1,340 research outputs found
Daring to DREAM: Results from a mentoring programme for at-risk youth
Recent research and empirical investigations of mentoring programmes have focused on how mentors can help at-risk youth to develop trusting relationships through consistent frequency of contact and emotional closeness. Many mentoring programmes are also geared toward enhancing students’ academic potential. This quantitative study examined whether participation in DREAM, a Northeastern United States, activity-based mentoring programme, was positively associated with children’s physical self-efficacy; global self-esteem; academic self-concept and educational expectations and their interest in travel experiences. Self-report data were collected from participating mentors and mentees. The results indicated that adjustment outcomes for boys and children over ten evidenced the strongest pattern of links with mentors’ reports
My Road Ahead study protocol: a randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer
BACKGROUND There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone. METHODS/DESIGN This study utilises a RCT design with three groups receiving: 1) the 6-module My Road Ahead intervention alone; 2) the My Road Ahead intervention plus a moderated online forum; and 3) the moderated online forum alone. It is expected that 150 men with localised prostate cancer will be recruited into the RCT. Online measures will assess men's psychological distress as well as sexual and relationship adjustment at baseline, post-intervention, 3 month follow-up and 6 month follow-up. The study is being conducted in Australia and participants will be recruited from April 2012 to Feb 2014. The primary aim of this study is to evaluate the efficacy of My Road Ahead in reducing psychological distress. DISCUSSION To our knowledge, My Road Ahead is the first self-directed online psychological intervention developed for men who have been treated for localised prostate cancer. The RCT will assess the efficacy of this intervention in improving psychological well-being, sexual satisfaction, relationship satisfaction and overall quality of life. If successful, this intervention could provide much needed support to men receiving treatment for localised prostate cancer in a highly accessible manner. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry Identifier: ACTRN12611000278932.The authors would like to acknowledge the funding partners involved in this study; the Prostate Cancer Foundation of Australia (PCFA), beyondblue: the
National Depression and Anxiety Initiative with funding support from Movember Foundation
Interstellar and Circumstellar Optical & Ultraviolet Lines Towards SN1998S
We have observed SN1998S which exploded in NGC3877, with the UES at the WHT
and with the E230M echelle of STIS aboard HST. Both data sets were obtained at
two seperate epochs. From our own Galaxy we detect interstellar absorption
lines of CaII, FeII, MgI, and probably MnII from the edge of the HVC Complex M.
We derive gas-phase abundances which are very similar to warm disk clouds in
the local ISM, which we believe argues against the HVC material having an
extragalactic origin. At the velocity of NGC3877 we detect interstellar MgI,
MgII, MnII, CaII, & NaI. Surprisingly, one component is seen to increase by a
factor of ~1 dex in N(NaI) and N(MgI) between the two epochs over which the
data were taken. Unusually, our data also show narrow Balmer, HeI, and
metastable FeII P-Cygni profiles, with a narrow absorption component
superimposed on the bottom of the profile's absorption trough. Both the broad
and narrow components of the optical lines are seen to increase substantially
in strength between the two epochs. Most of the low-ionization absorption can
be understood in terms of gas co-rotating with the disk of NGC 3877, providing
the SN is at the back of an HI disk with a similar thickness to that of our own
Galaxy. However, the variable absorption components, and the classic P-Cygni
emission profiles, most likely arise in slow-moving circumstellar outflows
originating from the red supergiant progenitor of SN1998S. [Abridged.]Comment: Accepted by ApJ, 26 pages including 9 figure
Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. METHODS: MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. RESULTS: Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3). CONCLUSION: Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer
Thrombin Induces Macrophage Migration Inhibitory Factor Release and Upregulation in Urothelium: A Possible Contribution to Bladder Inflammation
Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine expressed by urothelial cells that mediates bladder inflammation. We investigated the effect of stimulation with thrombin, a Protease Activated Receptor-1 (PAR1) agonist, on MIF release and MIF mRNA upregulation in urothelial cells.MIF and PAR1 expression was examined in normal human immortalized urothelial cells (UROtsa) using real-time RT-PCR, Western blotting and dual immunostaining. MIF and PAR1 immunostaining was also examined in rat urothelium. The effect of thrombin stimulation (100 nM) on urothelial MIF release was examined in UROtsa cells (in vitro) and in rats (in vivo). UROtsa cells were stimulated with thrombin, culture media were collected at different time points and MIF amounts were determined by ELISA. Pentobarbital anesthetized rats received intravesical saline (control), thrombin, or thrombin +2% lidocaine (to block nerve activity) for 1 hr, intraluminal fluid was collected and MIF amounts determined by ELISA. Bladder or UROtsa MIF mRNA was measured using real time RT-PCR.UROtsa cells constitutively express MIF and PAR1 and immunostaining for both was observed in these cells and in the basal and intermediate layers of rat urothelium. Thrombin stimulation of urothelial cells resulted in a concentration- and time-dependent increase in MIF release both in vitro (UROtsa; 2.8-fold increase at 1 hr) and in vivo (rat; 4.5-fold) while heat-inactivated thrombin had no effect. In rats, thrombin-induced MIF release was reduced but not abolished by intravesical lidocaine treatment. Thrombin also upregulated MIF mRNA in UROtsa cells (3.3-fold increase) and in the rat bladder (2-fold increase) where the effect was reduced (1.4-fold) by lidocaine treatment.Urothelial cells express both MIF and PAR1. Activation of urothelial PAR1 receptors, either by locally generated thrombin or proteases present in the urine, may mediate bladder inflammation by inducing urothelial MIF release and upregulating urothelial MIF expression
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A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas
Background
Relapsed and refractory sarcomas continue to have poor survival rates. The cancer stem cell (CSC) theory provides a tractable explanation for the observation that recurrences occur despite dramatic responses to upfront chemotherapy. Preclinical studies demonstrated that inhibition of the mechanistic target of rapamycin (mTOR) sensitizes the CSC population to chemotherapy.
