Observation of Efficient Lower Hybrid Current Drive at High Density in Diverted Plasmas on the Alcator C-Mod Tokamak.

Efficient lower hybrid current drive (LHCD) is demonstrated at densities up to n[over ¯]_{e}≈1.5×10^{20} m^{-3} in diverted plasmas on the Alcator C-Mod tokamak by operating at increased plasma current-and therefore reduced Greenwald density fraction. This density exceeds the nominal "LH density limit" at n[over ¯]_{e}≈1.0×10^{20} m^{-3} reported previously, above which an anomalous loss of current drive efficiency was observed. The recovery of current drive efficiency to a level consistent with engineering scalings is correlated with a reduction in density shoulders and turbulence levels in the far scrape-off layer. Concurrently, rf wave interaction with the edge and/or scrape-off-layer plasma is reduced, as indicated by a minimal broadening of the wave frequency spectrum measured at the plasma edge. These results have important implications for sustaining steady-state tokamak operation and indicate a pathway forward for implementing efficient LHCD in a reactor.

Explaining Cold-Pulse Dynamics in Tokamak Plasmas Using Local Turbulent Transport Models.

A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.

Fast Low-to-High Confinement Mode Bifurcation Dynamics in a Tokamak Edge Plasma Gyrokinetic Simulation.

Transport barrier formation and its relation to sheared flows in fluids and plasmas are of fundamental interest in various natural and laboratory observations and of critical importance in achieving an economical energy production in a magnetic fusion device. Here we report the first observation of an edge transport barrier formation event in an electrostatic gyrokinetic simulation carried out in a realistic diverted tokamak edge geometry under strong forcing by a high rate of heat deposition. The results show that turbulent Reynolds-stress-driven sheared E×B flows act in concert with neoclassical orbit loss to quench turbulent transport and form a transport barrier just inside the last closed magnetic flux surface.

Turbulence Nonlinearities Shed Light on Geometric Asymmetry in Tokamak Confinement Transitions.

A comprehensive study of fully frequency-resolved nonlinear kinetic energy transfer has been performed for the first time in a diverted tokamak, providing new insight into the parametric dependences of edge turbulence transitions. Measurements using gas puff imaging in the turbulent L-mode state illuminate the source of the long known but as yet unexplained "favorable-unfavorable" geometric asymmetry of the power threshold for transition to the turbulence-suppressed H mode. Results from the recently discovered I mode point to a competition between zonal flow (ZF) and geodesic-acoustic modes (GAM) for turbulent energy, while showing new evidence that the I-to-H transition is still dominated by ZFs. The availability of nonlinear drive for the GAM against net heat flux through the edge corresponds very well to empirical scalings found experimentally for accessing the I mode.

Physics design of the in-vessel collection optics for the ITER electron cyclotron emission diagnostic.

Measurement of the electron cyclotron emission (ECE) is one of the primary diagnostics for electron temperature in ITER. In-vessel, in-vacuum, and quasi-optical antennas capture sufficient ECE to achieve large signal to noise with microsecond temporal resolution and high spatial resolution while maintaining polarization fidelity. Two similar systems are required. One views the plasma radially. The other is an oblique view. Both views can be used to measure the electron temperature, while the oblique is also sensitive to non-thermal distortion in the bulk electron distribution. The in-vacuum optics for both systems are subject to degradation as they have a direct view of the ITER plasma and will not be accessible for cleaning or replacement for extended periods. Blackbody radiation sources are provided for in situ calibration.

Temperature gradient scale length measurement: A high accuracy application of electron cyclotron emission without calibration.

Calibration is a crucial procedure in electron temperature (Te) inference from a typical electron cyclotron emission (ECE) diagnostic on tokamaks. Although the calibration provides an important multiplying factor for an individual ECE channel, the parameter ΔTe/Te is independent of any calibration. Since an ECE channel measures the cyclotron emission for a particular flux surface, a non-perturbing change in toroidal magnetic field changes the view of that channel. Hence the calibration-free parameter is a measure of Te gradient. BT-jog technique is presented here which employs the parameter and the raw ECE signals for direct measurement of electron temperature gradient scale length.

Effects of magnetic shear on toroidal rotation in tokamak plasmas with lower hybrid current drive.

