Introducing research initiatives into healthcare: What do doctors think?

Background: Current national and international policies emphasize the need to develop research initiatives within our health care system. Institutional biobanking represents a modern, large-scale research initiative that is reliant upon the support of several aspects of the health care organization. This research project aims to explore doctors' views on the concept of institutional biobanking and to gain insight into the factors which impact the development of research initiatives within healthcare systems. Methods: Qualitative research study using semi-structured interviews. The research was conducted across two public teaching hospitals in Sydney, Australia where institutional biobanking was being introduced. Twenty-five participants were interviewed, of whom 21 were medical practitioners at the specialist trainee level or above in a specialty directly related to biobanking; four were key stakeholders responsible for the design and implementation of the biobanking initiative. Results: All participants strongly supported the concept of institutional biobanking. Participants highlighted the discordance between the doctors who work to establish the biobank (the contributors) and the researchers who use it (the consumers). Participants identified several barriers that limit the success of research initiatives in the hospital setting including: the 'resistance to change' culture; the difficulties in engaging health professionals in research initiatives; and the lack of incentives offered to doctors for their contribution. Doctors positively valued the opportunity to advise the implementation team, and felt that the initiative could benefit from their knowledge and expertise. Conclusion: Successful integration of research initiatives into hospitals requires early collaboration between the implementing team and the health care professionals to produce a plan that is sensitive to the needs of the health professionals and tailored to the hospital setting. Research initiatives must consider incentives that encourage doctors to adopt operational responsibility for hospital research initiatives

Student Awareness of Models in First-Year Engineering Courses

Contribution: This study assesses more than 800 students\u27 awareness of engineering model types before and after taking two first-year engineering courses across two semesters and evaluates the effect of each course. Background: All engineers must be able to apply and create models to be effective problem solvers, critical thinkers, and innovative designers. To help them develop these skills, as a first step, it is essential to assess how to increase students\u27 awareness of engineering models. According to Bloom\u27s taxonomy, the lower remember and understand levels, which encompass awareness, are necessary for achieving the higher levels, such as apply, analyze, evaluate, and create. Research Questions: To what extent did student awareness of model types change after taking introductory engineering courses? To what extent did student awareness of model types differ by course or semester? Methodology: In this study, a survey was designed and administered at the beginning and end of the semester in two first-year engineering courses during two semesters in a mid-sized private school. The survey asked students questions about their definition of engineering modeling and different types of models. Findings: Overall, student awareness of model types increased from the beginning of the semester toward the end of the semester, across both semesters and courses. There were some differences between course sections, however, the students\u27 awareness of the models at the end of the academic year was similar for both groups

Informationの多変数解析への応用について

The Paleocene–Eocene Thermal Maximum (PETM), at ca. 55.8 Ma, is one of the most studied instances of past greenhouse gas-induced global warming. As such, it provides a rich opportunity to examine the impact of such global change on local climates. The effects of increased continental and sea surface temperatures on local precipitation and humidity during the PETM remain poorly constrained and studies reveal complex, regional differences; whilst some localities appear to experience a net increase in humidity, others exhibit the opposite. Crucially, there are few records of hydrological change from tropical regions. Recent onshore drilling expeditions in Tanzania have yielded expanded sedimentary sections, deposited in a marine environment, that span much of the Late Cretaceous and Paleogene and show exceptionally good preservation of both calcareous microfossils and organic matter. The PETM interval has previously been constrained by both biostratigraphy and carbon isotopic records and spans ca. 7 m of section. Lipid distributions, including various terrestrial, marine and bacterial biomarkers and their hydrogen isotopic compositions, as well as mineralogy, were used to examine East African vegetation and hydrological responses to the global change occurring at the PETM. Although total organic carbon contents decrease, the concentrations of both higher plant (n-alkanes, n-alkanoic acids) and soil bacterial (glycerol dialkyl glycerol tetraethers) biomarkers increase dramatically at the onset of the PETM negative carbon isotope excursion (CIE), suggesting an increased discharge of fluvial sedimentary organic matter. Similarly, mineralogical indicators of terrestrial input – including Ti/Al and Si/Al ratios, quartz contents and, notably, the proportion of kaolinite – also increase at the onset of the CIE. However, higher plant leaf wax n-alkanes (C27, C29 and C31) become more deuterium-enriched throughout the same interval, suggesting a more arid and/or hotter, rather than a more humid, environment. This evidence collectively suggests an East African early PETM climate characterised by overall hot and arid conditions punctuated by intense, perhaps seasonal, precipitation events. These data match observations from other locations at mid-latitudes, suggesting that the humid climate often suggested for the PETM was not globally widespread

3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (σ1) receptor

Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure–activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (r1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q2) regression value of 0.6, and a non-cross validatedr2 of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of atest set with an r2 >0.7. We also describe here the docking of the PCU-derivedcompounds into a homology model of the sigma-1 (r1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [3H]pentazocine binding assay anoxa-PCU, NGP1-01 (IC50 = 1.78 lM) and its phenethyl derivative (IC50 = 1.54 lM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(r1)Web of Scienc

