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Background: α-Tocopherol ether-linked acetic acid (α-TEA) is a promising agent for cancer prevention/therapy based on its antitumour actions in a variety of cancers.Methods: Human breast cancer cells, MCF-7 and HCC-1954, were used to study the effect of α-TEA using Annexin V/PI staining, western blot analyses, and siRNA knockdown techniques.Results: α-Tocopherol ether-linked acetic acid suppressed constitutively active basal levels of pAKT, pERK, pmTOR, and their downstream targets, as well as induced both cell types to undergo apoptosis. Phosphoinositide 3-kinase (PI3K) inhibitor wortmannin suppressed pAKT, pERK, pmTOR, and their downstream targets, indicating PI3K to be a common upstream mediator. In addition, α-TEA induced increased levels of pIRS-1 (Ser-307), a phosphorylation site correlated with insulin receptor substrate-1 (IRS-1) inactivation, and decreased levels of total IRS-1. Small interfering RNA (siRNA) knockdown of JNK blocked the impact of α-TEA on pIRS-1 and total IRS-1 and impeded its ability to downregulate the phosphorylated status of AKT, ERK, and mTOR. Combinations of α-TEA+MEK or mTOR inhibitor acted cooperatively to induce apoptosis and reduce basal levels of pERK and pmTOR. Importantly, inhibition of MEK and mTOR resulted in increased levels of pAKT and IRS-1, and α-TEA blocked them.Conclusions: Downregulation of IRS-1/PI3K pathways via JNK are critical for α-TEA and α-TEA+MEK or mTOR inhibitor-induced apoptosis in human MCF-7 and HCC-1954 breast cancer cells. [ABSTRACT FROM AUTHOR]

Theoretical methods in chemistry lead to algorithms for the computation of electronic energies and other properties of electronic wave functions that require large numbers of floating point operations and involve large data sets. Thus, computational chemists are very interested in using massively parallel computer systems and in particular the new petascale systems. In this paper we discuss a new programming paradigm that was developed at the Quantum Theory Project to construct electronic structure software that can scale to large numbers of cores of the order of 100,000 and beyond to solve problems in materials engineering relevant to the problems facing society today. [ABSTRACT FROM AUTHOR]

Kelli M Braun,1 Mark Sheridan,2 Erin Z Latif,1 Lexy Regush,3 Anet Maksymowicz,4 Laura Weins,5 Mohamed A Bedaiwy,6 Nerissa Tyson,5 Marilyn J Davidson,2 Barry H Sanders7 1Department of Obstetrics and Gynecology, Medical College of Georgia at Augusta University, Augusta, GA, USA; 2Department of Obstetrics and Gynecology, Saskatoon Obstetric and Gynecologic Consultants, 3Department of Obstetrics and Gynecology, Royal University Hospital, Saskatoon, 4Department of Obstetrics and Gynecology, Regina General Hospital, Regina, 5Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon City Hospital, Saskatoon, SK, 6Department of Obstetrics and Gynecology, British Columbia Women’s Hospital, Vancouver, 7Department of Obstetrics and Gynecology, Division of General Gynaecology and Obstetrics and Division of Gynaecologic Specialties, Vancouver General Hospital, Vancouver, BC, Canada Purpose: Successful adoption of a new surgical procedure varies among practicing surgeons, and skill acquisition depends on the surgeon’s innate ability, the complexity of the technique, and training. We report intraoperative and near-term postoperative outcomes from the Acessa procedure conducted by minimally invasive gynecologic surgeons new to Acessa, and report the surgeons’ experiences during the training period.Patients and methods: The study was designed as a postmarket, prospective, single-arm, multicenter analysis of operative and early postoperative outcomes after proctored surgical training with the Acessa device and procedure (laparoscopic ultrasound-guided radiofrequency volumetric thermal ablation of symptomatic fibroids) in premenopausal, menstruating women as conducted in community and university hospitals in the USA and Canada. Surgeons completed evaluation forms once they felt they could safely and comfortably conduct the operations.Results: Ten gynecologic surgeons without prior Acessa experience completed 40 Acessa procedures – all on an outpatient basis. Mean procedure time was 1.9±1.0 hours and was similar to that reported in the pivotal premarket study (2.1±1.0 hours). Two intraoperative complications occurred: a 1 cm uterine serosal laceration due to uterine manipulation and blood loss from both the probe insertion site and the lysis of uterine-omental adhesions. No postoperative complications or reinterventions for fibroid symptoms were reported. The surgeons completed the evaluation forms after two to five cases, and none found any factors affecting procedure efficiency to be inferior or needing improvement.Conclusion: Minimally invasive gynecologic surgeons new to Acessa can perform the procedure and provide acceptable outcomes after two to five proctored cases. Keywords: myoma, fibroid, leiomyoma, laparoscopic ultrasound, education, radiofrequency ablation

