119 research outputs found
Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels.
The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level
Optical Properties of Deep Ice at the South Pole - Absorption
We discuss recent measurements of the wavelength-dependent absorption
coefficients in deep South Pole ice. The method uses transit time distributions
of pulses from a variable-frequency laser sent between emitters and receivers
embedded in the ice. At depths of 800 to 1000 m scattering is dominated by
residual air bubbles, whereas absorption occurs both in ice itself and in
insoluble impurities. The absorption coefficient increases approximately
exponentially with wavelength in the measured interval 410 to 610 nm. At the
shortest wavelength our value is about a factor 20 below previous values
obtained for laboratory ice and lake ice; with increasing wavelength the
discrepancy with previous measurements decreases. At around 415 to 500 nm the
experimental uncertainties are small enough for us to resolve an extrinsic
contribution to absorption in ice: submicron dust particles contribute by an
amount that increases with depth and corresponds well with the expected
increase seen near the Last Glacial Maximum in Vostok and Dome C ice cores. The
laser pulse method allows remote mapping of gross structure in dust
concentration as a function of depth in glacial ice.Comment: 26 pages, LaTex, Accepted for publication in Applied Optics. 9
figures, not included, available on request from [email protected]
The AMANDA Neutrino Telescope and the Indirect Search for Dark Matter
With an effective telescope area of order 10^4 m^2, a threshold of ~50 GeV
and a pointing accuracy of 2.5 degrees, the AMANDA detector represents the
first of a new generation of high energy neutrino telescopes, reaching a scale
envisaged over 25 years ago. We describe its performance, focussing on the
capability to detect halo dark matter particles via their annihilation into
neutrinos.Comment: Latex2.09, 16 pages, uses epsf.sty to place 15 postscript figures.
Talk presented at the 3rd International Symposium on Sources and Detection of
Dark Matter in the Universe (DM98), Santa Monica, California, Feb. 199
The AMANDA Neutrino Telescope
With an effective telescope area of order m for TeV neutrinos, a
threshold near 50 GeV and a pointing accuracy of 2.5 degrees per muon
track, the AMANDA detector represents the first of a new generation of high
energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We
describe early results on the calibration of natural deep ice as a particle
detector as well as on AMANDA's performance as a neutrino telescope.Comment: 12 pages, Latex2.09, uses espcrc2.sty and epsf.sty, 13 postscript
files included. Talk presented at the 18th International Conference on
Neutrino Physics and Astrophysics (Neutrino 98), Takayama, Japan, June 199
The AMANDA Neutrino Telescope: Principle of Operation and First Results
AMANDA is a high-energy neutrino telescope presently under construction at
the geographical South Pole. In the Antarctic summer 1995/96, an array of 80
optical modules (OMs) arranged on 4 strings (AMANDA-B4) was deployed at depths
between 1.5 and 2 km. In this paper we describe the design and performance of
the AMANDA-B4 prototype, based on data collected between February and November
1996. Monte Carlo simulations of the detector response to down-going
atmospheric muon tracks show that the global behavior of the detector is
understood. We describe the data analysis method and present first results on
atmospheric muon reconstruction and separation of neutrino candidates. The
AMANDA array was upgraded with 216 OMs on 6 new strings in 1996/97
(AMANDA-B10), and 122 additional OMs on 3 strings in 1997/98.Comment: 36 pages, 23 figures, submitted to Astroparticle Physic
Limits to the muon flux from WIMP annihilation in the center of the Earth with the AMANDA detector
A search for nearly vertical up-going muon-neutrinos from neutralino
annihilations in the center of the Earth has been performed with the AMANDA-B10
neutrino detector. The data sample collected in 130.1 days of live-time in
1997, ~10^9 events, has been analyzed for this search. No excess over the
expected atmospheric neutrino background is oberved. An upper limit at 90%
confidence level on the annihilation rate of neutralinos in the center of the
Earth is obtained as a function of the neutralino mass in the range 100
GeV-5000 GeV, as well as the corresponding muon flux limit.Comment: 14 pages, 11 figures. Version accepted for publication in Physical
Review
UV and optical light transmission properties in deep ice at the South Pole
Both absorption and scattering of light at wavelengths 410 to 610 nanometers were measured in the South Pole ice at depths 0.8 to 1 kilometer with the laser calibration system of the Antarctic Muon And Neutrino Detector Array (AMANDA). At the shortest wavelengths the absorption lengths exceeded 200 meters—an order of magnitude longer than has been reported for laboratory ice. The absorption shows a strong wavelength dependence while the scattering length is found to be independent of the wavelength, consistent with the hypothesis of a residual density of air bubbles in the ice. The observed linear decrease of the inverse scattering length with depth is compatible with an earlier measurement by the AMANDA collaboration (at ∼515 nanometers)
Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients
Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8 </=16, 16-24, and >24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients
CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells
Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5−/− BBDP rats. We then discovered that ER stress-induced apoptotic signaling through C/EBP-homologous protein (CHOP) occurs in Gimap5−/− T cells. Knockdown of CHOP by siRNA protected Gimap5−/− T cells from ER stress-induced apoptosis, thereby identifying a role for this cellular pathway in the T cell lymphopenia of the BBDP rat. These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells
Changing pattern of the detection of locoregional relapse in breast cancer: the Edinburgh experience
The guidelines for follow-up of breast cancer patients concentrate on the first 3–5 years, with either reduced frequency of visits or discharge after this. They also recommend mammography, but no evidence exists to inform frequency. We analyse treatable relapses in our unit from 1312 patients with early stage breast cancer treated by breast conserving surgery (BCS) and postoperative radiotherapy between 1991 and 1998 to assess appropriateness of the guidelines. A total of 110 treatable relapses were analysed. Treatable relapse developed at 1–1.5% per year throughout follow-up. Forty-eight relapses were in ipsilateral breast, 25 ipsilateral axilla, 35 contralateral breast, 2 both breasts simultaneously. Thirty-seven relapses (33.5%) were symptomatic, 56 (51%) mammographically detected, 15 (13.5%) clinically detected, 2 (2%) diagnosed incidentally. Mammography detected 5.37 relapses per 1000 mammograms. Patients with symptomatic or mammographically detected ipsilateral breast relapse had significantly longer survival from original diagnosis (P=0.0002) and from recurrence (P=0.0014) compared with clinically detected. Treatable relapse occurs at a constant rate for at least 10 years. Clinical examination detects a minority (13.5%). Relapse diagnosed clinically is associated with poorer outcome. Long-term follow-up based on regular mammography is warranted for all patients treated by BCS
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