Chaos and Elliptical Galaxies

Recent results on chaos in triaxial galaxy models are reviewed. Central mass concentrations like those observed in early-type galaxies -- either stellar cusps, or massive black holes -- render most of the box orbits in a triaxial potential stochastic. Typical Liapunov times are 3-5 crossing times, and ensembles of stochastic orbits undergo mixing on time scales that are roughly an order of magnitude longer. The replacement of the regular orbits by stochastic orbits reduces the freedom to construct self-consistent equilibria, and strong triaxiality can be ruled out for galaxies with sufficiently high central mass concentrations.Comment: uuencoded gziped PostScript, 12 pages including figure

Gene expression signatures associated with the in vitro resistance to two tyrosine kinase inhibitors, nilotinib and imatinib

The use of selective inhibitors targeting Bcr-Abl kinase is now established as a standard protocol in the treatment of chronic myelogenous leukemia; however, the acquisition of drug resistance is a major obstacle limiting the treatment efficacy. To elucidate the molecular mechanism of drug resistance, we established K562 cell line models resistant to nilotinib and imatinib. Microarray-based transcriptome profiling of resistant cells revealed that nilotinib- and imatinib-resistant cells showed the upregulation of kinase-encoding genes (AURKC, FYN, SYK, BTK and YES1). Among them, the upregulation of AURKC and FYN was observed both in nilotinib- and imatinib-resistant cells irrespective of exposure doses, while SYK, BTK and YES1 showed dose-dependent upregulation of expression. Upregulation of EGF and JAG1 oncogenes as well as genes encoding ATP-dependent drug efflux pump proteins such as ABCB1 was also observed in the resistant cells, which may confer alternative survival benefits. Functional gene set analysis revealed that molecular categories of ‘ATPase activity', ‘cell adhesion' or ‘tyrosine kinase activity' were commonly activated in the resistant clones. Taken together, the transcriptome analysis of tyrosine kinase inhibitors (TKI)-resistant clones provides the insights into the mechanism of drug resistance, which can facilitate the development of an effective screening method as well as therapeutic intervention to deal with TKI resistance

BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

BACKGROUND: The reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+) the derivative 9+ encodes either the p40((ABL/BCR) )fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96((ABL/BCR) )fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. METHODS: We investigated the effects of BCR and ABL/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. RESULTS: Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. CONCLUSION: Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL/BCR fusion proteins in comparison to their physiological counterpart BCR

Breast cancer risk factor knowledge among nurses in teaching hospitals of Karachi, Pakistan: a cross-sectional study

BACKGROUND: Breast cancer is the most common cancer among women in both the developed and the developing world. The incidence of breast cancer in Karachi, Pakistan is 69.1 per 100,000 with breast cancer presentation in stages III and IV being common (≥ 50%). The most pragmatic solution to early detection lies in breast cancer education of women. Nurses constitute a special group having characteristics most suited for disseminating breast cancer information to the women. We assessed the level of knowledge of breast cancer risk factors among registered female nurses in teaching hospitals of Karachi. We also identified whether selected factors among nurses were associated with their knowledge of breast cancer risk factors, so that relevant measures to improve knowledge of nurses could be implemented. METHODS: A cross-sectional survey was conducted in seven teaching hospitals of Karachi using stratified random sampling with proportional allocation. A total of 609 registered female nurses were interviewed using a structured questionnaire adapted from the Stager's Comprehensive Breast Cancer Knowledge Test. Knowledge of breast cancer risk factors was categorized into good, fair and poor categories. Ordinal regression was used to identify factors associated with risk knowledge among nurses. RESULTS: Thirty five percent of nurses had good knowledge of risk factors. Graduates from private nursing schools (aOR = 4.23, 95% CI: 2.93, 6.10), nurses who had cared for breast cancer patients (aOR = 1.41, 95% CI: 1.00, 1.99), those having received a breast examination themselves (aOR = 1.56, 95% CI: 1.08, 2.26) or those who ever examined a patient's breast (aOR = 1.87, 95% CI: 1.34, 2.61) were more likely to have good knowledge. CONCLUSION: A relatively small proportion of the nursing population had good level of knowledge of the breast cancer risk factors. This knowledge is associated with nursing school status, professional breast cancer exposure and self history of clinical breast examination. Since only about one-third of the nurses had good knowledge about risk factors, there is a need to introduce breast cancer education in nursing schools particularly in the public sector. Continuing nursing education at the workplace can be of additional benefit

