Competition vs. Profitability

Corporate cultural emphasis on long-term competitiveness as opposed to shorter-term profitability is evaluated in terms of effectiveness in achieving higher profit margins, real profitability, and survival in the long term. Competitive orientation continues to have adverse impact even with a lag of four decades. If supported by further, multivariate analyses, this finding suggests amendments to what has become standard strategic management thinking, perhaps in favor of earlier and more conventional microeconomic focus on profits

Intergenerational Service Learning Program Improves Aging Knowledge and Expectations and Reduces Ageism in Younger Adults

This article discusses a study which evaluated the effects of an intergenerational service-learning exergaming program for older adults on younger adults’ aging knowledge, expectations, and perceptions. Eighteen college students (ages 19-26 years) served as trainers for an 8-week exergaming physical activity program for older adults (12 contact hours). Questionnaires assessing aging knowledge, ageist attitudes and aging expectations were completed at Weeks 1, 8, and 25 (follow-up); program evaluations were completed at Weeks 8 and 25. Significant improvement from Week 1 to Week 25 was found for: Aging knowledge scores (

Geographic Clustering of Leishmaniasis in Northeastern Brazil1

Different forms of this disease are spreading rapidly in distinct geographic clusters in this region

Phosphoproteomics Screen Reveals Akt Isoform-Specific Signals Linking RNA Processing to Lung Cancer

The three Akt isoforms are functionally distinct. Here we show that their phosphoproteomes also differ, suggesting that their functional differences are due to differences in target specificity. One of the top cellular functions differentially regulated by Akt isoforms is RNA processing. IWS1, an RNA processing regulator, is phosphorylated by Akt3 and Akt1 at Ser720/Thr721. The latter is required for the recruitment of SETD2 to the RNA Pol II complex. SETD2 trimethylates histone H3 at K36 during transcription, creating a docking site for MRG15 and PTB. H3K36me3-bound MRG15 and PTB regulate FGFR-2 splicing, which controls tumor growth and invasiveness downstream of IWS1 phosphorylation. Twenty-one of the twenty-four non-small-cell-lung carcinomas we analyzed express IWS1. More importantly, the stoichiometry of IWS1 phosphorylation in these tumors correlates with the FGFR-2 splicing pattern and with Akt phosphorylation and Akt3 expression. These data identify an Akt isoform-dependent regulatory mechanism for RNA processing and demonstrate its role in lung cancer

A heterogeneous computing environment to solve the 768-bit RSA challenge

In December 2009 the 768-bit, 232-digit number RSA-768 was factored using the number field sieve. Overall, the computational challenge would take more than 1700 years on a single, standard core. In the article we present the heterogeneous computing approach, involving different compute clusters and Grid computing environments, used to solve this proble

RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association

The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting in RET transmembrane signaling. We present a hybrid structural model, derived from electron microscopy (EM) and low-angle X-ray scattering (SAXS) data, of the RET extracellular domain (RETECD), GDNF, and GFRα1 ternary complex, defining the basis for ligand recognition. RETECD envelopes the dimeric ligand complex through a composite binding site comprising four discrete contact sites. The GFRα1-mediated contacts are crucial, particularly close to the invariant RET calcium-binding site, whereas few direct contacts are made by GDNF, explaining how distinct ligand/coreceptor pairs are accommodated. The RETECD cysteine-rich domain (CRD) contacts both ligand components and makes homotypic membrane-proximal interactions occluding three different antibody epitopes. Coupling of these CRD-mediated interactions suggests models for ligand-induced RET activation and ligand-independent oncogenic deregulation

Crosstalk between Desmoglein 2 and Patched 1 accelerates chemical-induced skin tumorigenesis

Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 on Ptc1+/lacZ background enhanced epidermal proliferation and interfollicular activation of the Hh pathway. Furthermore, in response to DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous lessons earlier than the WT, Ptc1+/lacZ, and Inv-Dsg2 littermates. Additionally, DMBA/TPA induced BCC formation in all mice harboring the Ptc1+/lacZ gene and the presence of Dsg2 in Dsg2/Ptc1+/lacZ mice doubled the BCC tumor burden. Reporter analysis revealed activation of the Hh pathway in the BCC tumors. However, in the SCCs we observed Hh activity only in the underlying dermis of the tumors. Furthermore, Dsg2/Ptc1+/lacZ mice demonstrated enhanced MEK/Erk1/2 activation within the tumors and expression of Shh in the dermis. In summary, our results demonstrate that Dsg2 modulates Hh signaling, and this synergy may accelerate skin tumor development by different mechanisms

Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study

PurposeTo evaluate the safety and efficacy of radiofrequency (RF) ablation of the basivertebral nerve (BVN) for the treatment of chronic low back pain (CLBP) in a Food and Drug Administration approved Investigational Device Exemption trial. The BVN has been shown to innervate endplate nociceptors which are thought to be a source of CLBP.MethodsA total of 225 patients diagnosed with CLBP were randomized to either a sham (78 patients) or treatment (147 patients) intervention. The mean age within the study was 47 years (range 25–69) and the mean baseline ODI was 42. All patients had Type I or Type II Modic changes of the treated vertebral bodies. Patients were evaluated preoperatively, and at 2 weeks, 6 weeks and 3, 6 and 12 months postoperatively. The primary endpoint was the comparative change in ODI from baseline to 3 months.ResultsAt 3 months, the average ODI in the treatment arm decreased 20.5 points, as compared to a 15.2 point decrease in the sham arm (p = 0.019, per-protocol population). A responder analysis based on ODI decrease ≥ 10 points showed that 75.6% of patients in the treatment arm as compared to 55.3% in the sham control arm exhibited a clinically meaningful improvement at 3 months.ConclusionPatients treated with RF ablation of the BVN for CLBP exhibited significantly greater improvement in ODI at 3 months and a higher responder rate than sham treated controls. BVN ablation represents a potential minimally invasive treatment for the relief of chronic low back pain.Graphical abstract These slides can be retrieved under Electronic Supplementary Material. Open image in new windo

Process evaluation of appreciative inquiry to translate pain management evidence into pediatric nursing practice

Background Appreciative inquiry (AI) is an innovative knowledge translation (KT) intervention that is compatible with the Promoting Action on Research in Health Services (PARiHS) framework. This study explored the innovative use of AI as a theoretically based KT intervention applied to a clinical issue in an inpatient pediatric care setting. The implementation of AI was explored in terms of its acceptability, fidelity, and feasibility as a KT intervention in pain management. Methods A mixed-methods case study design was used. The case was a surgical unit in a pediatric academic-affiliated hospital. The sample consisted of nurses in leadership positions and staff nurses interested in the study. Data on the AI intervention implementation were collected by digitally recording the AI sessions, maintaining logs, and conducting individual semistructured interviews. Data were analysed using qualitative and quantitative content analyses and descriptive statistics. Findings were triangulated in the discussion. Results Three nurse leaders and nine staff members participated in the study. Participants were generally satisfied with the intervention, which consisted of four 3-hour, interactive AI sessions delivered over two weeks to promote change based on positive examples of pain management in the unit and staff implementation of an action plan. The AI sessions were delivered with high fidelity and 11 of 12 participants attended all four sessions, where they developed an action plan to enhance evidence-based pain assessment documentation. Participants labeled AI a 'refreshing approach to change' because it was positive, democratic, and built on existing practices. Several barriers affected their implementation of the action plan, including a context of change overload, logistics, busyness, and a lack of organised follow-up. Conclusions Results of this case study supported the acceptability, fidelity, and feasibility of AI as a KT intervention in pain management. The AI intervention requires minor refinements (e.g., incorporating continued follow-up meetings) to enhance its clinical utility and sustainability. The implementation process and effectiveness of the modified AI intervention require evaluation in a larger multisite study