BACKGROUND AND PURPOSE: Clinical instructors (CIs) observe behavior to determine whether students have the skills assumed necessary for safe and effective delivery of physical therapy services. Studies have examined assumptions about necessary skills, but few studies have identified the types of student behaviors that are 'red flags' for CIs. This study examined the student behaviors that negatively affect students' clinical performance, which can alert CIs to inadequate performance. SUBJECTS: Twenty-eight female and 5 male CIs discussed the performance of 23 female and 17 male students who were anonymous. METHODS: Using questionnaires and semistructured interviews that were taped and transcribed, CIs described demographics and incidents of unsafe and ineffective physical therapy. After reading the transcripts, investigators identified and classified the behaviors into categories and checked their classification for reliability (kappa=.60-.75). RESULTS: Behaviors in 3 categories emerged as red flags for CIs: 1 cognitive category--inadequate knowledge and psychomotor skill (43% of 134 behaviors)--and 2 noncognitive categories--unprofessional behavior (29.1%) and poor communication (27.6%). The CIs noticed and valued noncognitive behaviors but addressed cognitive behaviors more often with students. Students who did not receive feedback about their performance were unlikely to change their behavior. The CIs used cognitive behaviors often as reasons to recommend negative outcomes. CONCLUSION AND DISCUSSION: Clinical instructors need to identify unacceptable cognitive and noncognitive behaviors as early as possible in clinical experiences. Evidence suggests that they should discuss their concerns with students and expect students to change. [ABSTRACT FROM AUTHOR]

Theoretical methods for empirical state determination of entangled two-level systems are analyzed in relation to information theory. We show that hidden variable theories would lead to a Shannon index of correlation between the entangled subsystems which is larger than that predicted by quantum mechanics. Canonical representations which have maximal correlations are treated by the use of Schmidt and Hilbert-Schmidt decomposition of the entangled states, including especially the Bohm singlet state and the GHZ entangled states. We show that quantum mechanics does not violate locality, but does violate realism. [ABSTRACT FROM AUTHOR]

In this study, we examined whether athletes, who typically replace only ≈50% of their fluid losses during moderate-duration endurance exercise, should attempt to replace their Na+ losses to maintain extracellular fluid volume. Six male cyclists performed three 90-min rides at 65% of peak O2 uptake in a 32°C environment and ingested either no fluid (NF), 1.2 l of water (W), or saline (S) containing 100 mmol of NaCl · l−1 to replace their electrolyte losses. Both W and S conditions decreased final heart rates by ≈10 betas · min−1 ( P < 0.005) and reduced falls in plasma volume (PV) by ≈4% ( P < 0.05). Maintenance of PV after 10 min in the W trial prevented further rises in plasma concentrations of Na+ [Na+], Cl− and protein but in the S and NF trials, plasma [Na+] continued to increase by ≈4 mEq · l−1. Differences in plasma [Na+] had little effect on the ≈2.4 l fluid, ≈120 mEq Na+ and ≈50 mEq K+ losses in sweat and urine in the three trials. The main effects of W and S were on body fluid shifts. During the NF trial, PV and interstitial fluid (ISF) and intracellular fluid (ICF) volumes decreased by ≈0.1, 1.2 and 1.0 l, respectively. In the W trial, the ≈1.2 l fluid and ≈120 mEq Na+ losses contracted the ISF volume, and in the S trial, ISF volume was maintained by the movement of water from the ICF. Since the W and S trials were equally effective in maintaining PV, Na+ ingestion may not be of much advantage to athletes who typically replace only ≈50% of their fluid losses during competitive endurance exercise. [ABSTRACT FROM AUTHOR]

Despite declines in mortality of cervical cancer, a sizable minority of women fail to obtain routine screening with the Papanicolaou smear and are at risk from this disease. Before implementing a long-term community-based intervention study to improve screening rates and reduce the stage of disease at diagnosis, a cervical cancer screening canvass of a defined population of poor, inner-city Baltimore residents was conducted between 1987 and 1989. A total of 4089 at-risk women were interviewed (81.3% response), of whom 95.5% reported ever having a Pap test, and 28% gave histories of inadequate recent screening. Reporting never having received a Pap test was associated with age, infrequent contact with the medical care system, and no recall of being advised how often to obtain Pap tests. Race was not a significant predictor. Logistic regression analysis yielded two important factors -- no recent physician visit or recall of periodicity recommendation. For current screening adequacy, age, medical care encounters and recall of physician advice were significant in bivariate analysis as well as in multivariate analysis: no racial differences were seen. The results demonstrate the key role played by primary health care providers and the power of physician advice in reinforcing the need to maintain routine screening examinations. Since most of the women interviewed had an encounter with the medical care system, 'missed opportunities' for early cancer detection continue to occur. [ABSTRACT FROM AUTHOR]