623 research outputs found
Inhibition of activin/nodal signalling is necessary for pancreatic differentiation of human pluripotent stem cells
Peer reviewedPublisher PD
Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community
Background
The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention.
Methods/design
The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally.
Discussion
There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world.
The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015
TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.
The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas
Victimization of patients with severe psychiatric disorders: prevalence, risk factors, protective factors and consequences for mental health. A longitudinal study
<p>Abstract</p> <p>Background</p> <p>Victimization among people with a Severe Mental Illness is a common phenomenon. The objectives of this study proposal are: to delineate the extent and kind of victimization in a representative sample of chronic psychiatric patients; to contribute to the development and validation of a set of instruments registering victimization of psychiatric patients; to determine risk factors and protective factors; and to gain insight into the possible consequences of victimization.</p> <p>Methods/Design</p> <p>An extensive data set of 323 patients with Sever Mental Illness (assessed 4 years ago) is used. In 2010 a second measurement will be performed, enabling longitudinal research on the predictors and consequences of victimization.</p> <p>Discussion</p> <p>The consequences of (re)victimization have barely been subjected to analysis, partially due to the lack of a comprehensive, conceptual model for victimization. This research project will contribute significantly to the scientific development of the conceptual model of victimization in chronic psychiatric patients.</p
High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event
Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia
Immunogenicity Is Not Improved by Increased Antigen Dose or Booster Dosing of Seasonal Influenza Vaccine in a Randomized Trial of HIV Infected Adults
The risk of poor vaccine immunogenicity and more severe influenza disease in HIV necessitate strategies to improve vaccine efficacy.A randomized, multi-centered, controlled, vaccine trial with three parallel groups was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies were used in HIV infected adults (18 to 60 years): two standard doses over 28 days, two double doses over 28 days and a single standard dose of influenza vaccine, administered prior to the 2008 influenza season. A trivalent killed split non-adjuvanted influenza vaccine (Fluviral™) was used. Serum hemagglutinin inhibition (HAI) activity for the three influenza strains in the vaccine was measured to assess immunogenicity.297 of 298 participants received at least one injection. Baseline CD4 (median 470 cells/µL) and HIV RNA (76% of patients with viral load <50 copies/mL) were similar between groups. 89% were on HAART. The overall immunogenicity of influenza vaccine across time points and the three influenza strains assessed was poor (Range HAI ≥ 40 = 31-58%). Double dose plus double dose booster slightly increased the proportion achieving HAI titre doubling from baseline for A/Brisbane and B/Florida at weeks 4, 8 and 20 compared to standard vaccine dose. Increased immunogenicity with increased antigen dose and booster dosing was most apparent in participants with unsuppressed HIV RNA at baseline. None of 8 serious adverse events were thought to be immunization-related.Even with increased antigen dose and booster dosing, non-adjuvanted influenza vaccine immunogenicity is poor in HIV infected individuals. Alternative influenza vaccines are required in this hyporesponsive population.ClinicalTrials.gov NCT00764998
Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC
We present the first results of meson production in the K^+K^- decay channel
from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by
the PHENIX detector at RHIC. Precision resonance centroid and width values are
extracted as a function of collision centrality. No significant variation from
the PDG accepted values is observed. The transverse mass spectra are fitted
with a linear exponential function for which the derived inverse slope
parameter is seen to be constant as a function of centrality. These data are
also fitted by a hydrodynamic model with the result that the freeze-out
temperature and the expansion velocity values are consistent with the values
previously derived from fitting single hadron inclusive data. As a function of
transverse momentum the collisions scaled peripheral.to.central yield ratio RCP
for the is comparable to that of pions rather than that of protons. This result
lends support to theoretical models which distinguish between baryons and
mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be
submitted to Physical Review C as a regular article. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Incorporating ‘recruitment’ in matrix projection models : estimation, parameters, and the influence of model structure
Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Ornithology 152, Suppl.2 (2012):585-595, doi:10.1007/s10336-010-0573-1.Advances in the estimation of population parameters
using encounter data from marked individuals have
made it possible to include estimates of the probability of
recruitment in population projection models. However, the
projected growth rate of the population, and the sensitivity
of projected growth to changes in recruitment, can vary
significantly depending upon both the structural form of the
model and how recruitment is parameterized. We show that
the common practices of (1) collapsing some age classes
into a single, terminal ‘aggregated’ age-class, and (2) parameterizing
recruitment using the proportion of recruited
individuals (breeders) in a given age-class may confound
analysis of age-based (Leslie) matrix projection models in
some instances, relative to state-based projection models
where recruited and pre-recruited individuals are treated as
separate states. Failing to account for these differences can
lead to misinterpretation of the relative role of recruitment in
the dynamics of an age-structured population.We show that
such problems can be avoided, either by structural changes
to the terminal aggregated age-class in age-based models,
or by using using a state-based model instead. Since all
the metrics of general interest from a classical age-based
matrix models are readily derived from a state-based model
equivalent, this suggests there may be little reason to use the
classical age-based approach in situations where recruitment
is a parameter of interest
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