254 research outputs found
Prevalence and factors associated with parental concerns about development detected by the Parents' Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks in a birth cohort
Objectives: Early identification of developmental vulnerability is vital. This study aimed to estimate the prevalence of moderate or high developmental risk on the Parents' Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks; identify associated risk factors; and examine documentation of the PEDS at well-child checks. Design, participants: A prospective birth cohort of 2025 children with 50% of those approached agreeing to participate. Demographic data were obtained via questionnaires and linked electronic medical records. Telephone interviews were conducted with parents to collect PEDS data. Primary and secondary outcomes: Multiple logistic regression analyses identified risk factors for moderate or high developmental risk on the PEDS. A Cumulative Risk Index examined the impact of multiple risk factors on developmental risk and documentation of the PEDS at the well-child checks. Results: Of the original cohort, 792 (39%) had 6-month, 649 (32%) had 12-month and 565 (28%) had 18-month PEDS data. Parental concerns indicating moderate or high developmental risk on the PEDS were 27% (95% CI 24 to 30) at 6 months, 27% (95% CI 24 to 30) at 12 months and 33% (95% CI 29 to 37) at 18 months. Factors associated with moderate or high developmental risk were perinatal risk (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); maternal Middle Eastern or Asian nationality (OR 6 months: 1.6 (95% CI 1.1 to 2.4)), (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); and household disadvantage (OR 6 months: 1.5 (95% CI 1.0 to 2.2). As the number of risk factors increased the odds increased for high or moderate developmental risk and no documentation of the PEDS at well-child checks. Conclusions: Children with multiple risk factors are more likely to have parental concerns indicating
Stomatal Opening Involves Polar, Not Radial, Stiffening Of Guard Cells
It has long been accepted that differential radial thickening of guard cells plays an important role in the turgor-driven shape changes required for stomatal pore opening to occur [1-4]. This textbook description derives from an original interpretation of structure rather than measurement of mechanical properties. Here we show, using atomic force microscopy, that although mature guard cells display a radial gradient of stiffness, this is not present in immature guard cells, yet young stomata show a normal opening response. Finite element modeling supports the experimental observation that radial stiffening plays a very limited role in stomatal opening. In addition, our analysis reveals an unexpected stiffening of the polar regions of the stomata complexes, both in Arabidopsis and other plants, suggesting a widespread occurrence. Combined experimental data (analysis of guard cell wall epitopes and treatment of tissue with cell wall digesting enzymes, coupled with bioassay of guard cell function) plus modeling lead us to propose that polar stiffening reflects a mechanical, pectin-based pinning down of the guard cell ends, which restricts increase of stomatal complex length during opening. This is predicted to lead to an improved response sensitivity of stomatal aperture movement with respect to change of turgor pressure. Our results provide new insight into the mechanics of stomatal function, both negating an established view of the importance of radial thickening and providing evidence for a significant role for polar stiffening. Improved stomatal performance via altered cell-wall-mediated mechanics is likely to be of evolutionary and agronomic significance
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Acquired MET Expression Confers Resistance to EGFR Inhibition In a Mouse Model of Glioblastoma Multiforme
Glioblastoma Multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type EGFR and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that a key component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients
Study protocol for a real-world evaluation of an integrated child and family health hub for migrant and refugee women
Introduction Continuity of child and family healthcare is vital for optimal child health and development for developmentally vulnerable children. Migrant and refugee communities are often at-risk of poor health outcomes, facing barriers to health service attendance including cultural, language, limited health literacy, discrimination and unmet psychosocial needs. 'Integrated health-social care hubs' are physical hubs where health and social services are co-located, with shared referral pathways and care navigation. Aim Our study will evaluate the impact, implementation and cost-benefit of the First 2000 Days Care Connect (FDCC) integrated hub model for pregnant migrant and refugee women and their infants. Materials and methods This study has three components. Component 1 is a non-randomised controlled trial to compare the FDCC model of care with usual care. This trial will allocate eligible women to intervention and control groups based on their proximity to the Hub sites. Outcome measures include: the proportion of children attending child and family health (CFH) nurse services and completing their CFH checks to 12 months of age; improved surveillance of growth and development in children up to 12 months, post partum; improved breastfeeding rates; reduced emergency department presentations; and improved maternal well-being. These will be measured using linked medical record data and surveys. Component 2 will involve a mixed-method implementation evaluation to clarify how and why FDCC was implemented within the sites to inform future roll-out. Component 3 is a within-trial economic evaluation from a healthcare perspective to assess the cost-effectiveness of the Hubs relative to usual care and the implementation costs if Hubs were scaled and replicated. Ethics and dissemination Ethical approval was granted by the South Eastern Sydney Local Health District Human Research Ethics Committee in July 2021 (Project ID: 020/ETH03295). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences. Trial registration number ACTRN12621001088831
