Towards an understanding of fidelity within the context of school-based health education

Schools and schooling have long provided a tempting site for the delivery of public health strategies that address and promote young people's current and future health. However, an emerging concern regarding the mobilisation of public health interventions within school settings has been the failure of school teachers to deliver such programs with fidelity. For educators, these notions of fidelity stand in stark contrast to the tenets of student-centred teaching. In seeking to explore these tensions further, this paper draws upon a collaborative health education project conducted with schools and teachers from Queensland, Australia. Findings from this project reveal the complexity associated with curriculum implementation in school settings, where diverse resources including timetable allocations and teacher expertise mitigate the achievement of program fidelity. In our efforts to explain the findings emerging from this project, we have drawn on the conceptual reference points of Basil Bernstein's theory of the pedagogic device to reveal the predictable misalignment of the health and education sectors' expected outcomes of school-based health initiatives. In conclusion, we argue that our exploration of issues pertaining to fidelity demonstrates the need for health and education sectors alike to conduct their work according to a clear articulation of the realistic, educative role that schools can play in promoting healthy living

Evidence for two stages of mineralization in West Africa's largest gold deposit: Obuasi, Ghana

The supergiant Obuasi gold deposit is the largest deposit in the Paleoproterozoic Birimian terranes of West Africa with 62 Moz of gold (past production + resources). The deposit is hosted in the Paleoproterozoic Kumasi Group sedimentary rocks composed of carbonaceous phyllites, slates, psammites, and volcaniclastic rocks intruded by different generations of felsic dikes and granites. A three-stage deformation history is defined for the district. The D1Ob stage is weakly recorded in the sedimentary rocks as a layer-parallel fabric and indicates that bedding parallel shearing occurred during the early stage of deformation at Obuasi. The D2Ob is the main deformation stage affecting the Obuasi district and corresponds to a NW-SE shortening. Tight to isoclinal folding, as well as intense subhorizontal stretching, occurred during D2Ob, parallel with the plane of a pervasive NE-striking subvertical foliation (S2Ob). Finally, a N-S shortening event (D3Ob) refolded previously formed structures and formed a distinct ENE-striking, variably dipping S3Ob cleavage that is domainal in nature throughout the deposit. Two economic styles of mineralization occur at Obuasi and contribute equally to the gold budget. These are (1) gold-bearing sulfides, dominantly arsenopyrite, mainly disseminated in metasedimentary rocks and (2) native gold hosted in quartz veins that are as much as 25 m wide. Microstructural evidence, such as strain shadows surrounding gold-bearing arsenopyrite parallel with S2Ob, but folded by S3Ob, indicates that the sulfides were formed during D2Ob. Concentrations of as much as 700 ppm Au are present in the epitaxial growth zones of the arsenopyrite grains. Although the large mineralized quartz veins are boudinaged and refolded (indicating their formation during D2Ob), field and microanalytical observations demonstrate that the gold in the veins is hosted in microcracks controlled by D3Ob, where the S3Ob cleavage crosscuts the quartz veins in the main ore zones. Thus, these observations constitute the first evidence for multiple stages of gold deposition at the Obuasi deposit. Futhermore, three-dimensional modeling of stratigraphy, structure, and gold orebodies highlights three major controls on oreshoot location, which are (1) contacts between volcaniclastic units and pre-D1 felsic dikes, (2) fault intersections, and (3) F3Ob fold hinges. The maximum age for the older disseminated gold event is given by the age of the granites at 2105 ± 2 Ma, which is within error of hydrothermal rutile in the granites of 2098 ± 7 Ma; the absolute age of the younger gold event is not known

The biological and clinical significance of stromal-epithelial interactions in breast cancer

There is evidence that an aberrant tumour microenvironment (TME) facilitates cancer development, progression, and responses to treatment. While many of the mechanisms underlying the phenotype and cancer-promoting behaviour of the TME are unknown, epigenetic mechanisms in cancer cells and the TME are thought to play important roles. As a result, cancer profiling strategies for drug and biomarker development require a thorough understanding of both the epithelial tissue compartment and the TME. This review discusses recent advances in our understanding of how cancer epithelial cells interact with their microenvironment and how this knowledge can be exploited clinically.The original research presented in this review was supported under NHMRC Projects funding scheme (project number APP1048065

Genomic Organization, Splice Variants and Expression of CGMl, a CD66-related Member of the Carcinoembryonic Antigen Gene Family

The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunogiobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGMI. a transmembrane member of the CEA family without immunoglobulin constant.like domains. CGM1a and CGM1c contain cytopiasmic domains of 71 and 31 amino acids, respectively, The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp)..

Chromatinized Protein Kinase C-θ: Can It Escape the Clutches of NF-κB?

We recently provided the first description of a nuclear mechanism used by Protein Kinase C-theta (PKC-θ) to mediate T cell gene expression. In this mode, PKC-θ tethers to chromatin to form an active nuclear complex by interacting with proteins including RNA polymerase II, the histone kinase MSK-1, the demethylase LSD1, and the adaptor molecule 14-3-3ζ at regulatory regions of inducible immune response genes. Moreover, our genome-wide analysis identified many novel PKC-θ target genes and microRNAs implicated in T cell development, differentiation, apoptosis, and proliferation. We have expanded our ChIP-on-chip analysis and have now identified a transcription factor motif containing NF-κB binding sites that may facilitate recruitment of PKC-θ to chromatin at coding genes. Furthermore, NF-κB association with chromatin appears to be a prerequisite for the assembly of the PKC-θ active complex. In contrast, a distinct NF-κB-containing module appears to operate at PKC-θ targeted microRNA genes, and here NF-κB negatively regulates microRNA gene transcription. Our efforts are also focusing on distinguishing between the nuclear and cytoplasmic functions of PKCs to ascertain how these kinases may synergize their roles as both cytoplasmic signaling proteins and their functions on the chromatin template, together enabling rapid induction of eukaryotic genes. We have identified an alternative sequence within PKC-θ that appears to be important for nuclear translocation of this kinase. Understanding the molecular mechanisms used by signal transduction kinases to elicit specific and distinct transcriptional programs in T cells will enable scientists to refine current therapeutic strategies for autoimmune diseases and cancer

Development and Microstructural Improvement of Spin Cast High-Speed Steel Rolls

A detailed microstructural analysis was conducted on a series of radial shell samples extracted from commercially produced centrifugally spin casted high-speed steel (HSS) work rolls for finishing hot strip mills (HSM). The systematic microstructural analysis was coupled with a numerical and experimental investigation to improve the life of HSS rolls. An integrated computational-experimental approach was developed to optimize the response of the HSS roll material that permitted the enhancement of the microstructure and properties of the HSS roll shell layer. Local continuous microstructural transformations through the thickness of the shell: carbide formation, precipitation, dissolution sequence and phase changes, were studied in great details. The analyses were conducted with the aid of advanced metallographic and experimental methods, finite-element (FE) analysis, and using commercial software systems to conduct thermodynamic-kinetics predictions. In order to analyze a response of the HSS roll to the hardening heat treatment (HT) and to control stress-strain evolution, a 3-D FE model was developed of the composite structure of the roll. The multilayered model considers nonlinear material properties of each individual layer as a function of temperature, based on measured chemical composition gradients through the HSS shell. Transient coupled thermal-stress analysis was performed, using actual measured surface temperatures as boundary conditions (BC) for the FE model. The allowable thermal stress-strain levels were established and compared with a) thermodynamically predicted high temperature mechanical properties and b) room temperature test results of the shear strengths for the shell, bonding and core. In addition, sub-structuring and image-based processing techniques were implemented to aid in the development of a meso-scale FE model to simulate the local response of a given microstructural constituents and matrix under particular thermal conditions. The fundamental interpretation of multilayered structure and multi-scale approach help to understand the kinetics phenomena associated with continuous local microstructural transformations due to nonlinear heat transfer. The results from the microstructural observations were in good agreement with the numerical predictions. The major impact of this work clearly indicated that a refined as-cast structure prior to the heat treatment promoted an increased precipitation of carbides during final hardening, which greatly improved strength and performance. A non-conventional HT was defined and implemented in order to provide an additional degree of microstructural pre-conditioning, which homogenized the matrix throughout the HSS shell. The new HT defined the austenitization temperatures and times to modify the morphology of brittle interdendritic eutectic carbide networks and, hence, facilitating the kinetics of dissolution of these carbides. This behavior caused an increase in the solute content of the matrix. As a result, the matrix hardness and strength were increased during subsequent hardening HT in comparison to the conventional HT routes used for as-cast HSS rolls. Reports about rolls with the new material that have been placed in service indicate that the rolls last 50-70% longer

Geological archive of the onset of plate tectonics

© 2018 The Author(s) Published by the Royal Society. All rights reserved. Plate tectonics, involving a globally linked system of lateral motion of rigid surface plates, is a characteristic feature of our planet, but estimates of how long it has been the modus operandi of lithospheric formation and interactions range from the Hadean to the Neoproterozoic. In this paper, we review sedimentary, igneous and metamorphic proxies along with palaeomagnetic data to infer both the development of rigid lithospheric plates and their independent relative motion, and conclude that significant changes in Earth behaviour occurred in the mid- to late Archaean, between 3.2 Ga and 2.5 Ga. These data include: sedimentary rock associations inferred to have accumulated in passive continental margin settings, marking the onset of seafloor spreading; the oldest foreland basin deposits associated with lithospheric convergence; a change from thin, new continental crust of mafic composition to thicker crust of intermediate composition, increased crustal reworking and the emplacement of potassic and peraluminous granites, indicating stabilization of the lithosphere; replacement of dome and keel structures in granite-greenstone terranes, which relate to vertical tectonics, by linear thrust imbricated belts; the commencement of temporally paired systems of intermediate and high dT/dP gradients, with the former interpreted to represent subduction to collisional settings and the latter representing possible hinterland back-arc settings or ocean plateau environments. Palaeomagnetic data from the Kaapvaal and Pilbara cratons for the interval 2780-2710Ma and from the Superior, Kaapvaal and Kola-Karelia cratons for 2700-2440Ma suggest significant relative movements. We consider these changes in the behaviour and character of the lithosphere to be consistent with a gestational transition from a non-plate tectonic mode, arguably with localized subduction, to the onset of sustained plate tectonics

Management of infantile hemangiomas during the COVID pandemic

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The COVID‐19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long‐term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA‐approved monitoring guidelines, clinical practice guidelines, and relevant, up‐to‐date publications regarding initiation and monitoring of beta‐blocker therapy were used to inform the recommendations. Clinical decision‐making guidelines about when telehealth is an appropriate alternative to in‐office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided

LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer

Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.T. Boulding, R.D. McCuaig, A. Tan, K. Hardy, F. Wu, J. Dunn, M. Kalimutho, C.R. Sutton, J.K. Forwood, A.G. Bert, G.J. Goodall, L. Malik, D. Yip, J.E. Dahlstrom, A. Zafar, K.K. Khanna, S. Ra