Clinicopathologic predictors of lymph node metastasis in breast cancer patients according to molecular subtype.

PURPOSE: We present a large institutional study to determine factors predictive of axillary lymph node (LN) metastasis in breast cancer according to molecular subtype. METHODS: We conducted a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2009 through December 2013. Clinicopathologic characteristics were correlated with lymph node status and outcome according to breast cancer molecular subtyping. RESULTS: LN metastases were detected in 464 (32.1%) of 1444 women with breast cancer. By multivariate analysis, independent factors predictive of LN involvement were: for the luminal A subtype (n=776): tumour size: OR=1.05 [95% CI: 1.03-1.07] P<0.0001; lymphovascular invasion: OR=3.06 [95% CI: 1.80-5.20] P<0.0001 and tumour grade: OR=1.65 [95% CI: 1.07-2.58] P=0.026. For luminal B subtype (n=441): age: OR=0.97 [95% CI: 0.95-0.99] P=0.004; tumour size: OR=1.03 [95% CI: 1.01-1.05] P=0.002; lymphovascular invasion: OR=3.21 [95% CI: 1.92-5.44] P<0.0001; inflammatory breast cancer: OR=12.36 [95% CI: 2.18-243.3] P=0.019. For the HER2 subtype (n=72): lymphovascular invasion: OR=7.87 [95% CI: 2.10-35.2] P=0.003. For the triple negative subtype (n=155): parity: OR=1.53 [95% CI: 1.10-2.25] P=0.02; tumour size: OR=1.03 [95% CI: 1.01-1.05] P=0.002 and lymphovascular invasion: OR=7.13 [95% CI: 2.46-22.8] P=0.00048. CONCLUSION: This retrospective study provides valuable insight into LN involvement of patients with primary breast cancer according to molecular subtyping.

[Outcomes of patients with breast cancer in function of their body mass index]. / Indice de masse corporelle et facteurs pronostiques du cancer du sein.

OBJECTIVE: The aim of this study was to evaluate outcomes of patients with breast cancer in function of the body mass index (BMI). METHODS: The study cohort consisted of consecutive women undergoing surgery for breast cancer in our institution between January 2009, and September 2013. Individual records of all patients were reviewed and analyzed. Patient BMI was categorized as underweight, normal, overweight and obese. RESULTS: A total of 1599 patients were evaluated. Patients were followed for one to 265months with a mean of 36.4months. The number of patients in each of the BMI categories was 66, 779, 463 and 291 for underweight, normal, overweight and obese women respectively. Women with higher BMI were more frequently affected by hypertension (18, 21, 35 and 47% respectively, P<0.0001) and diabetes (3, 2, 7 and 7% respectively, P<0.0001). Obese women had more frequently an inflammatory presentation (P=0.006), larger tumour size (P=0.038) and axillary lymph node involvement (P=0.03) with much more positive lymph nodes (P=0.02). Patients had the same protocols of treatment (surgery and adjuvant treatment). There was no statistically significant difference in overall 5-years survival between groups (P=0.30). CONCLUSIONS: Our study demonstrate a more aggressive clinical and histological presentation for obese women with breast cancer.

Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.

The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.

[Orbital infections in children: clinical signs, imaging, and treatment]. / Infections orbitaires de l'enfant : clinique, imagerie et traitement.

Orbital infections are rare in children. The more posterior the abscess has spread, the more serious it is, with potential intracranial complications. The main etiology is sinusitis, whose location depends on age. The diagnosis is based on clinical examination and CT or MRI. Intravenous antibiotics alone or associated with surgical drainage (for children older than 9 years or those with complications) are performed. Orbital infections in children require good collaboration between ophthalmologists, otolaryngologist, and pediatricians.

Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance.

Insulin resistance contributes to a number of metabolic disorders, including type II diabetes, hypertension, and atherosclerosis. Cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and hormones, such as growth hormone, are known to cause insulin resistance, but the mechanisms by which they inhibit the cellular response to insulin have not been elucidated. One mechanism by which these agents could cause insulin resistance is by inducing the expression of cellular proteins that inhibit insulin receptor (IR) signaling. Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling pathways, the expression of which is regulated by certain cytokines. SOCS proteins are therefore attractive candidates as mediators of cytokine-induced insulin resistance. We have found that SOCS-1 and SOCS-6 interact with the IR when expressed in human hepatoma cells (HepG2) or in rat hepatoma cells overexpressing the human IR. In SOCS-1-expressing cells, insulin treatment increases the extent of interaction with the IR, whereas in SOCS-6-expressing cells the association with the IR appears to require insulin treatment. SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro. These results suggest that SOCS proteins may be inhibitors of IR signaling and could mediate cytokine-induced insulin resistance and contribute to the pathogenesis of type II diabetes.

Spectral responsivity of various types of silicon photodiode at oblique incidence: comparison of measured and calculated values.

The spectral responsivity of several types of silicon photodiode at oblique incidence (approximately 45 degrees) is investigated. Both windowless diodes and diodes that incorporate quartz windows are considered. The spectral responsivities are measured directly for both parallel and perpendicular polarized radiation. For comparison, the responsivity at oblique incidence is also calculated from the normal-incidence measured responsivity in conjunction with the reflectance values at normal and oblique incidence calculated from thin-film theory by use of the measured oxide thicknesses of the diodes and published data on the refractive indices of silicon and fused silica. A technique, believed to be novel, is described for accurately measuring the oxide thicknesses of the diodes. A comparison of calculated and measured responsivity values shows that, when imperfect polarizers are used, it may be more accurate over a certain spectral range to calculate the responsivities at oblique incidence rather than to measure them directly. The additional uncertainty associated with the calculated responsivity values at oblique incidence, with respect to the original source data for normal incidence, is +/-1% over a wide spectral range.