Methods
Here we present the results of the Phase II portion of a Phase I/II clinical trial that aimed to overcome the chemoresistance of sarcoma CSC by combining the mTOR inhibitor temsirolimus (20Â mg/m2 weekly) with the chemotherapeutic agent liposomal doxorubicin (30Â mg/m2 monthly).
Results
Fifteen patients with relapsed/refractory sarcoma were evaluable at this recommended Phase 2 dose level. The median progression free survival was 315 days (range 27–799). Response rate, defined as stable disease or better for 60 days, was 53%. Nine of the patients had been previously treated with doxorubicin. Therapy was well tolerated. In a small number of patients, pre- and post- treatment tumor biopsies were available for assessment of ALDH expression as a marker of CSCs and showed a correlation between response and decreased ALDH expression. We also found a correlation between biopsy-proven inhibition of mTOR and response.
Conclusions
Our study adds to the literature supporting the addition of mTOR inhibition to chemotherapy agents for the treatment of sarcomas, and proposes that a mechanism by which mTOR inhibition enhances the efficacy of chemotherapy may be through sensitizing the chemoresistant CSC population. Further study, ideally with pre- and post-therapy assessment of ALDH expression in tumor cells, is warranted.
Trial registration The trial was registered on clinicaltrials.gov (NCT00949325) on 30 July 2009. http://www.editorialmanager.com/csrj/default.asp
Cyclophosphamide-Induced Cystitis Increases Bladder CXCR4 Expression and CXCR4-Macrophage Migration Inhibitory Factor Association
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine involved in cystitis and a non-cognate ligand of the chemokine receptor CXCR4 in vitro. We studied whether CXCR4-MIF associations occur in rat bladder and the effect of experimental cystitis. METHODS AND FINDINGS: Twenty male rats received saline or cyclophosphamide (40 mg/kg; i.p.; every 3(rd) day) to induce persistent cystitis. After eight days, urine was collected and bladders excised under anesthesia. Bladder CXCR4 and CXCR4-MIF co-localization were examined with immunhistochemistry. ELISA determined MIF and stromal derived factor-1 (SDF-1; cognate ligand for CXCR4) levels. Bladder CXCR4 expression (real-time RTC-PCR) and protein levels (Western blotting) were examined. Co-immunoprecipitations studied MIF-CXCR4 associations.Urothelial basal and intermediate (but not superficial) cells in saline-treated rats contained CXCR4, co-localized with MIF. Cyclophosphamide treatment caused: 1) significant redistribution of CXCR4 immunostaining to all urothelial layers (especially apical surface of superficial cells) and increased bladder CXCR4 expression; 2) increased urine MIF with decreased bladder MIF; 3) increased bladder SDF-1; 4) increased CXCR4-MIF associations. CONCLUSIONS: These data demonstrate CXCR4-MIF associations occur in vivo in rat bladder and increase in experimental cystitis. Thus, CXCR4 represents an alternative pathway for MIF-mediated signal transduction during bladder inflammation. In the bladder, MIF may compete with SDF-1 (cognate ligand) to activate signal transduction mediated by CXCR4
Prediction of Emerging Technologies Based on Analysis of the U.S. Patent Citation Network
The network of patents connected by citations is an evolving graph, which
provides a representation of the innovation process. A patent citing another
implies that the cited patent reflects a piece of previously existing knowledge
that the citing patent builds upon. A methodology presented here (i) identifies
actual clusters of patents: i.e. technological branches, and (ii) gives
predictions about the temporal changes of the structure of the clusters. A
predictor, called the {citation vector}, is defined for characterizing
technological development to show how a patent cited by other patents belongs
to various industrial fields. The clustering technique adopted is able to
detect the new emerging recombinations, and predicts emerging new technology
clusters. The predictive ability of our new method is illustrated on the
example of USPTO subcategory 11, Agriculture, Food, Textiles. A cluster of
patents is determined based on citation data up to 1991, which shows
significant overlap of the class 442 formed at the beginning of 1997. These new
tools of predictive analytics could support policy decision making processes in
science and technology, and help formulate recommendations for action
Comparison of plasma and CSF biomarkers in predicting cognitive decline
OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer\u27s disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.
METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over a maximum of 6 years as predicted by the fluid biomarkers.
RESULTS: Analyses included 371 cognitively normal participants, aged 72.7 ± 5.2 years (mean ± standard deviation) with an average length of follow-up of 3.9 ± 1.6 years. Standardized concentrations of biomarkers were associated with annualized cognitive change: plasma Aβ42/Aβ40, 0.014 standard deviations (95% confidence intervals 0.002 to 0.026); CSF Aβ42/Aβ40, 0.020 (0.008 to 0.032); plasma Nfl, -0.018 (-0.030 to -0.005); and CSF NfL, -0.024 (-0.036 to -0.012). Power analyses estimated that 266 individuals in each treatment arm would be needed to detect a 50% slowing of decline if identified by abnormal plasma measures versus 229 for CSF measures.
INTERPRETATION: Both plasma and CSF measures of Aβ42/Aβ40 and NfL predicted cognitive decline. A clinical trial that enrolled individuals based on abnormal plasma Aβ42/Aβ40 and NfL levels would require only a marginally larger cohort than if CSF measures were used
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