Leveraging best practices in data governance: An organization-wide data inventory and mapping project to support a five year data strategy

Introduction The professional regulation sector is moving toward risk-informed approaches that require high quality data. A key component of a corporate 2017 Data Strategy is the implementation of a data inventory and mapping project to catalogue, centralize, document and govern data assets that support regulatory decisions, programs and operations. Objectives and Approach In a data rich organization, the goals of the data inventory are to: enhance authoritative data that support programs; identify data duplications/gaps; identify data sources, owners and users; and, apply consistent data management and standards organizationally. Routinely used data assets outside the large enterprise workflow system (excel/word files; databases; paper collections) were catalogued. Using data governance principles and a facilitated questionnaire, departmental data stewards were interviewed about their generated data. Questions included data purpose/sources/types/formats/owners, retention rates, analytical products, gaps and visions for a desired data state. A data mapping methodology highlighted data set and variable connections within and across departments. Results To date, over 40 staff members in 10 departments were identified as data content experts. In addition to data in the corporate enterprise system, over 80 unique datasets were identified. In 1 large department, over 2,000 data elements across 26 datasets were inventoried. Data mapping analysis revealed thematic data domains, including member demographics, outcomes, certifications, tracking and financial data, collected and held in multiple formats ((Microsoft Access, Excel, Word), SPSS, PDF, e-mails and paper documents). While 72% of the data elements were formatted numerically, approximately 8% were free text. Significant data redundancies across staff members and departments were revealed, as well as unstandardized variable naming conventions. Gaps analysis highlighted need for standardized, electronic data, where not available and data management training. Conclusion/Implications Customized data mapping reports to data users will facilitate the development of local, standardized departmental data hubs that will centrally link to a centralized data repository to facilitate seamless organization-wide analytics, improvements in current data management practices and greater data collaboration with the ultimate goal of supporting risk-informed approaches

c-Fos Expression in the Nucleus of the Solitary Tract in Response to Salt Stimulation in Rats

Salt signals in tongue are relayed to the nucleus of the solitary tract (NST). This signaling is very important to determine whether to swallow salt-related nutrition or not and suggests some implications in discrimination of salt concentration. Salt concentration-dependent electrical responses in the chorda tympani and the NST were well reported. But salt concentration-dependency and spatial distribution of c-Fos in the NST were not well established. In the present study, NaCl signaling in the NST was studied in urethane-anesthetized rats. The c-Fos immunoreactivity in the six different NST areas along the rostral-caudal axis and six subregions in each of bilateral NST were compared between applications of distilled water and different concentrations of NaCl to the tongue of experimental animals. From this study, salt stimulation with high concentration (1.0 M NaCl) induced significantly higher c-Fos expression in intermediate NST and dorsal-medial and dorsal-middle subregions of the NST compared to distilled water stimulation. The result represents the specific spatial distribution of salt taste perception in the NST

Paramedic clinical decision making during high acuity emergency calls: design and methodology of a Delphi study

<p>Abstract</p> <p>Background</p> <p>The scope of practice of paramedics in Canada has steadily evolved to include increasingly complex interventions in the prehospital setting, which likely have repercussions on clinical outcome and patient safety. Clinical decision making has been evaluated in several health professions, but there is a paucity of work in this area on paramedics. This study will utilize the Delphi technique to establish consensus on the most important instances of paramedic clinical decision making during high acuity emergency calls, as they relate to clinical outcome and patient safety.</p> <p>Methods and design</p> <p>Participants in this multi-round survey study will be paramedic leaders and emergency medical services medical directors/physicians from across Canada. In the first round, participants will identify instances of clinical decision making they feel are important for patient outcome and safety. On the second round, the panel will rank each instance of clinical decision making in terms of its importance. On the third and potentially fourth round, participants will have the opportunity to revise the ranking they assigned to each instance of clinical decision making. Consensus will be considered achieved for the most important instances if 80% of the panel ranks it as important or extremely important. The most important instances of clinical decision making will be plotted on a process analysis map.</p> <p>Discussion</p> <p>The process analysis map that results from this Delphi study will enable the gaps in research, knowledge and practice to be identified.</p

Reproducibility of exhaled nitric oxide in smokers and non-smokers: relevance for longitudinal studies

<p>Abstract</p> <p>Background</p> <p>Currently, there is much interest in measuring fractional exhaled nitric oxide (<b>FE_NO</b>) in populations. We evaluated the reproducibility of <b>FE_NO</b>in healthy subjects and determined the number of subjects necessary to carry out a longitudinal survey of <b>FE_NO</b>in a population containing smokers and non-smokers, based on the assessed reproducibility.</p> <p>Methods</p> <p>The reproducibility of <b>FE_NO</b>was examined in 18 healthy smokers and 21 non-smokers. <b>FE_NO</b>was assessed once at 9 AM on five consecutive days; in the last day this measurement was repeated at 2 PM. Respiratory symptoms and medical history were assessed by questionnaire. The within- and between-session repeatability of <b>FE_NO</b>and log-transformed <b>FE_NO</b>was described. The power of a longitudinal study based on a relative increase in <b>FE_NO</b>was estimated using a bilateral t-test of the log-transformed <b>FE_NO</b>using the between-session variance of the assay.</p> <p>Results</p> <p><b>FE_NO</b>measurements were highly reproducible throughout the study. <b>FE_NO</b>was significantly higher in males than females regardless of smoking status. <b>FE_NO</b>was positively associated with height (p < 0.001), gender (p < 0.034), smoking (p < 0.0001) and percent FEV₁/FVC (p < 0.001) but not with age (p = 0.987). The between-session standard deviation was roughly constant on the log scale. Assuming the between-session standard deviation is equal to its longitudinal equivalent, either 111 or 29 subjects would be necessary to achieve an 80% power in detecting a 3% or a 10% increase in <b>FE_NO</b>respectively.</p> <p>Conclusion</p> <p>The good reproducibility of <b>FE_NO</b>is not influenced by gender or smoking habits. In a well controlled, longitudinal study it should allow detecting even small increases in <b>FE_NO</b>with a reasonable population size.</p

