A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer

A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. Systematic searching (upto April 2005) identified seven randomised controlled trials. One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline. Two other chemotherapy regimens that included docetaxel with estramustine also showed improved outcomes in comparison with mitoxantrone plus prednisone. Three trials that compared mitoxantrone plus corticosteroids with corticosteroids alone were identified and their results for overall survival combined, which showed very little difference between the two groups. The addition of clodronate to mitoxantrone plus prednisone showed no significant differences in comparison with mitoxantrone plus prednisone alone. The evidence suggests that chemotherapy regimens containing 3-weekly docetaxel are superior to mitoxantrone or corticosteroids alone

Exploring Relations Between BCG and Cluster Properties in the SPectroscopic IDentification of eROSITA Sources Survey from 0.05<z<0.30.05 < z < 0.3

We present a sample of 329 low to intermediate redshift ($0.05 < z < 0.3$) brightest cluster galaxies (BCGs) in X-ray selected clusters from the SPectroscopic IDentification of eRosita Sources (SPIDERS) survey, a spectroscopic survey within Sloan Digital Sky Survey-IV (SDSS-IV). We define our BCGs by simultaneous consideration of legacy X-ray data from ROSAT, maximum likelihood outputs from an optical cluster-finder algorithm and visual inspection. Using SDSS imaging data, we fit S\'ersic profiles to our BCGs in three bands (\textit{g}, \textit{r}, \textit{i}) with \textsc{SIGMA}, a \textsc{GALFIT}-based software wrapper. We examine the reliability of our fits by running our pipeline on ${\sim}10^{4}$ psf-convolved model profiles injected into 8 random cluster fields, we then use the results of this analysis to create a robust subsample of 198 BCGs. We outline three cluster properties of interest: overall cluster X-ray luminosity ($L_{X}$), cluster richness as estimated by \textsc{redMaPPer} ($\lambda$) and cluster halo mass ($M_{200}$), which is estimated via velocity dispersion. In general, there are significant correlations with BCG stellar mass between all three environmental properties, but no significant trends arise with either S\'ersic index or effective radius. There is no major environmental dependence on the strength of the relation between effective radius and BCG stellar mass. Stellar mass therefore arises as the most important factor governing BCG morphology. Our results indicate that our sample consists of a large number of relaxed, mature clusters containing broadly homogeneous BCGs up to $z \sim 0.3$, suggesting that there is little evidence for much ongoing structural evolution for BCGs in these systems

The impact of predation by marine mammals on Patagonian toothfish longline fisheries

Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of “depredation hot spots” can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources

A randomized comparison between three types of irrigating fluids during transurethral resection in benign prostatic hyperplasia

<p>Abstract</p> <p>Background</p> <p>Central nervous system changes, circulatory and electrolyte imbalances are the main complications of endoscopic transurethral resection of the prostate (TURP) which is known as transurethral resection (TUR) syndrome, which occurs as result of excessive absorption of irrigating fluid. We compare glycine 1.5% versus glucose 5% and normal saline 0.9% as irrigating solutions during TURP in patients with moderate to severe bladder outlet obstruction due to benign prostatic hyperplasia (BPH).</p> <p>Methods</p> <p>Three hundred sixty patients with symptomatic BPH were randomized into a prospective, controlled trial comparing the three irrigation modalities. One-hundred twenty patients used glycine 1.5% solution as irrigating fluid (glycine group), 120 patients used glucose 5% solution (glucose group) and 120 patients used normal saline 0.9% solution (saline group). Patient's demographics, operation time, hospital stay, postoperative amino acid glycine assay, postoperative serum cardiac troponin I and perioperative complications were noted.</p> <p>Results</p> <p>No difference was found between the groups in the immediate postoperative levels of hemoglobin and hematocrite. A high glycine level was associated with the TUR syndrome. Seventeen patients had TUR syndrome; all were in glycine group and they had the highest postoperative amino acid glycine levels. Slight increase in serum sodium (142.6 ± 12.6 mmol/l) was detected in saline group. Transient Hyperglycemia (170 ± 35.9 mg/dl) and hypokalemia (3.67 ± 0.92 mmol/l) occurred in the immediate postoperative period in the glucose group.</p> <p>Conclusion</p> <p>Endoscopic TURP performed using either glucose 5% or saline 0.9% irrigating solution during and after surgery is associated with lower incidence of TUR syndrome, lower catheterization period, shorter hospital stay and no cardiac toxicity in comparison with glycine 1.5% solution.</p> <p>Trial Registration</p> <p>This clinical trail had been approved and registered in PACT Registry; with identification number for the registry is ATMR2010010001793131.</p

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Attachment styles and personal growth following romantic breakups: The mediating roles of distress, rumination, and tendency to rebound

© 2013 Marshall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.The purpose of this research was to examine the associations of attachment anxiety and avoidance with personal growth following relationship dissolution, and to test breakup distress, rumination, and tendency to rebound with new partners as mediators of these associations. Study 1 (N = 411) and Study 2 (N = 465) measured attachment style, breakup distress, and personal growth; Study 2 additionally measured ruminative reflection, brooding, and proclivity to rebound with new partners. Structural equation modelling revealed in both studies that anxiety was indirectly associated with greater personal growth through heightened breakup distress, whereas avoidance was indirectly associated with lower personal growth through inhibited breakup distress. Study 2 further showed that the positive association of breakup distress with personal growth was accounted for by enhanced reflection and brooding, and that anxious individuals’ greater personal growth was also explained by their proclivity to rebound. These findings suggest that anxious individuals’ hyperactivated breakup distress may act as a catalyst for personal growth by promoting the cognitive processing of breakup-related thoughts and emotions, whereas avoidant individuals’ deactivated distress may inhibit personal growth by suppressing this cognitive work

Instrument development, data collection, and characteristics of practices, staff, and measures in the Improving Quality of Care in Diabetes (iQuaD) Study

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