130 research outputs found
Enzalutamide in chemo-naïve castration-resistant prostate cancer: effective for most but not for all
No full textContinued research in the treatment of castration-resistant prostate cancer (CRPC) has allowed for a clearer understanding of this disease entity and further treatment advances. In a study recently published by Beer et al. [1] in the New England Journal of Medicine, another advance to treatment was demonstrated for the androgen receptor (AR) signaling inhibitor, enzalutamide, in patients with chemotherapy-naïve metastatic CRPC. Although a large majority of patients responded favorably to enzalutamide in the prechemotherapy setting, a small but significant proportion of patients demonstrated no meaningful benefit to this agent. This highlights an important concept in the understanding of this disease: inherent and acquired resistance to AR-targeting therapies
New role of fat-free mass in cancer risk linked with genetic predisposition.
No full textCancer risk is associated with the widely debated measure body mass index (BMI). Fat mass and fat-free mass measurements from bioelectrical impedance may further clarify this association. The UK Biobank is a rare resource in which bioelectrical impedance and BMI data was collected on ~ 500,000 individuals. Using this dataset, a comprehensive analysis using regression, principal component and genome-wide genetic association, provided multiple levels of evidence that increasing whole body fat (WBFM) and fat-free mass (WBFFM) are both associated with increased post-menopausal breast cancer risk, and colorectal cancer risk in men. WBFM was inversely associated with prostate cancer. We also identified rs615029[T] and rs1485995[G] as associated in independent analyses with both PMBC (p = 1.56E-17 and 1.78E-11) and WBFFM (p = 2.88E-08 and 8.24E-12), highlighting splice variants of the intriguing long non-coding RNA CUPID1 (LINC01488) as a potential link between PMBC risk and fat-free mass
Chandra x-ray analysis of the massive high-redshift galaxy clusters C1J1113.1-2615
No full textWe present an analysis of Chandra observations of two high-redshift clusters of galaxies, Cl J1113.1-2615 at z = 0.725 and Cl J0152.7-1357 at z = 0.833. We find Cl J1113.1-2615 to be morphologically relaxed with a temperature of kT = 4.3(-0.4)(+0.5) keV and a mass (within the virial radius) of 4.3(-0.7)(+0.8) x 10(14) M-circle dot. Cl J0152.7-1357, by contrast, is resolved into a northern and southern subcluster, each massive and X-ray luminous, in the process of merging. The temperatures of the subclusters are found to be 5.5(-0.8)(+0.9) and 5.2(-0.9)(+1.1) keV, respectively, and we estimate their respective masses to be 6.1(-1.5)(+1.7) x 10(14) and 5.2(-1.4)(+1.8) x 10(14) M-circle dot within the virial radii. A dynamical analysis of the system shows that the subclusters are likely to be gravitationally bound. If the subclusters merge, they will form a system with a mass similar to that of the Coma Cluster. Two-dimensional modeling of the X-ray surface brightness reveals excess emission between the subclusters, suggestive, but not conclusive, evidence of a shock front. We make a first attempt at measuring the cluster M-T relation at z approximate to 0.8 and find no evolution in its normalization, supporting the previous assumption of an unevolving M-T relation when constraining cosmological parameters from cluster evolution studies. A comparison of the cluster properties with those of nearby systems also finds little or no evolution in the L-T relation, the gas fraction-T relation, the beta-T relation, or the metallicity. These results suggest that, in at least some massive clusters, the hot gas was in place, and containing its metals, at z approximate to 0.8 and thus that the clusters were assembled at redshifts significantly higher than z = 0.8, as predicted in low-Omega(M) models. We also highlight the need to correct for the degradation of the Chandra ACIS low-energy quantum efficiency in high-redshift cluster studies when the low-energy absorption is often assumed to be the Galactic value, rather than measured
An XMM-Newton observation of the massive, relaxed galaxy cluster ClJ1226.9+3332 at z=0.89
No full textA detailed X-ray analysis of an XMM-Newton observation of the high-redshift (z=0.89) galaxy cluster ClJ1226.9+3332 is presented. The X-ray temperature is found to be 11.5{+1.1}{-0.9}keV, the highest X-ray temperature of any cluster at z>0.6. In contrast to MS1054-0321, the only other very hot cluster currently known at z>0.8, ClJ1226.9+3332 features a relaxed X-ray morphology, and its high overall gas temperature is not caused by one or several hot spots. The system thus constitutes a unique example of a high redshift, high temperature, relaxed cluster, for which the usual hydrostatic equilibrium assumption, and the X-ray mass is most reliable. A temperature profile is constructed (for the first time at this redshift) and is consistent with the cluster being isothermal out to 45% of the virial radius. Within the virial radius (corresponding to a measured overdensity of a factor of 200), a total mass of (1.4+/-0.5)*10^15 M_solar is derived, with a gas mass fraction of 12+/-5%. The bolometric X-ray luminosity is (5.3+/-0.2)*10^45 erg/s. The probabilities of finding a cluster of this mass within the volume of the discovery X-ray survey are 8*10^{-5} for Omega_M=1 and 0.64 for Omega_M=0.3, making Omega_M=1 highly unlikely. The entropy profile suggests that entropy evolution is being observed. The metal abundance (of Z=0.33{+0.14}{-0.10} Z_solar), gas mass fraction, and gas distribution are consistent with those of local clusters; thus the bulk of the metals were in place by z=0.89