Application of lower hybrid (LH) current drive in tokamak plasmas can induce both co- and countercurrent directed changes in toroidal rotation, depending on the core q profile. For discharges with q(0) <1, rotation increments in the countercurrent direction are observed. If the LH-driven current is sufficient to suppress sawteeth and increase q(0) above unity, the core toroidal rotation change is in the cocurrent direction. This change in sign of the rotation increment is consistent with a change in sign of the residual stress (the divergence of which constitutes an intrinsic torque that drives the flow) through its dependence on magnetic shear.

Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.

Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit-granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and ≥ 10 p.p.m. (48%, P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure-response trends were detected (P(trend)=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens.

Edge temperature gradient as intrinsic rotation drive in Alcator C-Mod tokamak plasmas.

Intrinsic rotation has been observed in I-mode plasmas from the C-Mod tokamak, and is found to be similar to that in H mode, both in its edge origin and in the scaling with global pressure. Since both plasmas have similar edge ∇T, but completely different edge ∇n, it may be concluded that the drive of the intrinsic rotation is the edge ∇T rather than ∇P. Evidence suggests that the connection between gradients and rotation is the residual stress, and a scaling for the rotation from conversion of free energy to macroscopic flow is calculated.

Estimating the potential impacts of intervention from observational data: methods for estimating causal attributable risk in a cross-sectional analysis of depressive symptoms in Latin America.

BACKGROUND: The field of epidemiology struggles both with enhancing causal inference in observational studies and providing useful information for policy makers and public health workers focusing on interventions. Population intervention models, analogous to population attributable fractions, estimate the causal impact of interventions in a population, and are one option for understanding the relative importance of various risk factors. With population intervention parameters, risk factors are effectively standardised, allowing one to compare their values directly and determine which potential intervention may have the greatest impact on the outcome. METHODS: The difference between total effects and population intervention parameters was examined using naïve, G-computation and inverse probability of treatment weighting approaches. The differences between these parameters and the intuitions they provide were explored using data from a 2003 cross-sectional study in rural Mexico. RESULTS: The assumptions, specific analytic steps, limitations and interpretations of the total effects and population intervention parameters are discussed, and code is provided in Stata. CONCLUSION: Population intervention parameters are a valuable and straightforward approach in epidemiological studies for making causal inference from the data while also supplying information that is relevant for researchers, public health practitioners and policy makers.

Observation of ion-cyclotron-frequency mode-conversion flow drive in tokamak plasmas.

Strong toroidal flow (Vphi) and poloidal flow (Vtheta) have been observed in D-3He plasmas with ion cyclotron range of frequencies (ICRF) mode-conversion (MC) heating on the Alcator C-Mod tokamak. The toroidal flow scales with the rf power Prf (up to 30 km/s per MW), and is significantly larger than that in ICRF minority heated plasmas at the same rf power or stored energy. The central Vphi responds to Prf faster than the outer regions, and the Vphi(r) profile is broadly peaked for r/a < or =0.5. Localized (0.3 < or = r/a < or =0.5) Vtheta appears when Prf > or =1.5 MW and increases with power (up to 0.7 km/s per MW). The experimental evidence together with numerical wave modeling suggests a local flow drive source due to the interaction between the MC ion cyclotron wave and 3He ions.

A matched, case-control study of the association between Schistosoma japonicum and liver and colon cancers, in rural China.

A study of liver and colon cancers and their association with a previous diagnosis of schistosomiasis was performed in rural Sichuan, China. The data analysed came from 127 liver-cancer and 142 colon-cancer patients, each matched, by age, gender, hospital and township, with one or two controls. The cancer cases were identified from the hospital records of three Sichuan counties (all of which have some level of endemic schistosomiasis japonicum): Meishan (66 liver and 54 colon cases), Pujiang (16 liver and 22 colon cases) and Xichang (45 liver and 66 colon cases). Each control was selected using the hospital records for the same year the matched case of cancer was diagnosed, when the control had been found to have an illness other than cancer. Previous schistosomal infection was determined by examining the medical records at the county hospitals, searching the records at the local schistosomiasis-control stations or health-surveillance units, and, when no written record could be found, by interviews with the subjects or their relatives. Given the extremely strong association between hepatitis and liver cancer in China, only data from hepatitis-negative pairs were used in the analyses. Previous schistosomal infection was found to be significantly associated with both liver cancer (odds ratio = 3.7; 95% confidence interval = 1.0-13) and colon cancer (odds ratio = 3.3; 95% confidence interval = 1.8-6.1). The results indicate a fraction of disease attributable to schistosomiasis of 24% for colon cancer, and (among the hepatitis-negative population) one of 27% for liver cancer.

