43 research outputs found
Parental mental health, parenting behaviours and the quality of life of children with cancer.
Two central themes were assessed in this thesis involving children with cancer.
First, the relationship between the child's medical functioning and their overall
quality of life (QOL). Second, how the child's illness and subsequent QOL related
to parental mental health and parenting behaviours. These themes were explored
using the Risk and Resilience model developed by Wallander et al. (1989b).
Study one involved children diagnosed with acute lymphoblastic leukaemia
(ALL), the most common form of childhood cancer. Results showed that the
child's medical functioning (e.g., time since diagnosis) did not relate to the child's
QOL, but did relate to parental mental health. Furthermore, child QOL was
significantly related to both parental mental health (depression) and parenting
behaviours (endorsement of force).
In an attempt to explore these themes in greater detail, Study two involved two
groups of cancer survivors, those with ALL or tumours of the central nervous
system (CNS). Medically, these groups have different prognoses, treatments, and
long-term consequences. Results showed that those with poorer medical
functioning, i.e., CNS tumours, had poorer QOL than both the ALL group and
population norms, confirming the relationship between the child's medical and
psychological adaptation. Furthermore, the child's adaptation was strongly related
to both parental mental health and parenting behaviours, again providing evidence
for the relationship between child and parent functioning.
The results of both studies in this thesis go some way to demonstrate the wide-ranging
effects that cancer can have on both the child and family. The child's
QOL can be compromised by the illness. Moreover, cancer has a detrimental
effect on the family life, from pervasive feelings of depression and worry, to longterm
concerns about child-rearing. This thesis has shown that those children with
CNS involvement, and their families, are particularly at-risk. To conclude, a
section outlining clinical interventions which can help reduced the impact of
childhood cancer on the family are discussed
Exploring Expat-preneur Similarities and Differences between Self-initiated and Company-Assigned Transitioned Expatriates
Based upon the authors’ collective international experience and observance of emerging trends, this paper explores two different types of expat-preneurs as a new growing international career phenomenon: self-initiated expatriate expat-preneurs and company-assigned expatriate transitioned expat-preneurs. While the former is comprised of entrepreneurs who initiate their own expatriation to a new host country, the latter refers to expatriates who, during or at the end of a traditional international expatriate assignment, have started their own transition away from multinational organizations and into an entrepreneurial career in the host country or region of residence. This paper first summarizes the backgrounds and development patterns of these two distinctive types of expat-preneurs. It discusses similarities and differences between the two groups and suggests research propositions in terms of their approach to identifying business opportunities, meeting contextual conditions, and other characteristics. Finally, the paper discusses important implications and potential future research directions
Comparison of Three Targeted Enrichment Strategies on the SOLiD Sequencing Platform
Despite the ever-increasing throughput and steadily decreasing cost of next
generation sequencing (NGS), whole genome sequencing of humans is still not a
viable option for the majority of genetics laboratories. This is particularly
true in the case of complex disease studies, where large sample sets are often
required to achieve adequate statistical power. To fully leverage the potential
of NGS technology on large sample sets, several methods have been developed to
selectively enrich for regions of interest. Enrichment reduces both monetary and
computational costs compared to whole genome sequencing, while allowing
researchers to take advantage of NGS throughput. Several targeted enrichment
approaches are currently available, including molecular inversion probe ligation
sequencing (MIPS), oligonucleotide hybridization based approaches, and PCR-based
strategies. To assess how these methods performed when used in conjunction with
the ABI SOLID3+, we investigated three enrichment techniques: Nimblegen
oligonucleotide hybridization array-based capture; Agilent SureSelect
oligonucleotide hybridization solution-based capture; and Raindance
Technologies' multiplexed PCR-based approach. Target regions were selected
from exons and evolutionarily conserved areas throughout the human genome. Probe
and primer pair design was carried out for all three methods using their
respective informatics pipelines. In all, approximately 0.8 Mb of target space
was identical for all 3 methods. SOLiD sequencing results were analyzed for
several metrics, including consistency of coverage depth across samples,
on-target versus off-target efficiency, allelic bias, and genotype concordance
with array-based genotyping data. Agilent SureSelect exhibited superior
on-target efficiency and correlation of read depths across samples. Nimblegen
performance was similar at read depths at 20× and below. Both Raindance
and Nimblegen SeqCap exhibited tighter distributions of read depth around the
mean, but both suffered from lower on-target efficiency in our experiments.
Raindance demonstrated the highest versatility in assay design
2009- 2010 UNLV McNair Journal
Journal articles based on research conducted by undergraduate students in the McNair Scholars Program
Table of Contents
Biography of Dr. Ronald E. McNair
Statements:
Dr. Neal J. Smatresk, UNLV President
Dr. Juanita P. Fain, Vice President of Student Affairs
Dr. William W. Sullivan, Associate Vice President for Retention and Outreach
Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach
McNair Scholars Institute Staf
Community as an Institutional Learning Goal at the Unversity of Dayton
This working paper summarizes the work of the Habits of Inquiry and Reflection Community Fellows. It considers the meaning of community both in UD’s historic mission and in the ways it is practiced at UD now; identifies obstacles and failures; and offers recommendations for advancing community as a learning goal at UD
Intestinal Inflammation Responds to Microbial Tissue Load Independent of Pathogen/Non-Pathogen Discrimination
The intestinal immune system mounts inflammatory responses to pathogens but tolerates harmless commensal microbiota. Various mechanisms for pathogen/non-pathogen discrimination have been proposed but their general relevance for inflammation control is unclear. Here, we compared intestinal responses to pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered intestinal Peyer’s patches and, surprisingly, induced qualitatively and quantitatively similar initial inflammatory responses revealing a striking discrimination failure. Diverging inflammatory responses only occurred when Salmonella subsequently proliferated and induced escalating neutrophil infiltration, while harmless E. coli was rapidly cleared from the tissue and inflammation resolved. Transient intestinal inflammation induced by harmless E. coli tolerized against subsequent exposure thereby preventing chronic inflammation during repeated exposure. These data revealed a striking failure of the intestinal immune system to discriminate pathogens from harmless microbes based on distinct molecular signatures. Instead, appropriate intestinal responses to gut microbiota might be ensured by immediate inflammatory responses to any rise in microbial tissue loads, and desensitization after bacterial clearance
REPORT Whole-Exome Sequencing Links a Variant in DHDDS to Retinitis Pigmentosa
Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions. Retinitis pigmentosa (RP) refers to a large group of genetically heterogeneous retinal degenerative disorders characterized by early rod photoreceptor dysfunction followed by progressive rod and cone photoreceptor dysfunction and photoreceptor death (MIM 268000). Impaired night vision followed by impaired peripheral vision generally starts in adolescence to young adulthood, with subsequent impaired central vision in later life. We studied a family of Ashkenazi Jewish (AJ) origin in which three out of four siblings (two females and one male) were diagnosed with RP in their teenage years ( To identify the genetic cause of this likely recessive subtype of RP, we screened all genes known to harbor RP mutations and found that they were negative for mutations. Classic linkage approaches were not applicable because of the size of the nonconsanguineous family, so we performed whole-exome sequencing in the three affected siblings and one unaffected sibling (Whole Human Exome Capture kit, Roche). We produced approximately 10 gigabases (Gb) of paired-end 75 bp sequence reads per individual on the Illumina GAII platform. To test the overall quality of the sequence data, we compared the genotypes of variants found in the sequence data to variants derived from genotyping via a genome-wide SN
Identifying Consensus Disease Pathways in Parkinson's Disease Using an Integrative Systems Biology Approach
Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD
Activation Mobilizes the Cholesterol in the Late Endosomes-Lysosomes of Niemann Pick Type C Cells
A variety of intercalating amphipaths increase the chemical activity of plasma membrane cholesterol. To test whether intracellular cholesterol can be similarly activated, we examined NPC1 and NPC2 fibroblasts, since they accumulate large amounts of cholesterol in their late endosomes and lysosomes (LE/L). We gauged the mobility of intracellular sterol from its appearance at the surface of the intact cells, as determined by its susceptibility to cholesterol oxidase and its isotope exchange with extracellular 2-(hydroxypropyl)-β-cyclodextrin-cholesterol. The entire cytoplasmic cholesterol pool in these cells was mobile, exchanging with the plasma membrane with an apparent half-time of ∼3–4 hours, ∼4–5 times slower than that for wild type human fibroblasts (half-time ∼0.75 hours). The mobility of the intracellular cholesterol was increased by the membrane-intercalating amphipaths chlorpromazine and 1-octanol. Chlorpromazine also promoted the net transfer of LE/L cholesterol to serum and cyclodextrin. Surprisingly, the mobility of LE/L cholesterol was greatly stimulated by treating intact NPC cells with glutaraldehyde or formaldehyde. Similar effects were seen with wild type fibroblasts in which the LE/L cholesterol pool had been expanded using U18666A. We also showed that the cholesterol in the intracellular membranes of fixed wild-type fibroblasts was mobile; it was rapidly oxidized by cholesterol oxidase and was rapidly replenished by exogenous sterol. We conclude that a) the cholesterol in NPC cells can exit the LE/L (and the extensive membranous inclusions therein) over a few hours; b) this mobility is stimulated by the activation of the cholesterol with intercalating amphipaths; c) intracellular cholesterol is even more mobile in fixed cells; and d) amphipaths that activate cholesterol might be useful in treating NPC disease
Behavior and chronic toxicity of two differently stabilized silver nanoparticles to Daphnia magna
While differences in silver nanoparticle (AgNP) colloidal stability, surface potential, or acute aquatic toxicity for differently stabilized AgNP have often been reported, these have rarely been studied in long-term ecotoxicity tests. In the current study, we investigated the chronic toxicity of AgNP to Daphnia magna over a 21-day period with two different stabilizers (citrate and detergent), representative for charge and sterical stabilizers, respectively. This was coupled with a series of short-term experiments, such as mass balance and uptake/depuration testing, to investigate the behavior of both types of AgNP during a typical media exchange period in the D. magna test for chronic toxicity. As expected, the sterically stabilized AgNP were more stable in the test medium, also in the presence of food; however, a higher uptake of silver after 24 h exposure of the charge stabilized AgNP was found compared to the detergent-stabilized AgNP (0.046 ± 0.006 μg Ag μg DW−1 and 0.023 ± 0.005 μg Ag μg DW−1, respectively). In accordance with this, the higher reproductive effects and mortality were found for the charge-stabilized than for the sterically-stabilized silver nanoparticles in 21-d tests for chronic toxicity. LOEC was 19.2 μg Ag L−1 for both endpoints for citrate-coated AgNP and >27.5 μg Ag L−1 (highest tested concentration for detergent-stabilized AgNP). This indicates a link between uptake and toxicity. The inclusion of additional short-term experiments on uptake and depuration is recommended when longer-term chronic experiments with nanoparticles are conducted