Molecular Gas in the z=1.2 Ultraluminous Merger GOODS J123634.53+621241.3

We report the detection of CO(2-1) emission from the z=1.2 ultraluminous infrared galaxy (ULIRG) GOODS J123634.53+621241.3 (also known as the sub-millimeter galaxy GN26). These observations represent the first discovery of high-redshift CO emission using the new Combined Array for Research in Millimeter-Wave Astronomy (CARMA). Of all high-redshift (z>1) galaxies within the GOODS-North field, this source has the largest far-infrared (FIR) flux observed in the Spitzer 70um and 160um bands. The CO redshift confirms the optical identification of the source, and the bright CO(2-1) line suggests the presence of a large molecular gas reservoir of about 7x10^10 M(sun). The infrared-to-CO luminosity ratio of L(IR)/L'(CO) = 80+/-30 L(sun) (K Km/s pc^2)^-1 is slightly smaller than the average ratio found in local ULIRGs and high-redshift sub-millimeter galaxies. The short star-formation time scale of about 70 Myr is consistent with a starburst associated with the merger event and is much shorter than the time scales for spiral galaxies and estimates made for high-redshift galaxies selected on the basis of their B-z and z-K colors.Comment: Accepted for publication in ApJ Letter

Pathogenic germline MCM9 variants are rare in Australian Lynch-like syndrome patients

Lynch syndrome is a hereditary cancer syndrome caused by the autosomal dominant inheritance of loss-of-function mutations in DNA mismatch repair (MMR) genes. Approximately one quarter of clinically suspected cases have no identifiable germline mutation in any MMR gene, a condition known as Lynch-like syndrome (LLS). MCM9 was recently identified as the DNA helicase in the mammalian MMR complex and loss of helicase activity results in microsatellite instability. We hypothesized that pathogenic variants in MCM9 may account for LLS. The 5′UTR and coding region of MCM9 were sequenced in germline DNA of 109 Australian patients with LLS and variants were cross-referenced with three population-based databases (dbSNP144, 1000 Genomes, ExAC). The functional effect of variants was assessed in silico with PolyPhen-2, SIFT and CONDEL. Fifteen variants that included six common SNPs and nine variants of unknown significance (VUS) were identified. We conclude that VUS occur in MCM9 in a small proportion of LLS patients and MCM9 mutations are unlikely to explain most LLS cases

Transcriptional analysis of primary ciliary dyskinesia airway cells reveals a dedicated cilia glutathione pathway

Primary ciliary dyskinesia (PCD) is a genetic condition that results in dysmotile cilia. The repercussions of cilia dysmotility and gene variants on the multiciliated cell remain poorly understood. We used single-cell RNA-Seq, proteomics, and advanced microscopy to compare primary culture epithelial cells from patients with PCD, their heterozygous mothers, and healthy individuals, and we induced pluripotent stem cells (iPScs) generated from a patient with PCD. Transcriptomic analysis revealed unique signatures in PCD airway cells compared with their mothers\u27 cells and the cells of healthy individuals. Gene expression in heterozygous mothers\u27 cells diverged from both control and PCD cells, marked by increased inflammatory and cellular stress signatures. Primary and iPS-derived PCD multiciliated cells had increased expression of glutathione-S-transferases GSTA2 and GSTA1, as well as NRF2 target genes, accompanied by elevated levels of reactive oxygen species (ROS). Immunogold labeling in human cilia and proteomic analysis of the ciliated organism Chlamydomonas reinhardtii demonstrated that GSTA2 localizes to motile cilia. Loss of human GSTA2 and C. reinhardtii GSTA resulted in slowed cilia motility, pointing to local cilia regulatory roles. Our findings identify cellular responses unique to PCD variants and independent of environmental stress and uncover a dedicated ciliary GSTA2 pathway essential for normal motility that may be a therapeutic target

Brevi spunti sul d.lgs. n. 150/2009 e sulla sua applicabilità agli Enti locali

© 2014 Taylor & Francis Group, LLC. Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, CDH1 and CDKN2B, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent CDH1 silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.Link_to_subscribed_fulltex

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Novel opsin gene variation in large-bodied, diurnal lemurs

Some primate populations include both trichromatic and dichromatic (red-green colour blind) individuals due to allelic variation at the X-linked opsin locus. This polymorphic trichromacy is well described in day-active New World monkeys. Less is known about colour vision in Malagasy lemurs, but, unlike New World monkeys, only some day-active lemurs are polymorphic, while others are dichromatic. The evolutionary pressures underlying these differences in lemurs are unknown, but aspects of species ecology, including variation in activity pattern, are hypothesized to play a role. Limited data on X-linked opsin variation in lemurs make such hypotheses difficult to evaluate. We provide the first detailed examination of X-linked opsin variation across a lemur clade (Indriidae). We sequenced the X-linked opsin in the most strictly diurnal and largest extant lemur, Indri indri, and nine species of smaller, generally diurnal indriids (Propithecus). Although nocturnal Avahi (sister taxon to Propithecus) lacks a polymorphism, at least eight species of diurnal indriids have two or more X-linked opsin alleles. Four rainforest-living taxa-I. indri and the three largest Propithecus species-have alleles not previously documented in lemurs. Moreover, we identified at least three opsin alleles in Indri with peak spectral sensitivities similar to some New World monkeys