show almost no sizeable positive or negative average effect of classroom separation on twins’ achievement, cognitive ability and motivation. Twin pairs at age 12 (Quebec, Canada) and at age 16 (UK) were slightly more similar on achievement if placed in the same classroom, with slightly greater similarity among MZ twins than DZ twins. However, the few effects found were weak,and it remainsunclear whether they result from classroom separation orother factors. These results suggest that in terms of educational outcomes, policy makers should not impose rigid guidelines to separate twin pairs during their education. The choice of whether to educate twin pairs together or separately should be up to parents, twins and teachers, in response to twins’ individual needs

Development and validation of a mathematics-number sense web-based test battery.

This study aimed to create and validate a web-based battery of tests, age appropriate for 16 year-olds, and designed to assess mathematical skills, general cognitive abilities and number sense. The first stage of the study involved the selection of 11 measures and their administration to a sample of 100 16 year-old students, either in pen and paper format, or on computers. Guided by reliability analyses conducted on the first phase's data, 6 of these tests were selected and implemented online. The new battery revealed to be a reliable tool of assessment showing good internal validity and reliability for all the measures

From classroom environment to mathematics achievement: The mediating role of self-perceived ability and subject interest

Drawing on Bandura's triadic reciprocal causation model, perceived classroom environment and three intrapersonal factors (mathematics self-efficacy, maths interest and academic self-concept) were considered as predictors of test performance in two correlated mathematics assessments: a public examination (GCSE) and an on-line test, both taken by UK pupils at age 16 (n = 6689). Intrapersonal factors were significantly associated with both test scores, even when the alternative score was taken into account. Classroom environment did not correlate with mathematics achievement once intrapersonal factors and alternative test performance were included in the model, but was associated with subject interest and academic self-concept. Perceptions of classroom environment may exercise an indirect influence on achievement by boosting interest and self-concept. In turn, these intrapersonal factors have direct relationships with achievement and were found to mediate the relationship between perceived classroom environment and maths performance. Findings and their implications for mathematics education are discussed

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study

Sex Differences in Non-Verbal and Verbal Abilities in Childhood and Adolescence

Twin research has shown that females with male co-twins perform better than females with female co-twins on mental rotation. This beneficial effect of having a male sibling on spatial ability could be due to in-uterine transmission of testosterone from males to females (the Twin Testosterone Transfer hypothesis, TTT). The present study explored sex differences and the TTT in non-verbal and verbal abilities in a large sample of twins assessed longitudinally at 2, 3, 4, 7, 9, 10, 12, 14 and 16 years of age. Females scored significantly higher than males on both verbal and non-verbal abilities at ages 2, 3 and 4. Males scored significantly higher than females on verbal ability at ages 10 and 12. The effect sizes of all differences were very small. No sex differences in non-verbal or verbal abilities were found at 7, 9, 14 and 16 years of age. No support for the TTT was found at any age. The findings indicate that the twin testosterone transfer effect occurs only for specific cognitive abilities, such as mental rotation

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 × 10 -10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10 -7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD

Promising Therapies for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most frequent progressive neurodegenerative disease. Cholinergic dysfunction is one of the major pathological alteration, although depletion of cholinergic neurons is caused by the well-established toxicity of the beta-amyloid plaques and neurofibrillary tangles. Cholinergic dysfunctions are consequences of the decrease in acetylcholine synthesis and release, and altered function of muscarinic and nicotinic cholinergic receptors. In addition, a direct correlation between cholinergic alteration, amyloidbeta production and tau phosphorylation, two main AD-pathology hallmarks, has been identified. METHODS: In the present review we focused our discussion on the identification of new allosteric or bitopic ligands able to modulate the cholinergic receptor activity. Moreover drug delivery methodology (nanoparticeles, liposomes, etc.) that might contribute to drive the drug in the brain, reducing their toxicity and potential side effects have been also discussed. RESULTS: Many drugs are currently in use for AD (e.g. donepezil, rivastigmine etc.) and several of those in development such as muscarininc and nicotinic agonists, target specifically the cholinergic system; the main mechanism aims to rescue the cholinergic dysfunction, to reduce neurotoxic protein accumulation and improve the cholinergic impairments responsible of the cognitive deficits. Promising approaches aim to either improve drug delivery into the brain or develope new compounds targeting known or new molecular pathways. Nanoparticles and liposomes are also described as new nanotechnology tools that overcome traditional routes of administration, with a particular focus on their employment for compounddelivery that targets the cholinergic system. Ultimately, a new fields of research is emerging as the use of induced pluripotent stem cells, a technology that allows to obtain cells directly from the patients that can be propagated indefinetely and differentiated into the susceptible neuronal subtypes. This may significantly contribute to improve the understanding of AD pathological processes and enhance current AD pharmacology beyond the cholinergic dysfunction. CONCLUSION: From the topics discussed in the present review, emerges that the combination between pharmacological studies and nanotechnological approaches for drug delivery and the identification of new specific models may largely enhance and improve the therapeutic strategies for different neurological disease including AD