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population

Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery

<p>Abstract</p> <p>Background</p> <p>Cutpoints (CPs) for mild, moderate and severe pain are established and used primarily in cancer pain. In this study, we wanted to determine the optimal CPs for mild, moderate, and severe pain in joint replacement surgery candidates with osteoarthritis (OA) of the hip or knee, and to validate the different CPs.</p> <p>Methods</p> <p>Patients (n = 353) completed the Brief Pain Inventory (BPI), the WOMAC Arthritis Index, and the SF-36 health status measure. Optimal CPs for categorizing average pain with three severity levels were derived using multivariate analysis of variance, using different CP sets for average pain as the independent variable and seven interference items from the BPI as the dependent variable. To validate the CPs, we assessed if patients in the three pain severity groups differed in pain as assessed with WOMAC and SF-36, and if BPI average pain with the optimal CPs resulted in higher correlation with pain dimensions of the WOMAC and SF-36 than other CPs.</p> <p>Results</p> <p>The optimal CPs on the 0–10 point BPI scale were CP (4,6) among hip patients and CP (4,7) among knee patients. The resulting pain severity groups differed in pain, as assessed with other scales than those used to derive the CPs. The optimal CPs had the highest association of average pain with WOMAC pain scores.</p> <p>Conclusion</p> <p>CPs for pain severity differed somewhat for patients with OA of the hip and knee. The association of BPI average pain scores categorized according to the optimal CPs with WOMAC pain scores supports the validity of the derived optimal CPs.</p

Use Of Medical Tourism For Hip And Knee Surgery In Osteoarthritis: A Qualitative Examination Of Distinctive Attitudinal Characteristics Among Canadian Patients

Background Medical tourism is the term that describes patients’ international travel with the intention of seeking medical treatment. Some medical tourists go abroad for orthopaedic surgeries, including hip and knee resurfacing and replacement. In this article we examine the findings of interviews with Canadian medical tourists who went abroad for such surgeries to determine what is distinctive about their attitudes when compared to existing qualitative research findings about patients’ decision-making in and experiences of these same procedures in their home countries. Methods Fourteen Canadian medical tourists participated in semi-structured phone interviews, all of whom had gone abroad for hip or knee surgery to treat osteoarthritis. Transcripts were coded and thematically analysed, which involved comparing emerging findings to those in the existing qualitative literature on hip and knee surgery. Results Three distinctive attitudinal characteristics among participants were identified when interview themes were compared to findings in the existing qualitative research on hip and knee surgery in osteoarthritis. These attitudinal characteristics were that the medical tourists we spoke with were: (1) comfortable health-related decision-makers; (2) unwavering in their views about procedure necessity and urgency; and (3) firm in their desires to maintain active lives. Conclusions Compared to other patients reported on in the existing qualitative hip and knee surgery literature, medical tourists are less likely to question their need for surgery and are particularly active in their pursuit of surgical intervention. They are also comfortable with taking control of health-related decisions. Future research is needed to identify motivators behind patients’ pursuit of care abroad, determine if the attitudinal characteristics identified here hold true for other patient groups, and ascertain the impact of these attitudinal characteristics on surgical outcomes. Arthritis care providers can use the attitudinal characteristics identified here to better advise osteoarthritis patients who are considering seeking care abroad

Connectivity precedes function in the development of the visual word form area

What determines the cortical location at which a given functionally specific region will arise in development? We tested the hypothesis that functionally specific regions develop in their characteristic locations because of pre-existing differences in the extrinsic connectivity of that region to the rest of the brain. We exploited the visual word form area (VWFA) as a test case, scanning children with diffusion and functional imaging at age 5, before they learned to read, and at age 8, after they learned to read. We found the VWFA developed functionally in this interval and that its location in a particular child at age 8 could be predicted from that child's connectivity fingerprints (but not functional responses) at age 5. These results suggest that early connectivity instructs the functional development of the VWFA, possibly reflecting a general mechanism of cortical development.National Institutes of Health (U.S.) (Grant F32HD079169)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant F32HD079169)National Institutes of Health (U.S.) (Grant R01HD067312)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant R01HD067312

Overexpression of S100A4 in human cancer cell lines resistant to methotrexate

Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance. Methods: The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for β-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway. Results: S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. β-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells. Conclusions: S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistanc