1,355 research outputs found
Gene amplifications associated with the development of hormone- resistant prostate cancer
Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential.
Experimental Design: We analyzed 38 paired (prehormone/posthormone resistance) prostate cancer samples using the Vysis GenoSensor. Archival microdissected tumor DNA was extracted, amplified, labeled, and hybridized to Amplione I DNA microarrays containing 57 oncogenes.
Results: Genetic instability increased during progression from hormone-sensitive to hormone-resistant cancer (P = 0.008). Amplification frequencies of 15 genes (TERC, MYBL3, HRAS, PI3KCA, JUNB, LAMC2, RAF1, MYC, GARP, SAS, FGFR1, PGY1, MYCL1, MYB, FGR) increased by greater than 10% during hormone escape. Receptor tyrosine kinases were amplified in 73% of cases; this was unrelated to development of hormone resistance. However, downstream receptor tyrosine kinase signaling pathways showed increased amplification rates in resistant tumors for the mitogen-activated protein kinase (FGR/Src-2, HRAS, and RAF1; P = 0.005) and phosphatidylinositol 3'-kinase pathways (FGR/ Src-2, PI3K, and Akt; P = 0.046). Transcription factors regulated by these pathways were also more frequently amplified after escape (MYC family: 21% before versus 63% after, P = 0.027; MYB family: 26 % before versus 53 % after, P = 0.18).
Conclusions: Development of clinical hormone escape is linked to phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. These pathways may function independently of the androgen receptor or via androgen receptor activation by phosphorylation, providing novel therapeutic targets
An investigation into self-reported foot and lower limb problems associated with systemic lupus erythematosus (SLE): a research proposal
Systemic lupus erythematosus (SLE) can manifest in the lower limb with joint and muscle pains and in severe cases, disorganisation of the joints and tendon rupture. In the foot and lower limb, Raynaud’s phenomenon and other circulatory problems have been reported and may be associated with loss of sensation or altered pain perception. Associated with impaired peripheral neurovascular function are changes in tissue viability leading to either callus formation or thinning of the skin and ulceration. Many medications used to manage SLE can impact on the person’s resistance to infections and consequently fungal, bacterial or viral infections can spread rapidly and persist. Although there is some evidence for this range of problems occurring in the foot, it is not known how prevalent they are, what interaction there is between problems, and how these impact upon a person’s health related quality of life (HRQoL). Thus, the main aim of this study is to determine the self-reported foot and lower limb problems experienced by people with SLE. A secondary aim is to explore the impact that the identified foot and lower complications may have upon patients with SLE. It is anticipated that this research will highlight areas of potential health care need and thus can be used to inform recommendations about foot health care for this patient group and the focus of future research
Is there evidence to support multidisciplinary healthcare working in rheumatology? A systematic review of the literature
A study of the effects of metallic pins on SAR using a Specific Anthropomorphic Mannequin (SAM) Head Phantom
This paper presents the effects of facial metallic pins on the
Specific Absorption Rate (SAR) in the head, when radiated
by a microwave source placed in front of the face. A Specific
Anthropomorphic Mannequin (SAM) is adapted for use with
a DASY4 and a digitised SAM head is modelled using inhouse
Finite-Difference Time-Domain (FDTD) code,
enabling comparisons between measurements and
simulations. A continuous wave (CW) half-wave dipole is
placed in front of the face, representing a communications
enabled personal data assistant mobile communications
equipment (PDAMCE). Parametric studies have shown that
metallic pins that are roughly half a wavelength long placed
along the eyebrow, increase the 1g and 10g SARs at 900MHz
by around five fold. A greater than five fold increase is seen
at 1800MHz. Measurements show very good agreement with
simulations
Specific Absorption Rates in the human head due to circular metallic earrings at 1800MHz
This paper investigates Specific Absorption Rates (SAR) in the human head due to circular metallic
earrings at 1800MHz. A Finite-Difference Time-Domain (FDTD) code was used to analyse different sizes and
positions of circular earrings near a homogenous cubic phantom. Results showed good agreement with
measurements using the flat section of the SAM twin phantom with the DASY4 measurement system. The
excitation was a half wave dipole. Metallic loops with a circumference of approximately one wavelength and
positioned 14mm away from the phantom increased the 10g SAR by 5 times. The FDTD code has also been
used to analyse the effect of metallic earrings when ‘pierced’ through the ear of an anatomically realistic digital
human head based on the Visible Human Project. The head is not symmetric and both ears were considered to
allow comparison between different heads. The shape of the ear and the size of the earring were found to be
very significant when earrings were hung from the human ear
The SAR effects of popular jewellery on the human head
This paper investigates the effects of metallic jewellery on the
SAR in the human head. A CW dipole is placed in front of the
head to represent a mobile enabled personal data assistant.
The FDTD method has been used to simulate an eyebrow ring
near a homogeneous SAM phantom at 1.8GHz.
Measurements were made on the Loughborough SAM head
with the DASY4 measurement system. Simulations were also
made with eyebrow rings on the surface of the skin and
pierced through the eyebrow of a heterogeneous anatomically
realistic human head. Common sizes of eyebrow ring and
eyebrow stud have been considered over the frequency range
0.6 to 4.6GHz. Jewellery which was small compared to a
wavelength had little effect on the SAR in the head
Impact of high wind penetration on variability of unserved energy in power system adequacy
This paper presents results on variability of out-turn shortfalls about the expected value indices which are usually presented in resource adequacy studies, for a range of Loss of Load Expectation (LOLE) levels and installed wind capacities in a test system generally representative of future Great Britain system scenarios. While the details of results will clearly vary between systems, one very general conclusion is possible. In the results presented, for a given LOLE level, the probability of very severe out-turn in a future peak season is much greater at high installed wind capacity. Thus for this system, as the installed wind capacity increases, a constant level of LOLE cannot be taken as an indicator of an unchanging overall risk profile of the system. This further demonstrates that in any system, LOLE cannot be assumed to be a good summary statistic of risk profile as the installed variable generation (VG) capacity increases, and that it might be necessary to reconsider the near-universal use of expected value risk indices as the main headline indices in utility adequacy studies
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