Champions, converts, doubters, and defectors: the impact of shifting perceptions on momentum for change

Maintaining momentum is a key influence on the ultimate success of large-scale change. In this paper, we develop theory to explain how stable vs. shifting change-supportive perceptions over time differentially influence the perceived momentum associated with goal-directed change (i.e., change-based momentum). We use cross-level polynomial regression and data obtained early and one year later within an organization implementing a lean manufacturing transformation to model changes in individual perceptions. Results suggest that momentum perceptions are higher for “Champions” (stable and high perceptions over time) as compared to “Converts” (increasing perceptions over time), but momentum perceptions are lower for “Defectors” (decreasing perceptions over time) as compared to “Doubters” (stable and low perceptions over time). We find that even if participants converge upon change-supportive perceptions later in the change process, early divergent perceptions influence subsequent momentum for the change. These findings highlight the important role of temporal shifts in perceptions for organizational change processes

Fanconi anemia genes are highly expressed in primitive CD34(+ )hematopoietic cells

BACKGROUND: Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. METHODS: Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. RESULTS: We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34(- )stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. CONCLUSIONS: These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34(+ )cells correlates with a role at the CD34(+ )differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism

The relationship between hip abductor muscle strength and iliotibial band tightness in individuals with low back pain

<p>Abstract</p> <p>Background</p> <p>Shortening of the iliotibial band (ITB) has been considered to be associated with low back pain (LBP). It is theorized that ITB tightness in individuals with LBP is a compensatory mechanism following hip abductor muscle weakness. However, no study has clinically examined this theory. The purpose of this study was to investigate the muscle imbalance of hip abductor muscle weakness and ITB tightness in subjects with LBP.</p> <p>Methods</p> <p>A total of 300 subjects with and without LBP between the ages of 20 and 60 participated in this cross-sectional study. Subjects were categorized in three groups: LBP with ITB tightness (n = 100), LBP without ITB tightness (n = 100) and no LBP (n = 100). Hip abductor muscle strength was measured in all subjects.</p> <p>Results</p> <p>Analysis of Covariance (ANCOVA) with the body mass index (BMI) as the covariate revealed significant difference in hip abductor strength between three groups (P < 0.001). Post hoc analysis showed no significant difference in hip abductor muscle strength between the LBP subjects with and without ITB tightness (P = 0.59). However, subjects with no LBP had significantly stronger hip abductor muscle strength compared to subjects with LBP with ITB tightness (P < 0.001) and those with LBP without ITB tightness (P < 0.001).</p> <p>Conclusion</p> <p>The relationship between ITB tightness and hip abductor weakness in patients with LBP is not supported as assumed in theory. More clinical studies are needed to assess the theory of muscle imbalance of hip abductor weakness and ITB tightness in LBP.</p

Monophyly of clade III nematodes is not supported by phylogenetic analysis of complete mitochondrial genome sequences

<p>Abstract</p> <p>Background</p> <p>The orders Ascaridida, Oxyurida, and Spirurida represent major components of zooparasitic nematode diversity, including many species of veterinary and medical importance. Phylum-wide nematode phylogenetic hypotheses have mainly been based on nuclear rDNA sequences, but more recently complete mitochondrial (mtDNA) gene sequences have provided another source of molecular information to evaluate relationships. Although there is much agreement between nuclear rDNA and mtDNA phylogenies, relationships among certain major clades are different. In this study we report that mtDNA sequences do not support the monophyly of Ascaridida, Oxyurida and Spirurida (clade III) in contrast to results for nuclear rDNA. Results from mtDNA genomes show promise as an additional independently evolving genome for developing phylogenetic hypotheses for nematodes, although substantially increased taxon sampling is needed for enhanced comparative value with nuclear rDNA. Ultimately, topological incongruence (and congruence) between nuclear rDNA and mtDNA phylogenetic hypotheses will need to be tested relative to additional independent loci that provide appropriate levels of resolution.</p> <p>Results</p> <p>For this comparative phylogenetic study, we determined the complete mitochondrial genome sequences of three nematode species, <it>Cucullanus robustus </it>(13,972 bp) representing Ascaridida, <it>Wellcomia </it><it>siamensis </it>(14,128 bp) representing Oxyurida, and <it>Heliconema longissimum </it>(13,610 bp) representing Spirurida. These new sequences were used along with 33 published nematode mitochondrial genomes to investigate phylogenetic relationships among chromadorean orders. Phylogenetic analyses of both nucleotide and amino acid sequence datasets support the hypothesis that Ascaridida is nested within Rhabditida. The position of Oxyurida within Chromadorea varies among analyses; in most analyses this order is sister to the Ascaridida plus Rhabditida clade, with representative Spirurida forming a distinct clade, however, in one case Oxyurida is sister to Spirurida. Ascaridida, Oxyurida, and Spirurida (the sampled clade III taxa) do not form a monophyletic group based on complete mitochondrial DNA sequences. Tree topology tests revealed that constraining clade III taxa to be monophyletic, given the mtDNA datasets analyzed, was a significantly worse result.</p> <p>Conclusion</p> <p>The phylogenetic hypotheses from comparative analysis of the complete mitochondrial genome data (analysis of nucleotide and amino acid datasets, and nucleotide data excluding 3^rdpositions) indicates that nematodes representing Ascaridida, Oxyurida and Spirurida do not share an exclusive most recent common ancestor, in contrast to published results based on nuclear ribosomal DNA. Overall, mtDNA genome data provides reliable support for nematode relationships that often corroborates findings based on nuclear rDNA. It is anticipated that additional taxonomic sampling will provide a wealth of information on mitochondrial genome evolution and sequence data for developing phylogenetic hypotheses for the phylum Nematoda.</p

