Exploring data quality monitoring procedures in the clinical research setting: Insights from clinical studies

To learn about human health, clinical research studies are conducted. A substantial concern for all clinical research studies is the failure to collect, process and present good quality data. Poor data quality may stem from error. International guidelines have identified that it is an essential need to monitor study activity to ensure that the rights, safety and wellbeing of participants are protected. However, the guidelines provide limited insight on how to perform monitoring procedures including the nature and extent of monitoring needed to ensure quality. Without clear guidance, this leaves clinical researchers confused about the most appropriate quality assurance and control procedures. The central hypothesis of this thesis is that despite the wide variations, exploration and evaluation of appropriate data quality monitoring procedures in clinical research studies will provide guidance toward developing a “fit-for-use” data quality monitoring framework (DQMF). This hypothesis was tested in five key studies using an explanatory sequential design guided by the Data- Information-Knowledge-Wisdom (DIKW) model as the theoretical framework

Nutrient Uptake and Management Strategies in Recirculating Hydroponic Systems

Nutrient management in recirculating hydroponic systems requires the periodic replenishment of water and nutrients to the nutrient solution reservoir. Common nutrient management strategies, such as replenishing the reservoir with fresh solution and maintaining a constant solution electrical conductivity (EC), can lead to ion accumulation and nutrient imbalances since nutrients are taken up by roots and depleted from solution at different rates. To avoid nutritional disorders, commercial growers typically dump and replace the hydroponic solution periodically, which is wasteful and has an economic cost. A potential alternative is to specially formulate the nutrient replenishment solution to balance the supply of nutrients with the uptake of nutrients into plant tissues. As a result, nutrients would be consistently replaced in solution at a rate similar to the uptake by plant roots. A range of published nutrient solution formulations for hydroponic leafy greens crops were reviewed and shown to vary considerably in nutrient concentrations, many of which would be expected to oversupply certain nutrients, particularly calcium, magnesium, and sulfur. A study was conducted to quantify nutrient uptake and water use efficiency (WUE) by arugula (Eruca sativa L.) and basil (Ocimum basilicum L.) and determine if the strategy for replenishing nutrients impacted plant growth and nutrient uptake. A second study evaluated the potential to design a species-specific replenishment solution for arugula and basil to minimize the accumulation of ions in solution over time. Overall, arugula and basil differed in plant growth, uptake of individual nutrients, and transpiration, but were similar in WUE. Nutrient replenishment strategy had minimal to no impacts on plant growth, nutrient uptake, or WUE. Similarly, species-specific replenishment solutions formulated for arugula and basil had minimal effects on plant growth, nutrient uptake into plant tissues, or WUE when compared to nutrient replenishment with a standard hydroponic solution used commercially. Species-specific replenishment solutions also decreased the accumulation of nutrient ions, particularly calcium, magnesium, and sulfate, compared to a standard hydroponic replenishment solution. For both arugula and basil, solution EC increased when nutrients were replenished with the commercial standard solution, but remained more stable when nutrients were replaced using the species-specific replenishment solutions. Species-specific replenishment solutions may be a strategy for growers to prevent salt accumulation and ion imbalances in recirculating hydroponic systems, minimizing the risk of nutritional disorders and the need to dump and replace solution. Since species-specific replenishment strategies reduced changes in solution EC over time, this approach would improve the practice of managing nutrient supply by maintaining a target EC level. Growers can develop their own species-specific replenishment solutions by monitoring plant uptake of nutrients, growth and yield, and water use during production

Perceived Barriers to Including Students with Visual Impairments in General Physical Education

The purpose of this study was to examine barriers perceived by teachers when including students with visual impairments in general physical education. Teachers (52 males, 96 females) who had children with visual impairments in their physical education classes were surveyed prior to in-service workshop participation. The most prevalent barriers were professional preparation, equipment, programming, and time. A logistic regression analysis, regressing gender, in-service training, number of students with visual impairments taught, masters degree attained, masters hours spent on visual impairments (yes or no), undergraduate hours spent on visual impairments (yes or no), and years of experience failed to indicate significant predictors of professional preparation as a barrier, Model x2 (6, n = 148) = 4.48, p \u3e .05

Individualized Education Plan Applied to Physical Education: Validation of Inventory in Portuguese Version

From specific needs of the countries of origin, an inventory called "Individualized Education Plan applied to Physical Education" (IEP-PE) was developed through international collaboration by faculty researchers from North and South America. Versionsin English, Spanish and Portuguese are being simultaneously validated. This essay aims to validate the Portuguese version of the Individualized Education Plan (IEP-PE) specifically designed for the area of physical education, in order to direct the planning of actions in this context. This is an exploratory study involving content validation of the IEP-PE. The invitation letter and the criteria for their validation of the instrument were sent to 10 Brazilian judges. Validated Portuguese version of IEP-PE, as well as the adjustments arising from the analysis of the judges, will be presented in this article

β-Turn sequences promote stability of peptide substrates for kinases within the cytosolic environment

A strategy was developed to extend the lifetime of an peptide-based substrate for Abl kinase in the cytosolic environment. Small β-turn structures were added to the peptide’s N-terminus to block entry into peptidase catalytic sites. The influence of the size of the β-turn and two covalent cross-linking strategies on the rate of hydrolysis was assessed. The most peptidase-resistant substrate was degraded at a rate of 0.6 pmol mg−1 s−1 and possessed a half-life of 20.3 ± 1.7 min in a Baf/BCR-ABL cytosolic lysate, representing 16- and 40-fold improvements, respectively, over that of a control peptide lacking the β-turn structure. Furthermore, the kcat/KM value of this peptide was 432 μM−1 min−1, a 1.25X increase over the unmodified control, verifying that the added β-turn did not hinder the substrate properties of the peptide. This improved peptide was microinjected into single Baf/BCR-ABL cells and substrate phosphorylation measured. Zero to forty percent of the peptide was phosphorylated in the single cells. In contrast, when the control peptide without a β-turn was loaded into cells, the peptide was too rapidly degraded to detect phosphorylation. This work demonstrates that small β-turn structures can render peptides more resistant to hydrolysis while retaining substrate efficacy and shows that these stabilized peptides have the potential to be of high utility in single-cell enzyme assays

The PrPC Cl fragment derived from the ovine A(136)R(154)R(171) PRNP allele is highly abundant in sheep brain and inhibits fibrillisation of full-length PrPC protein in vitro

AbstractExpression of the cellular prion protein (PrPC) is crucial for the development of prion diseases. Resistance to prion diseases can result from reduced availability of the prion protein or from amino acid changes in the prion protein sequence. We propose here that increased production of a natural PrP α-cleavage fragment, C1, is also associated with resistance to disease. We show, in brain tissue, that ARR homozygous sheep, associated with resistance to disease, produced PrPC comprised of 25% more C1 fragment than PrPC from the disease-susceptible ARQ homozygous and highly susceptible VRQ homozygous animals. Only the C1 fragment derived from the ARR allele inhibits in-vitro fibrillisation of other allelic PrPC variants. We propose that the increased α-cleavage of ovine ARR PrPC contributes to a dominant negative effect of this polymorphism on disease susceptibility. Furthermore, the significant reduction in PrPC β-cleavage product C2 in sheep of the ARR/ARR genotype compared to ARQ/ARQ and VRQ/VRQ genotypes, may add to the complexity of genetic determinants of prion disease susceptibility

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN