Maternal obesity, gestational weight gain, and child cognition, behavior, and academic achievement

Attention-deficit hyperactivity disorder (ADHD) is the most prevalent developmental disability in the United States and can compromise a child’s behavioral and intellectual development. We used a longitudinal birth cohort from Pittsburgh, PA to study maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) in relation to 1) offspring intelligence and executive function at age ten 2) offspring behavior and ADHD symptoms at age ten 3) offspring academic achievement at ages six, ten, and fourteen. Mother-child pairs (n=763) from the Maternal Health Practices and Child Development pregnancy cohort were followed from <21 weeks gestation to 14 years postpartum. Self-reported total GWG was classified using gestational-age standardized z-score charts and BMI was categorized in accordance with the World Health Organization (WHO) criteria. Validated assessment tools were used to measure child intelligence, executive function, and behaviors consistent with attention-deficit hyperactivity disorder (ADHD) as well as academic achievement. Compared with children of normal weight mothers, offspring of obese mothers had 3.2 lower IQ points (95% CI: -5.6, -0.8), were 12.7 seconds slower on the executive function scale (95% CI: 2.8, 22.7), and had increased problem behaviors consistent with ADHD including withdrawn or somatic complaints (adj β: 4.9 points, 95% CI: 1.7, 8.1), delinquent or aggressive behaviors (adj β: 4.2 points, 95% CI: 1.1, 7.3), and attention problems (adj β: 3.5 points, 95% CI: 1.2, 5.8) after adjusting for confounders. Academic achievement was also lower among children of obese mothers, compared with children of normal weight mothers. In generalized estimating equation models, high GWG was significantly associated with a 4 point decrease in reading (adjβ: -3.75, 95% CI: -7.1, -0.4) and spelling scores (adjβ: -3.90, 95% CI: -7.8, -0.2) at ages 6, 10, and 14. There was a non-significant trend towards lower offspring domain-specific cognition with high maternal GWG. This dissertation is important to public health because pre-pregnancy BMI and GWG are potentially modifiable factors and a reduction in obesity and excessive GWG could alleviate, although not eliminate, the burden of ADHD and related impairments in the population

Comparing and Combining Lexicase Selection and Novelty Search

Lexicase selection and novelty search, two parent selection methods used in evolutionary computation, emphasize exploring widely in the search space more than traditional methods such as tournament selection. However, lexicase selection is not explicitly driven to select for novelty in the population, and novelty search suffers from lack of direction toward a goal, especially in unconstrained, highly-dimensional spaces. We combine the strengths of lexicase selection and novelty search by creating a novelty score for each test case, and adding those novelty scores to the normal error values used in lexicase selection. We use this new novelty-lexicase selection to solve automatic program synthesis problems, and find it significantly outperforms both novelty search and lexicase selection. Additionally, we find that novelty search has very little success in the problem domain of program synthesis. We explore the effects of each of these methods on population diversity and long-term problem solving performance, and give evidence to support the hypothesis that novelty-lexicase selection resists converging to local optima better than lexicase selection

Trust-building vs. “just trust me”: reflexivity and resonance in ethnography

Amidst a perceived credibility crisis, recent scholarship has challenged basic norms of how ethnographies are conducted. This article identifies, underlying these critiques, a “trust me” fallacy that misunderstands ethnography as requiring blind trust in the researcher, leading to proposed reforms that promote extractive research practices by treating truths as raw commodities to be traded in for credibility. We argue such practices are unlikely to resolve critics' concerns, and at the same time, they challenge the ethnographic capacity for resonance. Building on recent work in cultural sociology, we elaborate and refine a “textured model of resonance” to capture one of ethnography's unique contributions: excavating ambivalence, plurality and complexity. We conclude by noting how time-honored practices of reflexivity, honed through productive dialogue among practitioners, address issues of trust and reliability without threatening what ethnography does well

Developing Local Entrepreneurial Ecosystems through Integrated Learning Initiatives:The Lancaster Case

This paper considers a concept gaining popularity: entrepreneurial ecosystems. It finds a significant lacuna in the concept as it stands as it does not sufficiently consider learning within regional ecosystems. Considering the established centrality of learning for entrepreneurial activity and regional development, it is surprising that the entrepreneurial ecosystems literature does not yet incorporate how learning occurs in time and space within regional ecosystems. This paper presents research conducted in the North West of England over (twenty) years examining programmes to support entrepreneurial and regional development. It argues that learning, and the pro-active support thereof, is crucial within an entrepreneurial ecosystem and should be fully considered within theoretical frameworks and policy blueprints designed to support and encourage entrepreneurship within regions. As a tangible suggestion of how to theoretically incorporate learning into entrepreneurship ecosystem development efforts, we present an Integrated Learning Model developed by entrepreneurship scholars through collaborations with practitioners

Loss‐of‐function mutations in the <i>ALPL </i>gene presenting with adult onset osteoporosis and low serum concentrations of total alkaline phosphatase

Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic‐based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10‐year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss‐of‐function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

A step into the unknown:universities and the governance of regional economic development

As the social and economic landscape changes, universities are coming under growing pressure to contribute to the economic development of their localities. This paper explores the increasing trends towards universities as key actors in the governance of regional economic development through activities to support economic and entrepreneurship development in their regions. A case study is presented of an institution in the UK which is increasingly situating itself in the economic governance sphere. Drawing on the experiences of those working at the coalface of economic governance activities, the opportunities and potential challenges faced by a university when engaging in such activities are explored. The ultimate goal of this paper is to shed light on universities’ activities in the realm of regional economic governance, an area currently under-explored in extant literature

Linked mutations at adjacent nucleotides have shaped human population differentiation and protein evolution

Despite the fundamental importance of single nucleotide polymorphisms (SNPs) to human evolution, there are still large gaps in our understanding of the forces that shape their distribution across the genome. SNPs have been shown to not be distributed evenly, with directly adjacent SNPs found unusually frequently. Why this is the case is unclear. We illustrate how neighboring SNPs that cannot be explained by a single mutation event (that we term here sequential dinucleotide mutations [SDMs]) are driven by distinct processes to SNPs and multinucleotide polymorphisms (MNPs). By studying variation across populations, including a novel cohort of 1,358 Scottish genomes, we show that, SDMs are over twice as common as MNPs and like SNPs display distinct mutational spectra across populations. These biases are not only different to those observed among SNPs and MNPs but are also more divergent between human population groups. We show that the changes that make up SDMs are not independent and identify a distinct mutational profile, CA → CG → TG, that is observed an order of magnitude more often than expected from background SNP rates and the numbers of other SDMs involving the gain and deamination of CpG sites. Intriguingly particular pathways through the amino acid code appear to have been favored relative to that expected from intergenic SDM rates and the occurrences of coding SNPs, and in particular those that lead to the creation of single codon amino acids. We finally present evidence that epistatic selection has potentially disfavored sequential nonsynonymous changes in the human genome