Selection and inheritance of sexually dimorphic juvenile plumage coloration
Sexually dimorphic plumage coloration is widespread in birds and is generally thought to be a result of sexual selection for more ornamented males. Although many studies find an association between coloration and fitness related traits, few of these simultaneously examine selection and inheritance. Theory predicts that sex-linked genetic variation can facilitate the evolution of dimorphism, and some empirical work supports this, but we still know very little about the extent of sex linkage of sexually dimorphic traits. We used a longitudinal study on juvenile Florida scrub-jays (Aphelocoma coerulescens) to estimate strength of selection and autosomal and Z-linked heritability of mean brightness, UV chroma, and hue. Although plumage coloration signals dominance in juveniles, there was no indication that plumage coloration was related to whether or not an individual bred or its lifetime reproductive success. While mean brightness and UV chroma are moderately heritable, hue is not. There was no evidence for sex-linked inheritance of any trait with most of the variation explained by maternal effects. The genetic correlation between the sexes was high and not significantly different from unity. These results indicate that evolution of sexual dimorphism in this species is constrained by low sex-linked heritability and high intersexual genetic correlation.Peer reviewe
SeaWiFS Postlaunch Technical Report Series
This report documents the scientific activities on board the Royal Research Ship (RRS) James Clark Ross (JCR) during the fifth Atlantic Meridional Transect (AMT-5), 14 September to 17 October 1997. There are three objectives of the AMT Program. The first is to derive an improved understanding of the links between biogeochemical processes, biogenic gas exchange, air-sea interactions, and the effects on, and responses of, oceanic ecosystems to climate change. The second is to investigate the functional roles of biological particles and processes that influence ocean color in ecosystem dynamics. The Program relates directly to algorithm development and the validation of remotely-sensed observations of ocean color. Because the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) instrument achieved operational status during the cruise (on 18 September), AMT-5 was designated the SeaWiFS Atlantic Characterization Experiment (SeaACE) and was the only major research cruise involved in the validation of SeaWiFS data during the first 100 days of operations. The third objective involved the near-real time reporting of in situ light and pigment observations to the SeaWiFS Project, so the performance of the satellite sensor could be determined
The rate of telomere loss is related to maximum lifespan in birds
Telomeres are highly conserved regions of DNA that protect the ends of linear chromosomes. The loss of telomeres can signal an irreversible change to a cell's state, including cellular senescence. Senescent cells no longer divide and can damage nearby healthy cells, thus potentially placing them at the crossroads of cancer and ageing. While the epidemiology, cellular and molecular biology of telomeres are well studied, a newer field exploring telomere biology in the context of ecology and evolution is just emerging. With work to date focusing on how telomere shortening relates to individual mortality, less is known about how telomeres relate to ageing rates across species. Here, we investigated telomere length in cross-sectional samples from 19 bird species to determine how rates of telomere loss relate to interspecific variation in maximum lifespan. We found that bird species with longer lifespans lose fewer telomeric repeats each year compared with species with shorter lifespans. In addition, phylogenetic analysis revealed that the rate of telomere loss is evolutionarily conserved within bird families. This suggests that the physiological causes of telomere shortening, or the ability to maintain telomeres, are features that may be responsible for, or co-evolved with, different lifespans observed across species.This article is part of the theme issue 'Understanding diversity in telomere dynamics'
Miocene waterfowl and other birds from central Otago, New Zealand
Copyright © The Natural History Museum 2007Abundant fossil bird bones from the lower Bannockburn Formation, Manuherikia Group, an Early-Middle Miocene lacustrine deposit, 16â19 Ma, from Otago in New Zealand, reveal the âSt Bathans Faunaâ (new name), a first Tertiary avifauna of land and freshwater birds from New Zealand. At least 23 species of birds are represented by bones, and probable moa, Aves: Dinornithiformes, by eggshell. Anatids dominate the fauna with four genera and five species described as new: a sixth and largest anatid species is represented by just one bone. This is the most diverse Early-Middle Miocene duck fauna known worldwide. Among ducks, two species of dendrochenines are most numerous in the fauna, but a tadornine is common as well. A diving petrel (Pelecanoididae: Pelecanoides) is described, so extending the geological range of this genus worldwide from the Pliocene to the Middle Miocene, at least. The remaining 16 taxa are left undescribed but include: a large species of gull (Laridae); two small waders (Charadriiformes, genus indet.), the size of Charadrius bicinctus and Calidris ruficollis, respectively; a gruiform represented by one specimen similar to Aptornis; abundant rail (Rallidae) bones, including a common flightless rail and a rarer slightly larger taxon, about the size of Gallirallus philippensis; an ?eagle (Accipitridae); a pigeon (Columbidae); three parrots (Psittacidae); an owlet nightjar (Aegothelidae: Aegotheles sp.); a swiftlet (Apodidae: Collocalia sp.); and three passerine taxa, of which the largest is a member of the Cracticidae. The absence of some waterbirds, such as anserines (including swans), grebes (Podicipedidae) and shags (Phalacrocoracidae), among the abundant bones, indicates their probable absence from New Zealand in the Early-Middle Miocene.T. H. Worthy, A. J. D. Tennyson, C. Jones, J. A. McNamara and B. J. Dougla
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