Surgeon-controlled ultrasound-guided core biopsies in the breast--a prospective study and a new use for surgeons in the clinic.

AIMS: This study was to assess the accuracy of a surgeon performing ultrasound-guided core biopsies of the breast. METHODS: A prospective audit was carried out of 555 patients who underwent an ultrasound-guided core biopsy for a discrete solid mass [under 30 mm maximum diameter] by a single surgeon. The surgeon controlled the core biopsy needle and an ultrasonographer or radiologist provided the imaging with ultrasound. RESULTS: The accuracy of the surgeon in sampling the lesions [n = 555 core biopsies] was independent of the size of the lesion. This saved 272 patients having unnecessary surgery for a benign lesion. CONCLUSION: The practical involvement by the surgeon in breast ultrasound and performing core biopsies has reduced pressure on the breast radiologists, reduced the number of diagnostic surgical open biopsies and made the clinic more interesting for the surgeon. With increased surgical confidence in breast ultrasound, most small and impalpable cancers have pre-operative skin marking rather than X-ray wire localization prior to undergoing wide local excision. Trainee breast surgeons should be encouraged to learn breast ultrasound and core biopsies.

Relating amino acid sequence to phenotype: analysis of peptide-binding data.

We illustrate data analytic concerns that arise in the context of relating genotype, as represented by amino acid sequence, to phenotypes (outcomes). The present application examines whether peptides that bind to a particular major histocompatibility complex (MHC) class I molecule have characteristic amino acid sequences. However, the concerns identified and addressed are considerably more general. It is recognized that simple rules for predicting binding based solely on preferences for specific amino acids in certain (anchor) positions of the peptide's amino acid sequence are generally inadequate and that binding is potentially influenced by all sequence positions as well as between-position interactions. The desire to elucidate these more complex prediction rules has spawned various modeling attempts, the shortcomings of which provide motivation for the methods adopted here. Because of (i) this need to model between-position interactions, (ii) amino acids constituting a highly (20) multilevel unordered categorical covariate, and (iii) there frequently being numerous such covariates (i.e., positions) comprising the sequence, standard regression/classification techniques are problematic due to the proliferation of indicator variables required for encoding the sequence position covariates and attendant interactions. These difficulties have led to analyses based on (continuous) properties (e.g., molecular weights) of the amino acids. However, there is potential information loss in such an approach if the properties used are incomplete and/or do not capture the mechanism underlying association with the phenotype. Here we demonstrate that handling unordered categorical covariates with numerous levels and accompanying interactions can be done effectively using classification trees and recently devised bump-hunting methods. We further tackle the question of whether observed associations are attributable to amino acid properties as well as addressing the assessment and implications of between-position covariation.

Sensing scenes with silicon.

Scene analysis, the process of converting sensory information from peripheral receptors into a representation of objects in the external world, is central to our human experience of perception. Through our efforts to design systems for object recognition and for robot navigation, we have come to appreciate that a number of common themes apply across the sensory modalities of vision, audition, and olfaction; and many apply across species ranging from invertebrates to mammals. These themes include the need for adaptation in the periphery and trade-offs between selectivity for frequency or molecular structure with resolution in time or space. In addition, neural mechanisms involving coincidence detection are found in many different subsystems that appear to implement cross-correlation or autocorrelation computations.

Nonparametric survival estimation when death is reported with delay.

In disease registries there can be a delay between death of a subject and the reporting of this death to the data analyst. If researchers use the Kaplan-Meier estimator and implicitly assumed that subjects who have yet to have death reported are still alive, i.e. are censored at the time of analysis, the Kaplan-Meier estimator is typically inconsistent. Assuming censoring is independent of failure, we provide a simple estimator that is consistent and asymptotically efficient. We also provide estimates of the asymptotic variance of our estimator and simulations that demonstrate the favorable performance of these estimators. Finally, we demonstrate our methods by analyzing AIDS survival data. This analysis underscores the pitfalls of not accounting for delay when estimating the survival distribution and suggests a significant reduction in bias by using our estimator.

Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells.

Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34(+) cells). In this study, human cord blood, which is particularly rich in CD34(+) cells, was exposed to hydroquinone for 72 h in a medium that favored CD34(+) cell survival and growth. CD34(+) and CD34(-) cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34(+) cells were generally more susceptible to aneusomy induction by hydroquinone than CD34(-) cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34(+) cells (P(trend) < 0.001), whereas in CD34(-) cells only an increased level of monosomy 7 was detected (P(trend) = 0.002). Particularly striking effects of hydroquinone were observed in CD34(+) cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34(+) cells play a role in benzene-induced leukemogenesis.

Effects of acoustic trauma on acoustic enhancement of electrically evoked otoacoustic emissions.

Moderate acoustic trauma results in decreased cochlear sensitivity and frequency selectivity. This decrease is believed to be caused by damage to the cochlear amplifier that is associated with outer hair cells (OHCs) and their nonlinear electromechanical characteristics. A consequence of OHC nonlinearity is the acoustic enhancement effect, in which low-frequency electrically evoked otoacoustic emissions are enhanced by a simultaneous tone. The present study found that acoustic trauma reduced the acoustic enhancement effect and this reduction is correlated with the N1 threshold at the electrode site. This result is consistent with the theory that trauma affects the mechanoelectric transduction process, thus affecting cochlear mechanical nonlinearity. Acoustic trauma also reduced the cochlear microphonic in a way that suggests that the number of functioning tension-gated channels and the stiffness of the gating springs were decreased. In some cases, the electromechanical transduction process was also found to be affected by acoustic trauma.

Cerebrospinal fluid pharmacokinetics of cefpodoxime proxetil in piglets.

Cefpodoxime is an oral third-generation cephalosporin used for the treatment of acute upper-respiratory tract infections caused by susceptible bacteria in children. Although not indicated for the treatment of bacterial meningitis, it is used to treat other infections produced by organisms associated with meningitis and may obscure the result of cerebrospinal fluid (CSF) cultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSF. This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre-Camborough cross piglets (10-20 days old) received cefpodoxime proxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were collected over 24 hours for quantitation of cefpodoxime by HPLC. Pharmacokinetic analysis was performed on both plasma and CSF data. The plasma concentration versus time data for cefpodoxime were best characterized using a one-compartment model with first-order absorption. The mean (+/- SD) pharmacokinetic parameters for Cmax, tmax, and AUC0-infinity were 23.3 +/- 12.9 mg/L, 3.9 +/- 1.4 h, and 237 +/- 129 mg/L.h, respectively. CSF/plasma ratios for AUC0-infinity demonstrated a mean cefpodoxime penetration of approximately 5%. CSF penetration of cefpodoxime was evident following a single oral dose of cefpodoxime proxetil suspension. Despite the small percentage of total cefpodoxime dose distributing into the CSF, the resultant concentrations approached or exceeded the MIC90 for many bacterial pathogens considered susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical signs and symptoms consistent with meningitis and who have been previously treated with cefpodoxime.

Psychological stress in the workplace and menstrual function.

The relation between psychological stress at work and menstrual function was examined for 276 healthy, working, premenopausal women who participated in the California Women's Reproductive Health Study in 1990-1991. Subjects collected daily urine samples and completed a daily diary for an average of five menstrual cycles. Metabolites of estrogen and progesterone were measured in the urine, and computer algorithms were developed to characterize each cycle as ovulatory or anovulatory and to select a probable day of ovulation. A telephone interview collected information about psychological stress at work as well as other occupational, demographic, lifestyle, and environmental factors. Logistic regression was used to model stressful work and risk of anovulation (> or = 36 days without ovulating) and measures of within-woman cycle variability. Repeated measures analyses were performed on other menstrual cycle parameters. Stressful work (high demand in combination with low control) was not strongly related to an increased risk for anovulation or cycle variability or to any of the following cycle endpoints: short luteal phase (< or = 10 days), long follicular phase (> or = 24 days), long menses (> or = 8 days), or long cycle (> or = 36 days). However, women in stressful jobs had a more than doubled risk for short cycle length (< or = 24 days) compared with women not working in stressful jobs (adjusted odds ratio = 2.24, 95% confidence interval 1.09-4.59).