Genotoxic effects such as mutations and chromosome abnormalities can augment the risk of adverse health effects such as cancer and heritable genetic diseases; chemicals in commerce must be screened for genotoxic activity. To this end, Toxys B.V. developed the in vitro ToxTracker® assay, which detects (geno)toxicity by monitoring the activity of six reporter genes in cultured mES cells (murine embryonic stem cells), i.e., Rtkn, Bscl2, Btg2, Srxn1, Blvrb and Ddit3. The reporters respond to genotoxic stress, oxidative stress, and endoplasmic reticulum stress characterized by protein unfolding; reporter induction is monitored using flow cytometry. The ToxTracker® assay generates large amounts of multivariate concentration-response data; this study employed innovative quantitative methods to scrutinize ToxTracker® assay results. The work (i) defined a fold-change threshold for identification of a significant positive response, (ii) used two analytical approaches to define endpoint-specific Benchmark Response (BMR) values, (iii) used the BMD (Benchmark Dose) combined-covariate approach for potency ranking of assay validation compounds, and (iv) used PCA (Principal Component Analysis) to investigate functional and statistical relationships between the reporters. The results revealed fold-change cut-offs of 1.5 and 1.7 for identification of weak and strong positive responses, respectively. 1.5-fold is consistent with the value advocated by Toxys B.V.; 1.7-fold is more conservative than the Toxys-advocated 2-fold value. Potency ranking of the validation compounds permitted comparative identification of the most potent inducers of each reporter. The most potent compounds consistently included clastogens used for cancer chemotherapy. BMR values determined using the Zeller et al. (2017) approach ranged from 2.2% for Blvrb and Rtkn, to 7.0% for Ddit3, with an average of 3.9% across all the reporters. The Slob (2016) approach yielded values that ranged from 30% for Ddit3, to 52% for Rtkn, with an average of 43%. The PCA results indicated the Rtkn, Bscl2 and Btg2 reporters are functionally redundant; collectively indicative of genotoxic stress. The Blvrb and Ddit3 reporters are orthogonal indicators of oxidative stress and protein unfolding, respectively; they are essential for toxicological profiling using the ToxTracker® assay. PCA axis scores reflect the toxicological MOA (Mode of Action) of the tested compounds; hitherto unknown MOAs can be inferred using PCA axis-plot proximity to well-studied compounds. Like most in vitro (geno)toxicity assessment assays, ToxTracker® employs a material known as S9 to simulate mammalian hepatic metabolism. S9 is prepared from the livers of rats exposed to an inducer of microsomal CYP (Cytochrome P450) isozymes; the most common CYP inducer is the PCB (polychlorinated biphenyl) mixture known as Aroclor-1254. Due to restrictions in the availability of Aroclor-1254, this study also evaluated the utility of Phenobarbital (PB)/β-Naphthoflavone (BNF)-induced S9, a proposed substitute for Aroclor-induced S9. The results indicate that, despite differences in enzymatic profiles, a 24-hr protocol using 0.40% v/v PB/BNF-induced S9 yields results that are comparable to those obtained using 0.25% v/v Aroclor-induced S9. This study constitutes a significant step towards augmenting the utility of the ToxTracker® assay; it provides a foundation for eventual adoption of high-throughput reporter assays for routine regulatory screening of new and existing chemicals.

Magister Pharmaceuticae - MPharm / Diabetes mellitus is a complex chronic condition and has become a major public health concern worldwide. Many diabetic patients are accessing primary health care (PHC) clinics for diabetes care. Diabetic patients who are considered stable are referred to chronic diseases of lifestyle club at the PHC facility. Effective management of this chronic condition requires a multidisciplinary team approach to diabetes care. Pharmacists are not often included in a multidisciplinary team and would consist of doctors, nurses and dieticians. Teams may be expanded and require specialist healthcare members’ expertise who can assist in the management of this disease, for example, ophthalmologists and podiatrists. Adherence to standard treatment guidelines (STGs) for the management of diabetes by healthcare professionals at a primary care level can improve glycemic control, decrease health costs and reduce the development of long-term diabetic complications.

