Celecoxib decreases prostaglandin E\u3csub\u3e2\u3c/sub\u3e concentrations in nipple aspirate fluid from high risk postmenopausal women and women with breast cancer

Background Celecoxib inhibits PGE2 production in cancerous tissue. We previously reported that PGE2 levels in nipple aspirate fluid (NAF) and plasma were not decreased in women at increased breast cancer risk who received celecoxib 200 mg twice daily (bid). The endpoints of the current study were to determine if a short course of celecoxib 400 mg bid would decrease PGE2 levels in women 1) at increased breast cancer risk, and 2) with established breast cancer. Methods NAF and plasma samples were collected before, 2 weeks after taking celecoxib 400 mg bid, and two weeks after washout from 26 women who were at increased breast cancer risk. From 13 women with newly diagnosed breast cancer, NAF from the incident breast and plasma were collected before and on average 2 weeks after taking celecoxib. Additionally, in nine of the 13 women with breast cancer, NAF was collected from the contralateral breast. Results No consistent change in NAF or plasma PGE2 levels was noted in high risk premenopausal women. NAF PGE2 levels decreased after celecoxib administration in postmenopausal high risk women (p = 0.02), and in both the NAF (p = 0.02) and plasma (p = 0.03) of women with breast cancer. Conclusion Celecoxib 400 mg bid taken on average for 2 weeks significantly decreased NAF, but not plasma, PGE2 levels in postmenopausal high risk women, and decreased both NAF and plasma PGE2 levels in women with newly diagnosed breast cancer. PGE2 levels may predict celecoxib breast cancer prevention and treatment efficacy. Our observations are preliminary, and larger studies to confirm and extend these findings are warranted

Suppressing sensorimotor activity modulates the discrimination of auditory emotions but not speaker identity

Our ability to recognize the emotions of others is a crucial feature of human social cognition. Functional neuroimaging studies indicate that activity in sensorimotor cortices is evoked during the perception of emotion. In the visual domain, right somatosensory cortex activity has been shown to be critical for facial emotion recognition. However, the importance of sensorimotor representations in modalities outside of vision remains unknown. Here we use continuous theta-burst transcranial magnetic stimulation (cTBS) to investigate whether neural activity in the right postcentral gyrus (rPoG) and right lateral premotor cortex (rPM) is involved in nonverbal auditory emotion recognition. Three groups of participants completed same-different tasks on auditory stimuli, discriminating between the emotion expressed and the speakers' identities, before and following cTBS targeted at rPoG, rPM, or the vertex (control site). A task-selective deficit in auditory emotion discrimination was observed. Stimulation to rPoG and rPM resulted in a disruption of participants' abilities to discriminate emotion, but not identity, from vocal signals. These findings suggest that sensorimotor activity may be a modality-independent mechanism which aids emotion discrimination. Copyright © 2010 the authors

A Meta-Reinforcement Learning Algorithm for Causal Discovery

Uncovering the underlying causal structure of a phenomenon, domain or environment is of great scientific interest, not least because of the inferences that can be derived from such structures. Unfortunately though, given an environment, identifying its causal structure poses significant challenges. Amongst those are the need for costly interventions and the size of the space of possible structures that has to be searched. In this work, we propose a meta-reinforcement learning setup that addresses these challenges by learning a causal discovery algorithm, called Meta-Causal Discovery, or MCD. We model this algorithm as a policy that is trained on a set of environments with known causal structures to perform budgeted interventions. Simultaneously, the policy learns to maintain an estimate of the environment’s causal structure. The learned policy can then be used as a causal discovery algorithm to estimate the structure of environments in a matter of milliseconds. At test time, our algorithm performs well even in environments that induce previously unseen causal structures. We empirically show that MCD estimates good graphs compared to SOTA approaches on toy environments and thus constitutes a proof-of-concept of learning causal discovery algorithms

Celecoxib concentration predicts decrease in prostaglandin E\u3csub\u3e2\u3c/sub\u3e concentrations in nipple aspirate fluid from high risk women

BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib. METHODS: Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib. RESULTS: In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE2 levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE2 concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03). CONCLUSION: In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE2 production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE2 are of interest, in order to minimize the celecoxib dose required to have an effect

Air improvement recommendations for the San Francisco Bay area The Stanford-Ames NASA/asee SummerFaculty Systems Design workshop Final report

Air pollution monitoring and pollutant source surveillance system, and effective regulations and enforcement means for San Francisco Bay are

Temperature dependence of the band gap of 28Si:P at very low temperatures measured via time-resolved optical spectroscopy

