18 research outputs found
Factor Analytic Study to Evaluate the Structure of the Survey of Perceived Organizational Support
The original 36-item survey of perceived organizational support (SPOS) was evaluated to determine the underlying structure of the instrument. The survey items were subjected to a principal axis factor analysis. Reliability analyses for shorter versions of the SPOS were also conducted as a means to compare the internal consistency across forms (36-items, 16-items, 8-items, and 3-items). Finally, to evaluate the validity of the total scores for the different versions of SPOS, total scores from the three versions were regressed on three measures commonly included in studies that also use the SPOS: affective commitment, organizational participation, and organizational communication. Results indicate that the 36-item survey of perceived organizational support is unidimensional. The three versions that contain a reduced number of POS items are also unidimensional. All four versions of the SPOS are comparable in terms of internal consistency reliability. Likewise, all four versions performed equally in terms of thSchool of Teaching and Curriculum Leadershi
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ErbB4 promotes malignant peripheral nerve sheath tumor pathogenesis via Ras-independent mechanisms
Background
We have found that erbB receptor tyrosine kinases drive Ras hyperactivation and growth in NF1-null malignant peripheral nerve sheath tumors (MPNSTs). However, MPNSTs variably express multiple erbB receptors with distinct functional characteristics and it is not clear which of these receptors drive MPNST pathogenesis. Here, we test the hypothesis that altered erbB4 expression promotes MPNST pathogenesis by uniquely activating key cytoplasmic signaling cascades.
Methods
ErbB4 expression was assessed using immunohistochemistry, immunocytochemistry, immunoblotting and real-time PCR. To define erbB4 functions, we generated mice that develop MPNSTs with floxed Erbb4 alleles (P0-GGFβ3;Trp53+/−;Erbb4flox/flox mice) and ablated Erbb4 in these tumors. MPNST cell proliferation and survival was assessed using 3H-thymidine incorporation, MTT assays, Real-Time Glo and cell count assays. Control and Erbb4-null MPNST cells were orthotopically xenografted in immunodeficient mice and the growth, proliferation (Ki67 labeling), apoptosis (TUNEL labeling) and angiogenesis of these grafts was analyzed. Antibody arrays querying cytoplasmic kinases were used to identify erbB4-responsive kinases. Pharmacologic or genetic inhibition was used to identify erbB4-responsive kinases that drive proliferation.
Results
Aberrant erbB4 expression was evident in 25/30 surgically resected human MPNSTs and in MPNSTs from genetically engineered mouse models (P0-GGFβ3 and P0-GGFβ3;Trp53+/− mice); multiple erbB4 splice variants that differ in their ability to activate PI3 kinase and nuclear signaling were present in MPNST-derived cell lines. Erbb4-null MPNST cells demonstrated decreased proliferation and survival and altered morphology relative to non-ablated controls. Orthotopic allografts of Erbb4-null cells were significantly smaller than controls, with reduced proliferation, survival and vascularization. ERBB4 knockdown in human MPNST cells similarly inhibited DNA synthesis and viability. Although we have previously shown that broad-spectrum erbB inhibitors inhibit Ras activation, Erbb4 ablation did not affect Ras activation, suggesting that erbB4 drives neoplasia via non-Ras dependent pathways. An analysis of 43 candidate kinases identified multiple NRG1β-responsive and erbB4-dependent signaling cascades including the PI3K, WNK1, STAT3, STAT5 and phospholipase-Cγ pathways. Although WNK1 inhibition did not alter proliferation, inhibition of STAT3, STAT5 and phospholipase-Cγ markedly reduced proliferation.
Conclusions
ErbB4 promotes MPNST growth by activating key non-Ras dependent signaling cascades including the STAT3, STAT5 and phospholipase-Cγ pathways. ErbB4 and its effector pathways are thus potentially useful therapeutic targets in MPNSTs
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants
To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs
The survey of perceived organisational support: Which measure should we use?
The psychometric properties of the original 36-item Survey of Perceived Organisational Support (SPOS) was examined along with a variety of shorter versions currently in use (16 items, eight items and three items). Factor analysis of the original SPOS measure is supportive of the original finding that the SPOS is unidimensional. Correlations among factor scores and SPOS scale scores suggest that either the eight-item or 16-item version would be just as effective as the 36-item version but even more efficient. Convergent validity results also indicate similar proportions of variance in versions of SPOS scores accounted for by selected organisational variables
Psychometric Properties of the Serbian Version of the Maslach Burnout Inventory-Human Services Survey: A Validation Study among Anesthesiologists from Belgrade Teaching Hospitals
We report findings from a validation study of the translated and culturally adapted Serbian version of Maslach Burnout Inventory-Human Services Survey (MBI-HSS), for a sample of anesthesiologists working in the tertiary healthcare. The results showed the sufficient overall reliability (Cronbach’s α = 0.72) of the scores (items 1–22). The results of Bartlett’s test of sphericity (χ2 = 1983.75, df = 231, p<0.001) and Kaiser-Meyer-Olkin measure of sampling adequacy (0.866) provided solid justification for factor analysis. In order to increase sensitivity of this questionnaire, we performed unfitted factor analysis model (eigenvalue greater than 1) which enabled us to extract the most suitable factor structure for our study instrument. The exploratory factor analysis model revealed five factors with eigenvalues greater than 1.0, explaining 62.0% of cumulative variance. Velicer’s MAP test has supported five-factor model with the smallest average squared correlation of 0,184. This study indicated that Serbian version of the MBI-HSS is a reliable and valid instrument to measure burnout among a population of anesthesiologists. Results confirmed strong psychometric characteristics of the study instrument, with recommendations for interpretation of two new factors that may be unique to the Serbian version of the MBI-HSS