Les industries de traitement du phosphate dans le but de produire des engrais phosphatés, très présentes dans la zone côtière sud du Grand Sfax en Tunisie, sont à l’origine d’émissions atmosphériques et de rejets de déchets ; en l’occurrence du phosphogypse chargés de contaminants métalliques. La contamination des sols qui en résulte est une contamination persistante. Dans le but de mieux comprendre les effets de la contamination par les métaux engendrés par cette activité industrielle, une attention particulière a été portée sur une espèce d’importance économique, le palmier dattier Phoenix dactylifera. Le présent travail avait pour objectifs d'étudier la germination des graines et la variété Deglet Nour dans différents contextes de contamination métallique aux moyens de techniques de biotechnologie végétale impliquant la recherche in silico et la culture in vitro de vitroplant et à l’aide de deux approches. Une approche individuelle intégrative qui s’est servie de nombreuses mesures de biomarqueurs morphologiques et biochimiques chez l’espèce étudiée exposée à divers stress métalliques. Une deuxième approche, plus moléculaire et mécanistique avait pour but d’identifier des gènes qui répondent à une exposition au Cd, ou au Cu, ou au Cr capables de prédire les voies métaboliques impliquées. Cette seconde approche, basée sur l’exploitation d’une banque de cDNA de la variété Deglet Nour a permis l’identification de gènes de chélateurs et transporteurs de métaux. Le suivi des niveaux d’expression de ces gènes chez des plantes placées dans des conditions d’expositions métalliques variées a permis de mieux comprendre les mécanismes de détoxication des métaux mis en œuvre. / The phosphate processing industries for the production of phosphate fertilizers, which are present in the southern coastal zone of the Grand Sfax in Tunisia, caused atmospheric emissions and waste discharges i.e., phosphogypsum loaded with metal contaminants. The resulting contamination of soils is a persistent contamination. In order to better understand the effects of metal contamination caused by this industrial activity and ultimately to propose measures for the rehabilitation and/or ecological restoration of the sites but also because of its economic importance, particular attention has been paid on the palm date (Phoenix dactylifera). The aim of this work was to study seed germination and growth of the Deglet Nour variety in various metal contamination contexts by means of plant biotechnology techniques involving in silico research and in vitro culture of vitroplant. Two approaches have been performed. An individual integrative approach that used numerous measurements of morphological and biochemical biomarkers in date palm exposed to various metal stresses. A second approach, more molecular and mechanistic, was performed to identify genes that respond when plants are exposed to Cd, Cu, or Cr which help for the prediction of the metabolic pathways that are affected by contaminants or involved in detoxification processes. This second approach, based on the exploitation of a cDNA library of the Deglet Nour variety, allowed the identification of genes coding for metal chelators and transporters. Monitoring of the levels of expression of these genes made it possible to better understand the detoxification mechanisms of metals in the palm date.

Narcissistic transformation leaders have inflicted severe physical, psychological, and financial damage on individuals, institutions, and society. Multifactor Leadership Questionnaire (MLQ) has shown promise for early detection of narcissistic leadership tendencies, but selection criteria have not been established. The purpose of this quantitative research was to determine if item response theory (IRT) could advance the detection of narcissistic leadership tendencies using an item-level analysis of the 20 transformational leadership items of the MLQ. Three archival samples of subordinates from Israeli corporate and athletic organizations were combined (N = 1,703) to assess IRT data assumptions, comparative fit of competing IRT models, item discrimination and difficulty, and theta reliabilities within the trait range. Compared to the generalized graded unfolding model, the graded response model had slightly more category points within the 95% confidence interval and consistently lower X2/df item fit indices. Items tended to be easier yet more discriminating than average, and five items were identified as candidates for modification. IRT item marginal reliability was .94 (slightly better than classical test theory reliability of .93), and IRT ability prediction had a .96 reliability within a trait range from -1.7 to 1.3 theta. Based on 8 invariant item parameters, selection criteria of category fairly often (3) or above on attributed idealized influence items and sometimes (2) or below on individual consideration items was suggested. A test case demonstrated how narcissistic tendencies could be detected with these criteria. The study can contribute to positive social change by informing improved selection processes that more effectively screen candidates for key leadership roles that directly impact the wellbeing of individuals and organizations.

The importance of good communications between team members has been well documented. Yet previous studies on communications between team members have neglected to focus on reasons for information withholding between people working on teams. The purpose of this case study of 16 engineers and 6 educators was to understand why team members withhold information when working together. A convenience sample was selected from a software engineering organization. Collective intelligence theory in a modern communications environment was used as the theoretical foundation. This theory posits that the synergy of full group collaboration results in enhanced performance and the spread of new ideas. The exploratory research questions addressed in this study were designed to understand how employees decide what information to withhold when participating on teams; how withholding information is influenced by critical thinking, creativity, positions on a team, and type of employee; and the effects of information withholding. Collected data from online interviews were transcribed and validated via member checks, coded using open and axial coding, and analyzed. Seven themes were found: insecurity, gate keeping, discrimination, personality, creativity, organizational structure, and team management. The results of this study may provide information that can help managers understand employees' experiences with, reactions to, and opinions about information withholding and provide strategies to create an environment in which team members do not withhold information from each other, thus improving or enhancing positive social change in organizations.

Attention-deficit/hyperactivity disorder (ADHD) diagnosed during childhood can continue into adulthood, but most research on the topic has been done on children and adolescents. This research focus has thus often left out the population of adults with this disorder. In particular, there is little research on the role that self-regulation plays in the lives of adults on several life domains, especially in the workplace. The purpose of this qualitative, phenomenological study was to understand the role that self-regulation plays in the occupational functioning of adults with ADHD. Self-regulation theory provided the tenets that were used to examine how adults with ADHD self-regulate their emotions in the occupational setting. A modified version of the Stevick-Colaizzi-Keen method of analysis of phenomenological data was used to analyze transcripts of participant interviews with 11 Adults who have an ADHD diagnosis and at least one year of work experience. The results showed that many of the participants had difficulty with self-regulation, particularly with effectively managing the situation by considering the long-term consequences for their actions. The study has several social change implications. First, the findings might add to scholarly literature regarding the later-life impact of adult ADHD, enabling such changes as additional treatment of ADHD in adulthood and potential accommodations, support, and training on the job. Given the centrality of employment issues in the life of an adult, the findings may provide direction and insight to employers in managing employees with ADHD, making them more productive members of the workplace.