Low back pain status in elite and semi-elite Australian football codes: a cross-sectional survey of football (soccer), Australian rules, rugby league, rugby union and non-athletic controls

<p>Abstract</p> <p>Background</p> <p>Our understanding of the effects of football code participation on low back pain (LBP) is limited. It is unclear whether LBP is more prevalent in athletic populations or differs between levels of competition. Thus it was the aim of this study to document and compare the prevalence, intensity, quality and frequency of LBP between elite and semi-elite male Australian football code participants and a non-athletic group.</p> <p>Methods</p> <p>A cross-sectional survey of elite and semi-elite male Australian football code participants and a non-athletic group was performed. Participants completed a self-reported questionnaire incorporating the Quadruple Visual Analogue Scale (QVAS) and McGill Pain Questionnaire (short form) (MPQ-SF), along with additional questions adapted from an Australian epidemiological study. Respondents were 271 elite players (mean age 23.3, range 17–39), 360 semi-elite players (mean age 23.8, range 16–46) and 148 non-athletic controls (mean age 23.9, range 18–39).</p> <p>Results</p> <p>Groups were matched for age (p = 0.42) and experienced the same age of first onset LBP (p = 0.40). A significant linear increase in LBP from the non-athletic group, to the semi-elite and elite groups for the QVAS and the MPQ-SF was evident (p < 0.001). Elite subjects were more likely to experience more frequent (daily or weekly OR 1.77, 95% CI 1.29–2.42) and severe LBP (discomforting and greater OR 1.75, 95% CI 1.29–2.38).</p> <p>Conclusion</p> <p>Foolers in Australia have significantly more severe and frequent LBP than a non-athletic group and this escalates with level of competition.</p

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Lovastatin Modulates Glycogen Synthase Kinase-3β Pathway and Inhibits Mossy Fiber Sprouting after Pilocarpine-Induced Status Epilepticus

This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis

Integrated genomics of susceptibility to alkylator-induced leukemia in mice

<p>Abstract</p> <p>Background</p> <p>Therapy-related acute myeloid leukemia (t-AML) is a secondary, generally incurable, malignancy attributable to chemotherapy exposure. Although there is a genetic component to t-AML susceptibility in mice, the relevant loci and the mechanism(s) by which they contribute to t-AML are largely unknown. An improved understanding of susceptibility factors and the biological processes in which they act may lead to the development of t-AML prevention strategies.</p> <p>Results</p> <p>In this work we applied an integrated genomics strategy in inbred strains of mice to find novel factors that might contribute to susceptibility. We found that the pre-exposure transcriptional state of hematopoietic stem/progenitor cells predicts susceptibility status. More than 900 genes were differentially expressed between susceptible and resistant strains and were highly enriched in the apoptotic program, but it remained unclear which genes, if any, contribute directly to t-AML susceptibility. To address this issue, we integrated gene expression data with genetic information, including single nucleotide polymorphisms (SNPs) and DNA copy number variants (CNVs), to identify genetic networks underlying t-AML susceptibility. The 30 t-AML susceptibility networks we found are robust: they were validated in independent, previously published expression data, and different analytical methods converge on them. Further, the networks are enriched in genes involved in cell cycle and DNA repair (pathways not discovered in traditional differential expression analysis), suggesting that these processes contribute to t-AML susceptibility. Within these networks, the putative regulators (e.g., <it>Parp2</it>, <it>Casp9</it>, <it>Polr1b</it>) are the most likely to have a non-redundant role in the pathogenesis of t-AML. While identifying these networks, we found that current CNVR and SNP-based haplotype maps in mice represented distinct sources of genetic variation contributing to expression variation, implying that mapping studies utilizing either source alone will have reduced sensitivity.</p> <p>Conclusion</p> <p>The identification and prioritization of genes and networks not previously implicated in t-AML generates novel hypotheses on the biology and treatment of this disease that will be the focus of future research.</p

Conflict transformation and history teaching: social psychological theory and its contributions

The aim of this introductory chapter is to render intelligible how history teaching can be enriched with knowledge of social psychological theories that deal with the issue of conflict transformation and partcularly the notions of prejudice reduction and reconciliation. A major aim of history teaching is to engage students with historical texts, establish historical significance, identify continuity and change, analyse cause and consequence, take historical perspectives and understand the ethical dimensions of historical interpretations. Such teaching, enriched with social psychological theory, will enlarge the notion of historical literacy into a study of historical culture and historical consciousness in the classroom so that students become reflective of the role of collective memory and history teaching in processes of conflict transformation and understand the ways in which various forms of historical consciousness relate the past, present and future. This is what the editors of this volume call an interdisciplinary paradigm of transformative history teachin