274 research outputs found
International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate : A meta-analysis of 1446 patients
OBJECTIVE: To review pooled phase II data to identify features of different regimens of intermittent hormone therapy (IHT), developed to reduce the morbidity of treating metastatic prostate cancer, and which carries a theoretical advantage of delaying the onset of androgen-independent prostate cancer, (AIPC) that are associated with success, highlighting features which require exploration with prospective trials to establish the best strategies for using this treatment. METHODS: Individual data were collated on 1446 patients with adequate information, from 10 phase II studies with >50 cases, identified through Pubmed. RESULTS: Univariate and multivariate Cox proportional hazard models were developed to predict treatment success with a high degree of statistical success. The prostate-specific antigen (PSA) nadir, the PSA threshold to restart treatment, and medication type and duration, were important predictors of outcome. CONCLUSIONS: The duration of biochemical remission after a period of HT is a durable early indicator of how rapidly AIPC and death will occur, and will make a useful endpoint in future trials to investigate the best ways to use IHT based on the important treatment cycling variables described above. Patients spent a mean of 39% of the time off treatment. The initial PSA level and PSA nadir allow the identification of patients with prostate cancer in whom it might be possible to avoid radical therapy.Peer reviewe
Response of Degarelix treatment in human prostate cancer monitored by HR-MAS 1H NMR spectroscopy.
INTRODUCTION: The androgen receptor (AR) is the master regulator of prostate cancer cell metabolism. Degarelix is a novel gonadotrophin-releasing hormone blocker, used to decrease serum androgen levels in order to treat advanced human prostate cancer. Little is known of the rapid metabolic response of the human prostate cancer tissue samples to the decreased androgen levels. OBJECTIVES: To investigate the metabolic responses in benign and cancerous tissue samples from patients after treatment with Degarelix by using HRMAS 1H NMR spectroscopy. METHODS: Using non-destructive HR-MAS 1H NMR spectroscopy we analysed the metabolic changes induced by decreased AR signalling in human prostate cancer tissue samples. Absolute concentrations of the metabolites alanine, lactate, glutamine, glutamate, citrate, choline compounds [t-choline = choline + phosphocholine (PC) + glycerophosphocholine (GPC)], creatine compounds [t-creatine = creatine (Cr) + phosphocreatine (PCr)], taurine, myo-inositol and polyamines were measured in benign prostate tissue samples (n = 10), in prostate cancer specimens from untreated patients (n = 7) and prostate cancer specimens from patients treated with Degarelix (n = 6). RESULTS: Lactate, alanine and t-choline concentrations were significantly elevated in high-grade prostate cancer samples when compared to benign samples in untreated patients. Decreased androgen levels resulted in significant decreases of lactate and t-choline concentrations in human prostate cancer biopsies. CONCLUSIONS: The reduced concentrations of lactate and t-choline metabolites due to Degarelix could in principle be monitored by in vivo 1H MRS, which suggests that it would be possible to monitor the effects of physical or chemical castration in patients by that non-invasive method.We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11306-016-1055-0
Tuning graphitic oxide for initiator- and metal-free aerobic epoxidation of linear alkenes
Graphitic oxide has potential as a carbocatalyst for a wide range of reactions. Interest in this material has risen enormously due to it being a precursor to graphene via the chemical oxidation of graphite. Despite some studies suggesting that the chosen method of graphite oxidation can influence the physical properties of the graphitic oxide, the preparation method and extent of oxidation remain unresolved for catalytic applications. Here we show that tuning the graphitic oxide surface can be achieved by varying the amount and type of oxidant. The resulting materials differ in level of oxidation, surface oxygen content and functionality. Most importantly, we show that these graphitic oxide materials are active as unique carbocatalysts for low-temperature aerobic epoxidation of linear alkenes in the absence of initiator or metal. An optimum level of oxidation is necessary and materials produced via conventional permanganate-based methods are far from optimal
Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder
A pathfinder version of CHIME (the Canadian Hydrogen Intensity Mapping
Experiment) is currently being commissioned at the Dominion Radio Astrophysical
Observatory (DRAO) in Penticton, BC. The instrument is a hybrid cylindrical
interferometer designed to measure the large scale neutral hydrogen power
spectrum across the redshift range 0.8 to 2.5. The power spectrum will be used
to measure the baryon acoustic oscillation (BAO) scale across this poorly
probed redshift range where dark energy becomes a significant contributor to
the evolution of the Universe. The instrument revives the cylinder design in
radio astronomy with a wide field survey as a primary goal. Modern low-noise
amplifiers and digital processing remove the necessity for the analog
beamforming that characterized previous designs. The Pathfinder consists of two
cylinders 37\,m long by 20\,m wide oriented north-south for a total collecting
area of 1,500 square meters. The cylinders are stationary with no moving parts,
and form a transit instrument with an instantaneous field of view of
100\,degrees by 1-2\,degrees. Each CHIME Pathfinder cylinder has a
feedline with 64 dual polarization feeds placed every 30\,cm which
Nyquist sample the north-south sky over much of the frequency band. The signals
from each dual-polarization feed are independently amplified, filtered to
400-800\,MHz, and directly sampled at 800\,MSps using 8 bits. The correlator is
an FX design, where the Fourier transform channelization is performed in FPGAs,
which are interfaced to a set of GPUs that compute the correlation matrix. The
CHIME Pathfinder is a 1/10th scale prototype version of CHIME and is designed
to detect the BAO feature and constrain the distance-redshift relation.Comment: 20 pages, 12 figures. submitted to Proc. SPIE, Astronomical
Telescopes + Instrumentation (2014
Potential health impacts of heavy metals on HIV-infected population in USA.
Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes
The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer.
The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression).We thank CRUK, The NIHR, The Academy of Medical Sciences(RG:63397) and the National Cancer Research Prostate Cancer: Mechanisms of Progression and Treatment (ProMPT) collaborative (G0500966/75466), Hutchison Whampoa Limited, the Human Research Tissue Bank (Addenbrooke’s Hospital, supported by the NIHR Cambridge BRC), and Cancer Research UK
The Correlation between Running Economy and Maximal Oxygen Uptake: Cross-Sectional and Longitudinal Relationships in Highly Trained Distance Runners
A positive relationship between running economy and maximal oxygen uptake (V̇O2max) has been postulated in trained athletes, but previous evidence is equivocal and could have been confounded by statistical artefacts. Whether this relationship is preserved in response to running training (changes in running economy and V̇O2max) has yet to be explored. This study examined the relationships of (i) running economy and V̇O2max between runners, and (ii) the changes in running economy and V̇O2max that occur within runners in response to habitual training. 168 trained distance runners (males, n = 98, V̇O2max 73.0 ± 6.3 mLkg-1min-1; females, n = 70, V̇O2max 65.2 ± 5.9 mL kg-1min-1) performed a discontinuous submaximal running test to determine running economy (kcalkm-1). A continuous incre-mental treadmill running test to volitional exhaustion was used to determine V̇O2max 54 par-ticipants (males, n = 27; females, n = 27) also completed at least one follow up assessment. Partial correlation analysis revealed small positive relationships between running economy and V̇O2max (males r = 0.26, females r = 0.25; P<0.006), in addition to moderate positive re-lationships between the changes in running economy and V̇O2max in response to habitual training (r = 0.35; P<0.001). In conclusion, the current investigation demonstrates that only a small to moderate relationship exists between running economy and V̇O2max in highly trained distance runners. With>85 % of the variance in these parameters unexplained by this relationship, these findings reaffirm that running economy and V̇O2max are primarily determined independently
Haloes gone MAD: The Halo-Finder Comparison Project
[abridged] We present a detailed comparison of fundamental dark matter halo
properties retrieved by a substantial number of different halo finders. These
codes span a wide range of techniques including friends-of-friends (FOF),
spherical-overdensity (SO) and phase-space based algorithms. We further
introduce a robust (and publicly available) suite of test scenarios that allows
halo finder developers to compare the performance of their codes against those
presented here. This set includes mock haloes containing various levels and
distributions of substructure at a range of resolutions as well as a
cosmological simulation of the large-scale structure of the universe. All the
halo finding codes tested could successfully recover the spatial location of
our mock haloes. They further returned lists of particles (potentially)
belonging to the object that led to coinciding values for the maximum of the
circular velocity profile and the radius where it is reached. All the finders
based in configuration space struggled to recover substructure that was located
close to the centre of the host halo and the radial dependence of the mass
recovered varies from finder to finder. Those finders based in phase space
could resolve central substructure although they found difficulties in
accurately recovering its properties. Via a resolution study we found that most
of the finders could not reliably recover substructure containing fewer than
30-40 particles. However, also here the phase space finders excelled by
resolving substructure down to 10-20 particles. By comparing the halo finders
using a high resolution cosmological volume we found that they agree remarkably
well on fundamental properties of astrophysical significance (e.g. mass,
position, velocity, and peak of the rotation curve).Comment: 27 interesting pages, 20 beautiful figures, and 4 informative tables
accepted for publication in MNRAS. The high-resolution version of the paper
as well as all the test cases and analysis can be found at the web site
http://popia.ft.uam.es/HaloesGoingMA
The state of the Martian climate
60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
LSST: from Science Drivers to Reference Design and Anticipated Data Products
(Abridged) We describe here the most ambitious survey currently planned in
the optical, the Large Synoptic Survey Telescope (LSST). A vast array of
science will be enabled by a single wide-deep-fast sky survey, and LSST will
have unique survey capability in the faint time domain. The LSST design is
driven by four main science themes: probing dark energy and dark matter, taking
an inventory of the Solar System, exploring the transient optical sky, and
mapping the Milky Way. LSST will be a wide-field ground-based system sited at
Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m
effective) primary mirror, a 9.6 deg field of view, and a 3.2 Gigapixel
camera. The standard observing sequence will consist of pairs of 15-second
exposures in a given field, with two such visits in each pointing in a given
night. With these repeats, the LSST system is capable of imaging about 10,000
square degrees of sky in a single filter in three nights. The typical 5
point-source depth in a single visit in will be (AB). The
project is in the construction phase and will begin regular survey operations
by 2022. The survey area will be contained within 30,000 deg with
, and will be imaged multiple times in six bands, ,
covering the wavelength range 320--1050 nm. About 90\% of the observing time
will be devoted to a deep-wide-fast survey mode which will uniformly observe a
18,000 deg region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . The
remaining 10\% of the observing time will be allocated to projects such as a
Very Deep and Fast time domain survey. The goal is to make LSST data products,
including a relational database of about 32 trillion observations of 40 billion
objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures
available from https://www.lsst.org/overvie
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