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Bupropion is an atypical antidepressant that increases long-term quit rates of tobacco smokers. A better understanding of the relation between nicotine and this first-line medication may provide insight into improving treatment. For all experiments, rats first had nicotine (0.4 mg base/kg) and saline session intermixed; intermittent access to sucrose only occurred on nicotine session. Nicotine in this protocol comes to differentially control "anticipatory" dipper entries. To more closely examine the overlap in the interoceptive stimulus effects of nicotine and bupropion, we assessed whether subsequent prolonged and repeated non-reinforced (extinction) sessions with the bupropion stimulus could weaken responding to nicotine (i.e., transfer of extinction). We also examined whether retraining the discrimination after initial extinction and then conducting extinction again (i.e., re-extinction) with bupropion would affect responding. We found that bupropion (20 and 30 mg/kg) fully substituted for the nicotine stimulus in repeated 20-min extinction sessions. The extent of substitution in extinction did not necessarily predict performance in the transfer test (e.g., nicotine responding unchanged after extinction with 20 mg/kg bupropion). Generalization of extinction back to nicotine was not seen with 20 mg/kg bupropion even after increasing the number of extinction session from 6 to 24. Finally, there was evidence that learning in the initial extinction phase was retained in the re-extinction phase for nicotine and bupropion. These findings indicate that learning involving the nicotine stimuli are complex and that assessment approach for stimulus similarity changes conclusions regarding substitution by bupropion. Further research will be needed to identify whether such differences may be related to different facets of nicotine dependence and/or its treatment.

In January and February 2009, a series of water samples were collected from streams on Byers Peninsula. These samples were analysed for major elements and δ18O to determine the role of lithology and landscape position on stream geochemistry, and to understand better the hydrology (i.e. residence time of water) of these systems. Precipitation chemistry is enriched in Na+, as are the streams located close to the coast. Streams originating from inland locations have much higher percentages of Ca2+. In contrast, Mg2+ varied little, though streams that are in greater contact with volcanic-derived soils have slightly higher concentrations. Anion percentages varied greatly between streams with SO42- ranging from 5% to 45% of the anion composition. Dissolved Si concentrations as high as 141 μM were observed. All these data suggest that active chemical weathering is occurring in this region. A time series over 13 days at one stream showed little variation in major element geochemistry. The δ18O of precipitation samples collected over this same period varied by ∼10‰ while the majority of stream samples varied less than ∼1.5‰. These data indicate that the stream waters represent mixtures of precipitation events, melting snow and water from the subsurface that had gained solutes through chemical weathering.

PURPOSE The aim of this randomized trial was to assess the potential therapeutic advantage of an intensive induction-sequential chemotherapy schedule (bleomycin, vincristine, cisplatin [BOP])/etoposide, ifosfamide, cisplatin, and bleomycin [VIP-B]), compared with a regimen based on bleomycin, etoposide, and cisplatin (BEP) (BEP/etoposide and cisplatin [EP]) for the treatment of patients with poor-prognosis metastatic nonseminomatous germ cell tumors (NSGCTs). PATIENTS AND METHODS Patients had one or more of the following: a retroperitoneal mass > or = 10 cm in diameter; mediastinal or supraclavicular mass > or = 5 cm in diameter; at least 20 lung metastases (any size); liver, bone, or brain metastases; and serum beta human chorionic gonadotropin (betaHCG) > or = 10,000 IU/L or alfa fetoprotein (AFP) > or = 1,000 IU/L. A total of 380 patients were accrued between May 1990 and June 1994 into this joint Medical Research Council (MRC)/European Organization for Research and Treatment of Cancer (EORTC) trial; of these, nine patients were deemed ineligible. RESULTS There was no significant difference between the two arms in the proportion of patients who achieved a complete response (CR) with chemotherapy alone, ie, 79 of 185 assessable patients (57%) with BEP/EP and 72 of 186 (54%) with BOP/VIP-B (P = 0.687). With a median follow-up of 3.1 years (maximum, 5.8), a total of 107 patients (28%) had progressive disease. There was no significant difference in time to first disease progression, or failure-free or overall survival between the two arms (P = 0.21, 0.101, and 0.190, respectively). The 1-year failure-free survival rates for BEP/EP and BOP/VIP-B were 60% (95% confidence interval [CI], 53% to 67%) and 53% (95% CI, 47% to 61%). Grade 3 or 4 myelosuppression, febrile neutropenia, and weight loss were more pronounced with BOP/VIP-B than with BEP/EP, and there were more toxic deaths with BOP/VIP-B than BEP/EP (18 [9%] v nine [5%]). CONCLUSION The intensive BOP/VIP-B therapy was associated with more toxicity, but there was no evidence of an improvement in response rate or survival compared with treatment with BEP/EP.

