DEVELOPMENTAL ORIGINS OF METABOLIC DISEASES

Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the “double burden of malnutrition,” where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases

A Brachistochrone Approach to Reconstruct the Inflaton Potential

We propose a new way to implement an inflationary prior to a cosmological dataset that incorporates the inflationary observables at arbitrary order. This approach employs an exponential form for the Hubble parameter $H(\phi)$ without taking the slow-roll approximation. At lowest non-trivial order, this $H(\phi)$ has the unique property that it is the solution to the brachistochrone problem for inflation.Comment: 13 pages, 2 figures, version matches published versio

Geographic Proximity Not a Prerequisite for Invasion: Hawaii Not the Source of California Invasion by Light Brown Apple Moth (Epiphyas postvittana)

BACKGROUND: The light brown apple moth (LBAM), Epiphyas postvittana (Walker), is native to Australia but invaded England, New Zealand, and Hawaii more than 100 years ago. In temperate climates, LBAM can be a major agricultural pest. In 2006 LBAM was discovered in California, instigating eradication efforts and quarantine against Hawaiian agriculture, the assumption being that Hawaii was the source of the California infestation. Genetic relationships among populations in Hawaii, California, and New Zealand are crucial to understanding LBAM invasion dynamics across the Pacific. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced mitochondrial DNA (mtDNA) from 1293 LBAM individuals from California (695), Hawaii (448), New Zealand (147), and Australia (3) to examine haplotype diversity and structure among introduced populations, and evaluate the null hypothesis that invasive populations are from a single panmictic source. However, invasive populations in California and New Zealand harbor deep genetic diversity, whereas Hawaii shows low level, shallow diversity. CONCLUSIONS/SIGNIFICANCE: LBAM recently has established itself in California, but was in Hawaii and New Zealand for hundreds of generations, yet California and New Zealand show similar levels of genetic diversity relative to Hawaii. Thus, there is no clear relationship between duration of invasion and genetic structure. Demographic statistics suggest rapid expansion occurring in California and past expansions in New Zealand; multiple introductions of diverse, genetically fragmented lineages could contribute to these patterns. Hawaii and California share no haplotypes, therefore, Hawaii is not the source of the California introduction. Paradoxically, Hawaii and California share multiple haplotypes with New Zealand. New Zealand may be the source for the California and Hawaii infestations, but the introductions were independent, and Hawaii was invaded only once. This has significant implications for quarantine, and suggests that probability of invasion is not directly related to geographic distance. Surprisingly, Hawaiian LBAM populations have much lower genetic diversity than California, despite being older

Constrained Hyperbolic Divergence Cleaning for Smoothed Particle Magnetohydrodynamics

We present a constrained formulation of Dedner et al's hyperbolic/parabolic divergence cleaning scheme for enforcing the \nabla\dot B = 0 constraint in Smoothed Particle Magnetohydrodynamics (SPMHD) simulations. The constraint we impose is that energy removed must either be conserved or dissipated, such that the scheme is guaranteed to decrease the overall magnetic energy. This is shown to require use of conjugate numerical operators for evaluating \nabla\dot B and \nabla{\psi} in the SPMHD cleaning equations. The resulting scheme is shown to be stable at density jumps and free boundaries, in contrast to an earlier implementation by Price & Monaghan (2005). Optimal values of the damping parameter are found to be {\sigma} = 0.2-0.3 in 2D and {\sigma} = 0.8-1.2 in 3D. With these parameters, our constrained Hamiltonian formulation is found to provide an effective means of enforcing the divergence constraint in SPMHD, typically maintaining average values of h |\nabla\dot B| / |B| to 0.1-1%, up to an order of magnitude better than artificial resistivity without the associated dissipation in the physical field. Furthermore, when applied to realistic, 3D simulations we find an improvement of up to two orders of magnitude in momentum conservation with a corresponding improvement in numerical stability at essentially zero additional computational expense.Comment: 28 pages, 25 figures, accepted to J. Comput. Phys. Movies at http://www.youtube.com/playlist?list=PL215D649FD0BDA466 v2: fixed inverted figs 1,4,6, and several color bar

Multiple health-related behaviours among Fly-In Fly-Out workers in the mining industry in Australia : A cross-sectional survey during the COVID-19 pandemic

Funding: The study received funding from Mineral Resources Limited (Australia). Mineral ResourcesLimited provided AUS$ 200 shopping voucher to the winner of a raffle draw as reimbursement for study participation. Mineral Resources Limited (Australia) provided support for this study in the form of salaries to authors MS and CH. The specific roles of these authors are articulated in the ‘author contributions’ section. Employees of Mineral Resources Limited played role in the datacollection, interpretation of study findings, preparation and decision to submit this manuscript for publication but not in the design of the study and data analysis. The preparation of this manuscript was supported by the Aberdeen-Curtin Alliance International Postgraduate Research Scholarship scheme awarded to BY-AA.Peer reviewedPublisher PD

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Taselisib (GDC-0032), a Potent -Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations

Activating PIK3CA genomic alterations are frequent in head and neck squamous cell carcinoma (HNSCC), and there is an association between phosphoinositide 3-kinase (PI3K) signaling and radioresistance. Hence, we investigated the therapeutic efficacy of inhibiting PI3K with GDC-0032, a PI3K inhibitor with potent activity against p110α, in combination with radiation in HNSCC

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

Mental Well-Being during COVID-19 : A Cross-Sectional Study of Fly-In Fly-Out Workers in the Mining Industry in Australia

Funding: This study was funded by the Mineral Resources Limited (Australia). Mineral Resources Limited provided AUD 200 shopping voucher to the winner of a raffle draw as reimbursement for study participation. Mineral Resources Limited played role in the data collection, interpretation of study findings, preparation and decision to submit this manuscript for publication but not in the design of the study and data analysis. The study was supported by Aberdeen-Curtin Alliance Curtin International Postgraduate Research Scholarship (CIPRS) in the writing of the manuscript. B.Y.-A.A. is a recipient of Aberdeen-Curtin Alliance PhD Curtin International Postgraduate Research Scholarship (CIPRS) and Research Stipend Scholarship. Acknowledgments: We express our profound gratitude to the Mineral Resources Limited, Australia for their support in advertising the study and allowing for us undertake this study among their workers. We also extend our appreciation to all the FIFO workers who took time to participate in this study.Peer reviewedPublisher PD

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies