948 resultados para Significant Structure
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The deployment of flat concrete blocks on subtidal rocky reefs can replicate natural reef microhabitats and provides a means for standardized sampling of cryptic invertebrates. The shape of the cavity beneath the block is related to reef topography and may influence the invertebrate community by affecting the amount of space for cryptic fauna to colonise and influencing the effectiveness of their predator-defence mechanisms. To determine the effect of sub-block reef structure and different levels of external predators on cryptic molluscs and echinoderms, I deployed concrete blocks at locations inside and outside the Maria Island marine reserve in eastern Tasmania, Australia. Relationships between sub-block reef structure and the cryptic invertebrate assemblage were evident between locations, whereas only a small but significant proportion of variation of assemblages between blocks within location was explained by reef surface area. No clear association with external predation pressure was evident in multivariate analyses of variation in assemblage structure. Juvenile abalone Haliotis rubra were not influenced by micro-habitat structure but were significantly less abundant at protected locations, the only species to exhibit such a response. This result follows a decline of emergent adult abalone in the marine reserve and raises the possibility of recruitment failure of abalone at some fully protected locations in the longer term.
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Cryptic species, i.e. species that are morphologically hard to distinguish, have been detected repeatedly in various taxa and ecosystems. In order to evaluate the importance of this finding, we have to know in how far cryptic species differ in various aspects of their biology. The amphipod Gammarus fossarum is a key invertebrate in freshwater streams and contains several cryptic species. We examined the population genetic structure, genetic diversity and demographic history of two of them (type A and type B) using microsatellite markers and asked whether they show significant differences. We present results of population genetic analyses based on a total of 37 populations from the headwaters of two major European drainages, Rhine and Rhone. We found that, in both species, genetic diversity was geographically structured among and within drainages. For type A in the Rhine and type B in the Rhone, we detected significant patterns of isolation by distance. The increase of genetic differentiation with geographical distance, however, was much higher in type A than in type B. This result indicates substantial interspecific differences in population history and/or the extent of current gene flow between populations. In the Rhine, type B does not show evidence of isolation by distance, and population differentiation is relatively low across hundreds of kilometres. The majority of these populations also show signatures of recent bottlenecks. These patterns are consistent with a recent expansion of type B into the Rhine drainage. In summary, our results suggest considerable and previously unrecognized interspecific differences in the genetic structure of these cryptic keystone species.
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Conspecific aggregation of waterfowl in winter is a common example of animal flocking behaviour, yet patterns of relatedness and temporal substructure in such social groups remain poorly understood even in common species. A previous study based on mark-recapture data showed that Tufted Ducks Aythya fuligula caught on the same day were re-caught together in subsequent winters more often than expected by chance, suggesting stable assortments of ‘socially familiar’ individuals between wintering periods. The genetic relationships within these social groups were not clear. Based on 191 individuals genotyped at 10 microsatellite markers, we investigated the temporal genetic structure and patterns of relatedness among wintering Tufted Ducks at Lake Sempach, Switzerland, in two consecutive winters. We found no evidence of genetic differentiation between temporal groups within or between winters. The average levels of relatedness in temporal groups were low and not higher than expected in random assortments of individuals. However, Mantel tests performed for each sex separately revealed significant negative correlations between the pairwise relatedness coefficients and the number of days between the capture dates of pairs of wintering Tufted Duck in males and females. This pattern suggests the presence of a small number of co-migrating same-sex sibling pairs in wintering flocks of Tufted Ducks. Our findings provide one of the first genetic analyses of a common duck species outside the breeding season and contribute to the understanding of social interactions in long-distance migratory birds.
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BACKGROUND: Research on comorbidity of psychiatric disorders identifies broad superordinate dimensions as underlying structure of psychopathology. While a syndrome-level approach informs diagnostic systems, a symptom-level approach is more likely to represent the dimensional components within existing diagnostic categories. It may capture general emotional, cognitive or physiological processes as underlying liabilities of different disorders and thus further develop dimensional-spectrum models of psychopathology. METHODS: Exploratory and confirmatory factor analyses were used to examine the structure of psychopathological symptoms assessed with the Brief Symptom Inventory in two outpatient samples (n=3171), including several correlated-factors and bifactor models. The preferred models were correlated with DSM-diagnoses. RESULTS: A model containing eight correlated factors for depressed mood, phobic fear, aggression, suicidal ideation, nervous tension, somatic symptoms, information processing deficits, and interpersonal insecurity, as well a bifactor model fit the data best. Distinct patterns of correlations with DSM-diagnoses identified a) distress-related disorders, i.e., mood disorders, PTSD, and personality disorders, which were associated with all correlated factors as well as the underlying general distress factor; b) anxiety disorders with more specific patterns of correlations; and c) disorders defined by behavioural or somatic dysfunctions, which were characterised by non-significant or negative correlations with most factors. CONCLUSIONS: This study identified emotional, somatic, cognitive, and interpersonal components of psychopathology as transdiagnostic psychopathological liabilities. These components can contribute to a more accurate description and taxonomy of psychopathology, may serve as phenotypic constructs for further aetiological research, and can inform the development of tailored general and specific interventions to treat mental disorders.
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Glucocorticoids (GC) are successfully applied in neonatology to improve lung maturation in preterm born babies. Animal studies show that GC can also impair lung development. In this investigation, we used a new approach based on digital image analysis. Microscopic images of lung parenchyma were skeletonised and the geometrical properties of the septal network characterised by analysing the 'skeletal' parameters. Inhibition of the process of alveolarisation after extensive administration of small doses of GC in newborn rats was confirmed by significant changes in the 'skeletal' parameters. The induced structural changes in the lung parenchyma were still present after 60 days in adult rats, clearly indicating a long lasting or even definitive impairment of lung development and maturation caused by GC. Conclusion: digital image analysis and skeletonisation proved to be a highly suited approach to assess structural changes in lung parenchyma.
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Chondrostoma nasus is a cyprinid fish with highly specialized, ecologically and geographically distinct, ontogenetic trophic niches. Nase population numbers across their Swiss range have shown massive declines and many localized extinctions. Here we integrate data from different genetic markers with phenotypic and demographic data to survey patterns of neutral and adaptive genetic diversity in all extant (and one extinct) Swiss nase populations, with the aim to delineate intraspecific conservation units (CUs) and to inform future population management strategies. We discovered two major genetically and geographically distinct population groupings. The first population grouping comprises nase inhabiting rivers flowing into Lake Constance; the second comprises nase populations from Rhine drainages below Lake Constance. Within these clusters there is generally limited genetic differentiation among populations. Genomic outlier scans based on 256–377 polymorphic AFLP loci revealed little evidence of local adaptation both within and among population clusters, with the exception of one candidate locus identified in scans involving the inbred Schanzengraben population. However, significant phenotypic differentiation in body shape between certain populations suggests a need for more intensive future studies of local adaptation. Our data strongly suggests that the two major population groups should be treated as distinct CUs, with any supplemental stocking and reintroductions sourced only from within the range of the CU concerned.
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Friedreich’s ataxia (FRDA) is caused by the transcriptional silencing of the frataxin (FXN) gene. FRDA patients have expansion of GAA repeats in intron 1 of the FXN gene in both alleles. A number of studies demonstrated that specific histone deacetylase inhibitors (HDACi) affect either histone modifications at the FXN gene or FXN expression in FRDA cells, indicating that the hyperexpanded GAA repeat may facilitate heterochromatin formation. However, the correlation between chromatin structure and transcription at the FXN gene is currently limited due to a lack of more detailed analysis. Therefore, I analyzed the effects of the hyperexpanded GAA repeats on transcription status and chromatin structure using lymphoid cell lines derived from FRDA patients. Using chromatin immunoprecipitation and quantitative PCR, I observed significant changes in the landscape of histone modifications in the vicinity of the GAA tract in FRDA cells relative to control cells. Similar epigenetic changes were observed in GFP reporter construct containing 560 GAA repeats. Further, I detected similar levels of FXN pre-mRNA at a region upstream of hyperexpanded GAA repeats in FRDA and control cells, indicating similar efficiency of transcription initiation in FRDA cells. I also showed that histone modifications associated with hyperexpanded GAA repeats are independent of transcription progression using the GFP reporter system. My data strongly support evidence that FXN deficiency in FRDA patients is consequence of defective transition from initiation to elongation of FXN transcription due to heterochromatin-like structures formed in the proximity of the hyperexpanded GAAs.
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Prostaglandin H synthase (PGHS) is a key enzyme in biosynthesis of prostaglandins, thromboxane, and prostacyclin. It has two activities, cyclooxygenase and peroxidase. "PGHS" means PGHS-1. A current hypothesis considers the cyclooxygenase reaction to be a free radical chain reaction, initiated by interaction of the synthase peroxidase with hydroperoxides leading to the production of a tyrosyl free radical. According to this hypothesis, tyrosyl residue(s) may play a key role in the cyclooxygenase reaction. Tetranitromethane (TNM) can relatively selectively nitrate tyrosines at pH 8.0. The effect of TNM on both cyclooxygenase activity and peroxidase activity has been examined: reaction of the synthase holoenzyme with TNM at pH 8.0 led to inactivation of both activities, with the cyclooxygenase activity being lost rapidly and completely, while the peroxidase activity was lost more slowly. Indomethacin, a non-steroidal anti-inflammatory agent, can protect the synthase from the inactivation of TNM. Amino acid analyses indicated that a loss of tyrosine and formation of nitrotyrosine residues occurred during reaction with TNM, and that TNM-reacted holoenzyme with $<$10% residual cyclooxygenase activity had about 2.0 nitrotyrosine/subunit.^ PGH synthase is known to be an endoplasmic reticulum membrane-associated protein. Antibodies directed at particular PGHS peptide segments and indirect immunofluorescence have been used to characterize the membrane topology of crucial portions of PGHS. PGHS was expressed in COS-1 cells transfected with the appropriate cDNA. Stably-transfected human endothelial cells were also used for the topology study. The cells were treated with streptolysin-O, which selectively permeabilizes the plasma membrane, or with saponin to achieve general membrane disruption, before incubation with the antipeptide antibodies. Bound antipeptide antibody was stained by FITC-labelled secondary antibody and visualized by fluorescence microscopy. With the antipeptide antibodies against residues 51-66, 156-170 or 377-390, there was a significant reticular and perinuclear pattern of staining in cells permeabilized with saponin but not in cells permeabilized with SLO alone. Antibodies directed against the endogenous C-terminal peptide or against residues 271-284 produced staining in cells permeabilized with saponin, and also in a lower, but significant fraction of cells permeabilized with SLO. Similar results were obtained when COS-1 cells expressing recombinant PGHS with a viral reporter peptide inserted at the C-terminus were stained with antibody against the reporter epitope.^ The PGHS C-terminal sequence is similar to that of the consensus KDEL ER retention signal. The potential function of the PGHS C-terminus segment in ER retention was examined by mutating this segment and analyzing the subcellular distribution of the mutants expressed in COS-1 cells. None of the mutants had an altered subcellular distribution, although some had greatly diminished the enzyme activities. (Abstract shortened by UMI.) ^
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PAX6 is a transcription activator that regulates eye development in animals ranging from Drosophila to human. The C-terminal region of PAX6 is proline/serine/threonine-rich (PST) and functions as a potent transactivation domain when attached to a heterologous DNA-binding domain of the yeast transcription factor, GAL4. The PST region comprises 152 amino acids encoded by four exons. The transactivation function of the PST region has not been defined and characterized in detail by in vitro mutagenesis. I dissected the PST domain in two independent systems, a heterologous system using a GAL4 DNA-binding site and the native system of PAX6. In both systems, the results show consistently that all four constituent exons of the PST domain are responsible for the transactivation function. The four exon fragments act cooperatively to stimulate transcription, although none of them can function individually as an independent transactivation domain. Combinations of two or more exon fragments can reconstitute substantial transactivation activity when fused to the DNA-binding domain of GAL4, but they surprisingly do not produce much activity in the context of native PAX6 even though the mutant PAX6 proteins are stable and their DNA-binding function remains unaffected. I conclude that the PAX6 protein contains an unusually large transactivation domain that is evolutionarily conserved to a high degree, and that its full transactivation activity relies on the cooperative action of the four exon fragments.^ Most PAX6 mutations detected in patients with aniridia result in truncations of the protein. Some of the truncation mutations occur in the PST region of PAX6, resulting in mutant proteins that retain their DNA-binding ability but have no significant transactivation activity. It is not clear whether such mutants are true loss-of-function or dominant-negative mutants. I show that these mutants are dominant-negative if they are coexpressed with wild-type PAX6 in cultured cells and that the dominant-negative effects result from enhanced DNA-binding ability of these mutants due to removal of the PST domain. These mutants are able to repress the wild-type PAX6 activity not only at target genes with paired domain binding sites but also at target genes with homeodomain binding sites.^ Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis, and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, I performed a functional analysis of two missense mutations in the paired domain: the R26G mutation reported in a case of Peters' anomaly, and the I87R mutation identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. I found that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. My data support the haploinsufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele. ^
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The evolution of pharmaceutical care is identified through a complete review of the literature published in the American Journal of Health-System Pharmacy, the sole comprehensive publication of institutional pharmacy practice. The evolution is categorized according to characteristics of structure (organizational structure, the role of the pharmacist), process (drug delivery systems, formulary management, acquiring drug products, methods to impact drug therapy decisions), and outcomes (cost of drug delivery, cost of drug acquisition and use, improved safety, improved health outcomes) recorded from the 1950s through the 1990s. While significant progress has been made in implementing basic drug distribution systems, levels of pharmacy involvement with direct patient care is still limited.^ A new practice framework suggests enhanced direct patient care involvement through increase in the efficiency and effectiveness of traditional pharmacy services. Recommendations advance internal and external organizational structure relationships that position pharmacists to fully use their unique skills and knowledge to impact drug therapy decisions and outcomes. Specific strategies facilitate expansion of the breadth and scope of each process component in order to expand the depth of integration of pharmacy and pharmaceutical care within the broad healthcare environment. Economic evaluation methods formally evaluate the impact of both operational and clinical interventions.^ Outcome measurements include specific recommendations and methods to increase efficiency of drug acquisition, emphasizing pharmacists' roles that impact physician prescribing decisions. Effectiveness measures include those that improve safety of drug distribution systems, decrease the potential of adverse drug therapy events, and demonstrate that pharmaceutical care can significantly contribute to improvement in overall health status.^ The implementation of the new framework is modeled on a case study at the M.D. Anderson Cancer Center. The implementation of several new drug distribution methods facilitated the redeployment of personnel from distributive functions to direct patient care activities with significant personnel and drug cost reduction. A cost-benefit analysis illustrates that framework process enhancements produced a benefit-to-cost ratio of 7.9. In addition, measures of effectiveness demonstrated significant levels of safety and enhanced drug therapy outcomes. ^
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Docetaxel (DCT) is an anticancer drug which acts by disrupting microtubule dynamics in the highly mitotic cancer cells. Thus, this drug has a potential to affect function and organization of tissues exhibiting high cellular turnover. We investigated, in the rabbit, the effects of a single human equivalent dose (6.26mg/kg, i.v.) of DCT on the olfactory mucosa (OM) through light and electron microscopy, morphometry, Ki-67 immunostaining, TUNEL assay and the buried food test for olfactory sensitivity. On post-exposure days (PED) 5 and 10, there was disarrangement of the normal cell layering in the olfactory epithelium (OE), apoptotic death of cells of the OE, Bowman's glands and axon bundles, and the presence (including on PED 3) of blood vessels in the bundle cores. A decrease in bundle diameters, olfactory cell densities and cilia numbers, which was most significant on PED 10 (49.3%, 63.4% and 50%, respectively), was also evident. Surprisingly by PED 15, the OM regained normal morphology. Furthermore, olfactory sensitivity decreased progressively until PED 10 when olfaction was markedly impaired, and with recovery from the impairment by PED 15. These observations show that DCT transiently alters the structure and function of the OM suggesting a high regenerative potential for this tissue.
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The phenomenon of premature chromosome condensation, resulting from fusion between mitotic and interphase cells, includes dissolution of the interphase nuclear framework, thus allowing a direct visualization of interphase chromosomes. Light microscope morphology of prematurely condensed chromosomes (PCC) from synchronized HeLa cells supports the model of an interphase "chromosome condensation cycle". PCC are increasingly attenuated as cells progress through G(,1). A maximum degree of decondensation is observed at active sites of DNA replication during S phase, and a condensed morphology is rapidly resumed following completion of replication of a chromosome segment.^ To permit ultrastructural and biochemical studies of PCC, a procedure was developed to induce premature chromosome condensation at high frequency. This was achieved by polyethylene glycol (PEG)-mediated fusion of a dense monolayer of mitotic and interphase cells induced by centrifugation onto lectin-coated culture dishes. Using this method, PCC induction frequencies of 60-90% are routinely obtained.^ Scanning electron microscope analysis of PCC spreads revealed that the extension of PCC during progression through G(,1) is accompanied by a transition of the basic 30 nm chromatin fiber from tightly packed looping fibers to extended longitudinal fibers. Sites of active DNA replication is S-PCC were indicated to be organized a single longitudinal fibers. Following replication of a chromosome segment, a rapid reorganization from the extended longitudinal fiber to packed looping fibers occurs. The postreplication maturation process appears to include the assembly of a chromosome core consisting of multiple longitudinal fibers.^ The role of histone H1 phosphorylation in PCC formation was investigated by acidurea polyacrylamide gel electrophoresis of total histone extracted from metaphase chromosomes and PCC following high frequency fusion. This investigation failed to demonstrate an extensive phosphorylation of H1 associated with PCC formation. However, significant dephosphorylation of superphosphorylated metaphase chromosome H1 was observed, indicating that interphase H1-phosphatase activity is dominant over metaphase H1 kinase activity. These observations provide evidence against models suggesting a role for H1 superphosphorylation in triggering mitotic condensation of chromosomes. ^
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Coagulase-negative staphylococci (CNS) are recognized as important pathogens and are particularly associated with foreign body infections. S. epidermidis accounts for approximately 75% of the infections caused by CNS. Three genes, sdrF, sdrG, and sdrH, were identified by screening a S. epidermidis genomic library with a probe encompassing the serine-aspartate dipeptide repeat-encoding region (region R) of clfA from S. aureus. SdrG has significant amino acid identity to ClfA, ClfB and other surface proteins of S. aureus. SdrG is also similar to a protein (Fbe) recently described by Nilsson, et al. (Infection and Immunity, 1998, 66:2666–73) from S. epidermidis. The N-terminal domain (A region) of SdrG was expressed as a his-tag fusion protein in E. coli. In an ELISA, this protein, rSdrG(50-597) was shown to bind specifically to fibrinogen (Fg). Western ligand blot analysis showed that SdrG binds the Bβ chain of Fg. To further characterize the rSdrG(50-597)-Fg interaction, truncates of the Fg Bβ chain were made and expressed as recombinant proteins in E. coli. SdrG was shown to bind the full-length Bβ chain (1462), as well as the N-terminal three-quarters (1-341), the N-terminal one-half (1-220) and the N-terminal one-quarter (1-95) Bβ chain constructs. rSdrG(50-597) failed to bind to the recombinant truncates that lacked the N-terminal 25 amino acid residues of this polypeptide suggesting that SdrG recognizes a site within this region of the Bβ chain. Inhibition ELISAs have shown that peptide mimetics, including β1–25, and β6–20, encompassing this 25 residue region can inhibit binding of rSdrG(50-597) to Fg coated wells. Using fluorescence polarization we were able to determine an equilibrium constant (KD) for the interaction of rSdrG(50-597) with the Fg Bβ chain peptide β1–25. The labeled peptide was shown to bind to rSdrG(50-597) with a KD of 0.14 ± 0.01μM. Because rSdrG(50-597) recognizes a site in the Fg Bβ chain close to the thrombin cleavage site, we investigated the possibility of the rSdrG(50-597) site either overlapping or lying close to this cleavage site. An ELISA showed that rSdrG(50-597) binding to thrombin-treated Fg was significantly reduced. In a clot inhibition assay rSdrG(50-597) was able to inhibit fibrin clot formation in a concentration dependent manner. Furthermore, rSdrG(50-597) was able to inhibit clot formation by preventing the release of fibrinopeptide B as determined by HPLC. To further define the interaction between rSdrG(50-597) and peptide β6–20, we utilized an alanine amino acid replacement strategy. The residues in β6–20 that appear to be important in rSdrG(50-597) binding to Fg, were confirmed by the rSdrG(273-597)-β6–20 co-crystal structure that was recently solved by our collaborators at University of Alabama-Birmingham. Additionally, rSdrG(50-597) was not able to bind to Fg from different animal species, rather it bound specifically to human Fg in an ELISA. This suggests that the sequence variation between Fg Bβ chains of different species, specifically with in the N-terminal 25 residues, affects the ability of rSdrG(50-597) binding to Fg, and this may explain why S. epidermidis is primarily a human pathogen. ^
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Regulatory change not seen since the Great Depression swept the U.S. banking industry beginning in the early 1980s, culminating with the Interstate Banking and Branching Efficiency Act of 1994. Significant consolidations have occurred in the banking industry. This paper considers the market-power versus the efficient-structure theories of the positive correlation between banking concentration and performance on a state-by-state basis. Temporal causality tests imply that bank concentration leads bank profitability, supporting the market-power, rather than the efficient-structure, theory of that positive correlation. Our finding suggests that bank regulators, by focusing on local banking markets, missed the initial stages of an important structural change at the state level.
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Uncertainty has been found to be a major component of the cancer experience and can dramatically affect psychosocial adaptation and outcomes of a patient's disease state (McCormick, 2002). Patients with a diagnosis of Carcinoma of Unknown Primary (CUP) may experience higher levels of uncertainty due to the unpredictability of current and future symptoms, limited treatment options and an undetermined life expectancy. To date, only one study has touched upon uncertainty and its' effects on those with CUP but no information exists concerning the effects of uncertainty regarding diagnosis and treatment on the distress level and psychosocial adjustment of this population (Parker & Lenzi, 2003). ^ Mishel's Uncertainty in Illness Theory (1984) proposes that uncertainty is preceded by three variables, one of which being Structure Providers. Structure Providers include credible authority, the degree of trust and confidence the patient has with their doctor, education and social support. It was the goal of this study to examine the relationship between uncertainty and Structure Providers to support the following hypotheses: (1) There will be a negative association between credible authority and uncertainty, (2) There will be a negative association between education level and uncertainty, and (3) There will be a negative association between social support and uncertainty. ^ This cross-sectional analysis utilized data from 219 patients following their initial consultation with their oncologist. Data included the Mishel Uncertainty in Illness Scale (MUIS) which was used to determine patients' uncertainty levels, the Medical Outcomes Study-Social Support Scale (MOSS-SSS) to assess patients, levels of social support, the Patient Satisfaction Questionnaire (PSQ-18) and the Cancer Diagnostic Interview Scale (CDIS) to measure credible authority and general demographic information to assess age, education, marital status and ethnicity. ^ In this study we found that uncertainty levels were generally higher in this sample as compared to other types of cancer populations. And while our results seemed to support most of our hypothesis, we were only able to show significant associations between two. The analyses indicated that credible authority measured by both the CDIS and the PSQ was a significant predictor of uncertainty as was social support measured by the MOSS-SS. Education has shown to have an inconsistent pattern of effect in relation to uncertainty and in the current study there was not enough data to significantly support our hypothesis. ^ The results of this study generally support Mishel's Theory of Uncertainty in Illness and highlight the importance of taking into consideration patients, psychosocial factors as well as employing proper communication practices between physicians and their patients.^