Factors affecting exhaled nitric oxide measurements: the effect of sex

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (F_ENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F_ENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F_ENO in a well characterised adult population.</p> <p>Methods</p> <p>Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F_ENO were explored by unadjusted and adjusted linear regression analyses.</p> <p>Results</p> <p>The effect of sex on F_ENO was both statistically and clinically significant, with F_ENO levels approximately 25% less in females. Overall, current smoking reduced F_ENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F_ENO measurement. Atopy increased F_ENO by 60%. The sex-related differences in F_ENO remained significant (p < 0.001) after controlling for all other significant factors affecting F_ENO.</p> <p>Conclusion</p> <p>Even after adjustment, F_ENO values are significantly different in males and females. The derivation of reference values and the interpretation of F_ENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.</p

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Differential Epigenetic Regulation of TOX Subfamily High Mobility Group Box Genes in Lung and Breast Cancers

Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment

Chromatin compaction in terminally differentiated avian blood cells: the role of linker histone H5 and non-histone protein MENT

Chromatin has a tendency to shift from a relatively decondensed (active) to condensed (inactive) state during cell differentiation due to interactions of specific architectural and/or regulatory proteins with DNA. A promotion of chromatin folding in terminally differentiated avian blood cells requires the presence of either histone H5 in erythrocytes or non-histone protein, myeloid and erythroid nuclear termination stage-specific protein (MENT), in white blood cells (lymphocytes and granulocytes). These highly abundant proteins assist in folding of nucleosome arrays and self-association of chromatin fibers into compacted chromatin structures. Here, we briefly review structural aspects and molecular mode of action by which these unrelated proteins can spread condensed chromatin to form inactivated regions in the genome

Molecular Epidemiology of HIV-1 Subtypes in India: Origin and Evolutionary History of the Predominant Subtype C

This thesis describes the translational genomics of HIV-1subtype C in India from its origin to therapeutic response with the aim to improve our knowledge for better therapeutic and preventive strategies to combat HIV/AIDS. In a systemic approach, we identified the molecular phylogeny of HIV-1 subtypes circulating in India and the time to most recent common ancestors (tMRCA) of predominant HIV-1 subtype C strains. Additionally, this thesis also studied drug resistance mutations in children, adolescents and adults, the role of host factors in evolution of drug resistance, and population dynamics of viremia and viral co-receptor tropism in perinatal transmission. Finally, the long term therapeutic responses on Indian national first-line antiretroviral therapy were also studied. In Paper I, we reported an increase in the HIV-1 recombinant forms in the HIV-1 epidemiology using a robust subtyping methodology. While the study confirmed HIV- 1 subtype C as a dominant subtype, its origin was dated back to the early 1970s from a single or few genetically related strains from South Africa, whereafter, it has evolved independently. In Paper II, the lethal hypermutations due to the activity of human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (hA3G) was significantly associated with antiretroviral therapy (ART) failure in Indian HIV-1 subtype C patients. The presence of M184I and M230I mutations were observed due to the editing of hA3G in the proviral compartment but stop codons were also found in the open reading frames and the same drug resistance mutations were absent in plasma virus. Therefore, it is unlikely that the viral variants which exhibit hypermutated sequences and M184I and/or M230I will mature and expand in vivo and hence are unlikely to have any clinical significance. The high concordance of drug resistance genotyping in the plasma and proviral compartments in therapy-naïve patients, gives weight to the idea of using whole blood for surveillance of drug resistance mutations which precludes logistic challenges of cold chain transport. In Papers III and IV, we identified a substantial proportion of HIV-1 subtype C perinatally-infected older children who had a high burden of plasma viremia but also had high CD4+ T-cell counts. In addition, older children with HIV-1 subtype C infection presented a high prevalence of predicted X4 and R5/X4 tropic strains which indicates that HIV-1 subtype C strains required longer duration of infection and greater disease progression to co-receptor transition from R5- to X4-tropic strains (IV). Our studies also indicate that transmitted drug resistance is low among Indian HIV-1 infected children, adolescents (III) and adults (II). In Paper V, in a longitudinal cohort study, a good long-term response to the Indian national first-line therapy for a median of nearly four years with 2.8% viral failure, indicating the overall success of the Indian ART program. Our study also showed that three immunologically well patients with virological rebound and major viral drug resistance mutations (M184V, K103N and Y181C) during one study visit had undetectable viral load at their next visit. These findings suggest that use of multiple parameters like patients’ immunological (CD4+ T-cell count), virological (viral load) and drug resistance data should all be used to optimize the treatment switch to second line therapy. In conclusion, this translational genomics study enhances our knowledge about the HIV-1 subtype C strains circulating in India which are genetically distinct from prototype African subtype C strains. Considerably more research using appropriate models need to be performed to understand the phenotypic and biological characteristics of these strains to guide efficient disease intervention and management strategies