We measure the temperature dependence of the indirect band gap of isotopically purified 28Si:P in the regime from 0.1 K to 3 K by high-resolution absorption spectroscopy of the donor bound exciton transition. The measurements increase the up-to-date precision of the temperature-dependent band gap change by more than one order of magnitude and reveal a T4 dependence which is about a factor of two less than observed in previous measurements. Such a T4 dependence is predicted by theory, but the absolute values differ between our experiment and the most up-to-date calculations by a factor of 30, corroborating that the electron-phonon interaction at low temperatures is still not correctly included into theory. What is more, the ability of such very high-precision band-gap measurements facilitates the use of time- and spatially resolved 28Si:P absorption as a contactless, local thermometer and electric field sensor with a demonstrated time resolution of milliseconds

Low Temperature Relaxation of Donor Bound Electron Spins in 28Si:P

We measure the spin-lattice relaxation of donor bound electrons in ultrapure, isotopically enriched, phosphorus-doped 28Si:P. The optical pump-probe experiments reveal at low temperatures extremely long spin relaxation times which exceed 20 h. The 28Si:P spin relaxation rate increases linearly with temperature in the regime below 1 K and shows a distinct transition to a T9 dependence which dominates the spin relaxation between 2 and 4 K at low magnetic fields. The T7 dependence reported for natural silicon is absent. At high magnetic fields, the spin relaxation is dominated by the magnetic field dependent single phonon spin relaxation process. This process is well documented for natural silicon at finite temperatures but the 28Si:P measurements validate additionally that the bosonic phonon distribution leads at very low temperatures to a deviation from the linear temperature dependence of Γ as predicted by theory

Low Temperature Relaxation of Donor Bound Electron Spins in Si 28: P

We measure the spin-lattice relaxation of donor bound electrons in ultrapure, isotopically enriched, phosphorus-doped Si28:P. The optical pump-probe experiments reveal at low temperatures extremely long spin relaxation times which exceed 20 h. The Si28:P spin relaxation rate increases linearly with temperature in the regime below 1 K and shows a distinct transition to a T9 dependence which dominates the spin relaxation between 2 and 4 K at low magnetic fields. The T7 dependence reported for natural silicon is absent. At high magnetic fields, the spin relaxation is dominated by the magnetic field dependent single phonon spin relaxation process. This process is well documented for natural silicon at finite temperatures but the Si28:P measurements validate additionally that the bosonic phonon distribution leads at very low temperatures to a deviation from the linear temperature dependence of Γ as predicted by theory

Breast cancer biomarkers predict weight loss after gastric bypass surgery

<p>Abstract</p> <p>Background</p> <p>Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n) levels of prostate specific antigen (PSA) were associated with obesity. Serum (s) levels of adiponectin are lower in women with higher body mass index (BMI) and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1) change in n- and s-adiponectin and nPSA after surgery and 2) if biomarker change is related to change in BMI. Samples (30-s, 28-n) and BMI were obtained from women 0, 3, 6 and 12 months after surgery.</p> <p>Findings</p> <p>There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline.</p> <p>Conclusions</p> <p>Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery.</p

Nipple aspirate cytology and pathologic parameters predict residual cancer and nodal involvement after excisional breast biopsy

We previously demonstrated that abnormal nipple aspirate fluid (NAF) cytology predicted residual breast cancer (RC) and tumour size after excisional biopsy (EB), although normal NAF cytology did not exclude RC. Tumour size correlates with the risk of lymph node (LN) metastases. LN metastases provide prognostic information allowing medical and radiation oncologists to determine the need for adjuvant therapy. We hypothesized that pathologic factors known after EB, combined with NAF cytology, would predict with a high degree of accuracy the presence of RC and LN spread. NAF cytology and pathologic parameters: tumour distance from biopsy margins, multifocal and multicentric disease, sub-type of ductal carcinoma in situ (DCIS) or invasive cancer (IC), grade of DCIS or IC, tumour and specimen size, tumour and biopsy cavity location, presence or absence of extensive DCIS, and biopsy scar distance from the nipple were evaluated bivariately and then by logistic regression (LR) for their association with RC and involved LN (≥ 1 (+) LN, useful to determine chemotherapy need, and ≥ 4 (+) LN, useful to determine radiation need to the chest and axilla). Data were analysed using NAF cytology alone, pathologic parameters alone, and NAF cytology and pathologic parameters combined. The combined LR model was superior in predicting residual cancer (94%) to LR models using NAF cytology (36%) or pathologic parameters (75%) alone. When only subjects with normal NAF cytology were evaluated by LR, the model was 92% sensitive in predicting RC. Tumour size and NAF cytology predicted which patients had ≥ 1 (+) LN, whereas tumour and specimen size predicted which patients had ≥ 4 (+) LN. We propose an alogorithm which, if confirmed in a larger study, may allow clinicians to be more selective in their recommendations of re-excision breast biopsy or mastectomy. © 2001 Cancer Research Campaign http://www.bjcancer.co