Mechanism and Management of Checkpoint Inhibitor-Related Toxicities in Genitourinary Cancers
No full textSIMPLE SUMMARY: Immune therapy using checkpoint inhibitors has been increasing in genitourinary cancers for the past decade, starting with monotherapy in renal cell carcinoma and urothelial carcinoma to now include many first-line combinations. More combinations and FDA/EMA indications are undoubtedly on the horizon. An increasing number of patients will be treated with these therapies in the future resulting in a significant increase in the prevalence of immune mediated toxicities. This manuscript focuses on the current understanding of immunotherapy related adverse effects in genitourinary malignancies encountered with the use of immune checkpoint inhibitors. ABSTRACT: The use of immune checkpoint inhibitors (ICIs) is rapidly increasing as more combinations and clinical indications are approved in the field of genitourinary malignancies. Most immunotherapeutic agents being approved are for the treatment of renal cell carcinoma and bladder cancer, which mainly involve PD-1/PD-L1 and CTLA-4 pathways. There is an ongoing need for recognizing and treating immunotherapy-related autoimmune adverse effects (irAEs). This review aims to critically appraise the recent literature on the mechanism, common patterns, and treatment recommendations of irAEs in genitourinary malignancies. We review the epidemiology of these adverse effects as well as general treatment strategies. The underlying mechanisms will also be discussed. Diagnostic considerations including differential diagnosis are also included in this review
The Effect of a Dairy-Based Recovery Beverage on Post-Exercise Appetite and Energy Intake in Active Females
No full textThis study was designed to assess the effect of a dairy-based recovery beverage on post-exercise appetite and energy intake in active females. Thirteen active females completed 3 trials in a crossover design. Participants completed 60 min of cycling at 65% V̇O2peak, before a 120 min recovery period. On completion of cycling, participants consumed a commercially available dairy-based beverage (DBB), a commercially available carbohydrate beverage (CHO), or a water control (H2O). Non-esterified fatty acids, glucose and appetite-related peptides alongside measures of subjective appetite were sampled at baseline and at 30 min intervals during recovery. At 120 min, energy intake was assessed in the laboratory by ad libitum assessment, and in the free-living environment by weighed food record for the remainder of the study day. Energy intake at the ad libitum lunch was lower after DBB compared to H2O (4.43 ± 0.20, 5.58 ± 0.41 MJ respectively; P = .046; [95% CI: -2.28, -0.20 MJ]), but was not different to CHO (5.21 ± 0.46 MJ), with no difference between trials thereafter. Insulin and GLP-17-36 were higher following DBB compared to H2O (P = .015 and P = .001, respectively) but not to CHO (P = 1.00 and P = .146, respectively). In addition, glucagon was higher following DBB compared to CHO (P = .008) but not to H20 (P = .074). The results demonstrate that where DBB consumption may manifest in accelerated recovery, this may be possible without significantly affecting total energy intake and subsequent appetite-related responses relative to a CHO beverage
"A Symbol of the New African": Drum magazine, popular culture and the formation of black urban subjectivity in 1950s South Africa.
No full textPhDThis thesis examines the emergence of black urban subjectivity in South Africa
during the 1950s, focussing on the ways in which popular American genres were
utilised in the construction of black urban identities that served as a means of
resistance to apartheid. At the centre of this process was Drum magazine:
founded in South Africa in 1951 , it became the largest selling magazine on the
African continent in 1956. Drum's success was due to the way in which it
enabled the relocation of black identity from the "traditional" towards the
"modern'. The 1940s gave rise to widespread migration of black South Africans
from rural to urban areas and this newly urbanised community was seeking
models of black urban identity. Yet the Nationalist government was attempting
to curtail the emergence of a black urban proletariat, which posed a threat to
white political supremacy. Through apartheid legislation black identity was
constructed as essentially tribal and rural. As a means of resisting this, urbanised
black South Africans turned to, and appropriated, readily available forms of
American culture. Drum published Americanised images and stories: gangsters,
black detectives, black comic heroes, and pulp romances. This popular material
appeared alongside some of the finest investigative journalism ever published.
While Drum magazine is widely acknowledged as having provided a platform
for the emergence of black South African writing in English, its popular content
has been dismissed by critics as apolitical escapism, imitation and capitulation to
American culture. This thesis challenges the dismissal of the popular that has
dominated analyses of Drum since the 1960s, arguing that such a position denies
the agency of local writers and audiences. My analysis reveals that American
forms were adopted in critically discerning ways and chosen for their ability to
convey local meaning and create positions from which to resist aparthei
Incidence of Immune-Related Adverse Events with Program Death Receptor-1- and Program Death Receptor-1 Ligand-Directed Therapies in Genitourinary Cancers
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