Properties of Indium Antimonide Detectors for use as Transfer Standards for Detector Calibrations.

The properties of 4-mm-diameter and 7-mm-diameter liquid-nitrogen-cooled indium antimonide detectors were investigated to determine their suitability as transfer standards (i.e., reference detectors) for the detector calibration facility at the National Research Council of Canada. The spectral responsivity of the InSb detectors in the spectral range 1000-3000 nm was determined by atwo-step procedure involving the use of germanium transfer standardsand suitably characterized thermopiles. It is shown that thelong-term reproducibility of the InSb detector calibrations is approximately ?1%. The uniformity and linearity as a function of wavelength, as well as the background current noise and drift of thetwo detectors, are compared. It is shown that the 7-mm-diameter detector is clearly superior to the 4-mm one for use as a transfer standard. It is estimated that the overall accuracy of the calibrations of the two InSb detectors is ?2% in the range 1200-2800 nm.

T-ray tomography.

We demonstrate tomographic T-ray imaging, using the timing information present in terahertz (THz) pulses in a reflection geometry. THz pulses are reflected from refractive-index discontinuities inside an object, and the time delays of these pulses are used to determine the positions of the discontinuities along the propagation direction. In this fashion a tomographic image can be constructed.

chi((3)) squeezed vacuum generation without a Sagnac interferometer.

We show that an intense linearly polarized pulse propagating in a nonbirefringent fiber squeezes the perpendicularly polarized vacuum f luctuations through cross-phase modulation. Unlike the generation of squeezed vacuum through self-phase modulation, the mechanism discussed here does not require the use of a nonlinear Sagnac interferometer to separate the pump from the squeezed vacuum.

Development of improved electrical-substitution radiometers at the National Research Council of Canada.

We describe the development of a third generation of electrical-substitution radiometers (ESR's) at the National Research Council of Canada. The new ESR's follow the same general design as before, but incorporate improved thermopiles and electrical heating elements. The ESR's have a responsivity between 0.6 and 1.0 VW(-1), a time constant of approximately 2.0 s, a uniformity of 0.1% over a 6-mm-diameter region, and a noise level of approximately 6 nW. Performance characteristics of the new ESR's are discussed. It is shown that calibrations performed with these ESR's agree with those made with the previous generation of ESR's to better than 0.05%.

Raman-noise limit on squeezing in continuous-wave four-wave mixing.

The continuous-time quantum theory of self-phase modulation (SPM) in lossless, dispersionless, single-mode fiber requires a nonzero response time, to capture the classical SPM limit properly, and an accompanying Raman noise, to ensure commutator preservation. The continuous-wave, four-wave mixing limit of this theory is shown to harbor a Raman-noise limit on fiber-based squeezed-state generation.

Realization of a spectral irradiance scale in the near infrared at the National Research Council of Canada.

The measurements involved in the realization of a spectral irradiance scale in the near IR are described. Interference filters were used in conjunction with absolute radiometers to calibrate two different types of tungsten-halogen lamp at nine discrete wavelengths in the spectral range of 700-1600 nm. We discuss various aspects of these measurements: the apparatus used and alignment procedures, aging of the lamps and verification of their spectral characteristics, filter properties and measurements, some of the problems associated with the radiometric measurements, and data analysis. In particular it is shown that the interpolation formulas used to obtain spectral irradiance values at other wavelengths must be carefully chosen to avoid spurious errors. Two independent realizations were made; a comparison of the results obtained in the two cases indicated that some of the lamps had anomalous behavior. Finally it is shown that the new scale is in agreement with the scales realized by several other national laboratories within estimated uncertainties.

Oxidation of exogenous carbohydrate during prolonged exercise in fed and fasted conditions.

The oxidation of glucose and fructose ingested during moderate exercise performed on a cycle ergometer (120 min, 52% VO2max) was compared in ten young males fasted (n = 5) or fed (n = 5) before exercise. The subjects ingested randomly 1.33 g/kg body weight (approximately 96 +/- 9 g) of either enriched 13C-glucose (G), 13C-fructose (F), or water only (W); the solutions were evenly distributed over the exercise period. The fasted subjects began the three exercises with a lower blood glucose (P less than or equal to 0.05 for F only) and insulin (P less than or equal to 0.05) levels and a higher free fatty acid (FFA) concentration (P less than or equal to 0.05) than the fed ones. Throughout the exercise period, blood glucose level was maintained in fasted as well as in fed group for G and F ingestions, while it decreased (P less than or equal to 0.05 at the 100th min in fasted subjects) with water ingestion. Insulin level was similar in both fed and fasted conditions with F and W ingestions and lower than G trials for the fed subjects. For the three ingestions, FFA was lower (P less than or equal to 0.05) in the fasted than in the fed group over the exercise period. Over the 2-h period of exercise, a greater (P less than or equal to 0.05) amount of exogenous F was oxidized in the fasted (49 +/- 6 g) than in the fed (36 +/- 5 g) group, which represent 31% and 20% of the total carbohydrate energy supply, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffusers in silicon-photodiode radiometers.

The problems encountered when making radiometric measurements with silicon-photodiode radiometers not incorporating diffusers are discussed, with special attention given to the case where laser beams are involved. A diffuserless radiometer head design is presented which eliminates most of these problems. These problems can also be avoided by using a diffuser. A radiometer head incorporating a diffuser is described, and its properties are studied for three types of diffuser: flashed opal, type-2250 translucent Plexiglas, and a three-piece ground and etched quartz. Graphical data are given for the spatial uniformity, angular response variation, and spectral attenuation associated with radiometer heads incorporating these three types of diffuser. It is shown that, for a wide range of radiometric and photometric applications, the quartz diffuser is the most desirable, although its use results in a somewhat limited angular field of view.