Parenting can be very challenging, especially when raising a disabled child. Children with disabilities require more supports and are more likely to be abused. The parent-child relationship is an important factor in ensuring child welfare. Little research has focused on identifying the impact of parenting characteristics on raising a child with a disability. The purpose of this study was to examine whether parenting style, parenting competence, and parenting stress were predictors of parent-child relationship quality in parents of children with disabilities ages 3 to 12 years. This study was quantitative and used multiple linear regression to identify predictor variables of the quality of the parent-child relationship. A convenience sample of 244 parents identified through a Qualtrics participant pool completed online surveys. Minuchin's structural family theory was used to guide this research and identify how challenges, such as raising a child with a disability, can cause distress when families are unable to adapt and parents are unable to maintain authority. Parenting factors were assessed using the Parenting Stress Index-4 Competence subscale, the Parenting Stress Index-4 SF, and the Parenting Styles and Dimensions Questionnaire. The quality of the parent-child relationship was assessed using the Parent-Child Relationship Inventory. The results of this study indicated that all parenting factors examined were significant predictors of the parent-child relationship quality. Age of the child was not a predictor. These findings have positive social change implications and can be used to increase practitioner knowledge of the impact of these parenting characteristics on parent-child relationship quality. Modification of treatment models could improve parenting behaviors, reduce parental stress and incidents of child abuse, and assess for the most conducive parenting styles for raising a disabled child.

The purpose of the study is to fill the gap in the literature regarding sibling bereavement. This study explored how sibling bereavement from unnatural causes of death affects surviving siblings. Bereavement affects millions of Americans every year. Most grieve naturally, but some experience complicated grief or depression. Many studies address parental and spousal bereavement, but few focus on sibling bereavement. This study fills that gap in the literature so that mental health care professionals and the general public understand what bereaved siblings experience after the death of a sibling. The study was a phenomenological study using social constructivism as a theoretical lens to explore how sibling bereavement affects surviving siblings. Open-ended interviews were collected from 10 bereaved siblings. Those interviews were then transcribed and categorized using a 7 step process to review and organize all relevant statements. Results of this study shows that sibling bereavement can be a life changing event for surviving siblings affecting all aspects of life and leaving unanswered questions and feelings of guilt. Participants also state they felt overlooked after the death leading to delayed grief. Participants concluded that sibling grief is subjective, so any treatment plan should be catered to the individual based on their relationship to the deceased sibling and the role the sibling played. This study can bring about positive social change by helping mental health care workers understand sibling bereavement better so that they may help those suffering from complicated grief following the loss of a sibling.

Pre-harvest contamination of maize grain with aflatoxin is a chronic problem worldwide and particularly in the southeastern U.S. Aflatoxin is a mycotoxin produced by the fungus Aspergillus flavus, an opportunistic ear-rot pathogen of maize (Zea mays). Resistance to aflatoxin accumulation is heritable, and resistant germplasm-lines are available. These lines are derived from “exotic” genetic backgrounds and were released as sources of resistance, not parental inbreds. However, all current sources of resistance are quantitative, which complicates conventional efforts to introgress resistance alleles from unadapted but resistant donor lines to adapted but susceptible recipient lines. Mapping quantitative trait loci (QTL) and their linked markers enables targeted introgression of the desired alleles via marker-assisted selection. Quantitative trait loci were identified in two F2:3 mapping populations, derived from crossing resistant inbreds Mp715 and Mp717 to a common susceptible parent (Va35). The Mp715 x Va35 population was phenotyped for aflatoxin accumulation under artificial inoculation in replicated field trials at Mississippi State (MSU) in 2015 and 2016. The Mp717 x Va35 population was phenotyped at MSU and Lubbock, TX in 2016. Populations were genotyped using simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers and linkage maps created in JoinMap4. To locate QTL, linkage maps, genotypes, and phenotypes were analyzed jointly in QTL Cartographer 2.5 using composite interval mapping (CIM) and multiple interval mapping (MIM) procedures. Five QTL with the beneficial allele contributed by Mp715 were identified during CIM in bins 5.01, 6.06, 7.03 10.04 and 10.05. Three QTL with the beneficial allele contributed by Mp717 were identified during CIM in bins 3.07/3.08, 7.02/7.03, and 10.05. In both populations, QTL were identified with the beneficial allele contributed by Va35. Those QTL did not co-locate across populations but four of the six were on chromosome 1. Significant QTL effects from CIM were used as the initial model terms in MIM, where all QTL effects were fit simultaneously and their gene-action and epistatic interactions estimated.

No description available.