The dominant purple sulfur bacterium of laminated sediment ecosystems in temperate environments, Thiocapsa roseopersicina, was cultivated in sulfide-limited continuous cultures (D=0.03 h-1) subjected to various combined diel regimen of aeration and illumination in order to simulate environmental conditions in microbial mats. For comparison, cultures were grown under similar illumination regimens but continuously anoxic conditions. Bacteriochlorophyll a (BChla) and carotenoid synthesis was restricted to anoxic-dark periods and did not occur during oxic-light periods. An increase in the length of the oxic-light periods resulted in decreased pigment contents. However, phototrophic growth remained possible even at 20 h oxic-light/4 h anoxic-dark regimens. When anoxic conditions were maintained throughtout, BChla synthesis occurred both during light and dark periods. Glycogen was synthesized in the light and degraded in the dark. Calculations showed that degradation of 1/4–1/5 of the glycogen is sufficient to account for the BChla and carotenoid synthesis in the dark. The data showed that T. roseopersicina is very well adapted to cope with the combined oxygen and light regimes as they occur in microbial mats, which may explain the dominance of this bacterium in the purple layer of these sediment ecosystems.

We investigated the prognostic value of the serum half-life of human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP) during induction chemotherapy and the relative prognostic importance of initial marker concentrations and marker half-life. Marker half-lives were calculated using two abnormal values observed between day 8 and day 22 of the first chemotherapy cycle, Moreover, analyses were carried out using day 43 as the second measurement point. Treatment failure at any time was chosen as the end point. The relative prognostic influence of marker half-lives and initial marker concentrations was tested in univariate and multivariate analyses. Half-lives were considered to be prolonged ii > 3 days for HCG and > 6 days for AFP. In addition, we separated patients into those with half-lives > 6 days for HCG and those with half-lives > 10 days for AFP to examine whether these long half-lives were associated with a poor prognosis. A group of 669 patients treated with cisplatin combination chemotherapy was studied. Forty-two per cent of the patients had normal HCG and 37% had normal AFP at the start of chemotherapy. At day 22, HCG was still elevated in 138 patients and AFP in 211, At day 43, the numbers of these patients were 35 and 80 respectively. Based on the measurements obtained on day 8 and day 22, a half-life of HCG > 3 days or > 6 days and/or a half-life AFP > 6 days or > 10 days did not accurately predict treatment failure (P=0.413 and P=0.851, respectively; values obtained using tests for trend). However, initial marker concentrations of HCG and/or AFP greater than or equal to 1000 IU l(-1) were highly significant prognosticators for treatment failure (P=0.001 and P

We have investigated whether an alternating induction chemotherapy regimen of PVB/BEP is superior to BEP in patients with poor-prognosis testicular non-seminoma. A total of 234 eligible patients were randomised to receive an alternating schedule of PVB/BEP for a total of four cycles or four cycles of BEP. Poor prognosis was defined as any of the following: lymph node metastases larger than 5 cm, lung metastases more than four in number or larger than 2 cm, haematogenic spread outside the lungs, such as in liver and bone, human chorionic gonadotrophin > 10,000 IU l-1 or alphafetoprotein > 1000 IU l-1. The complete response (CR) rates to PVB/BEP and BEP were similar, 76% and 72% respectively (P = 0.58). In addition, there was no significant difference in relapse rate, disease-free and overall survival at an average follow-up of 6 years. The 5-year progression-free and survival rates in both treatment groups were approximately 80%. The PVB/BEP regime was more toxic with regard to bone marrow function; the frequencies of leucocytes below 1000 microliters-1, leucocytopenic fever and platelets below 25,000 microliters-1, throughout four cycles were 28% vs 5% (P < 0.001), 16% vs 5% (P = 0.006), and 10% vs 1% (P = 0.001) respectively. Neuropathy also occurred more often in the PVB/BEP arm: 47% vs 25% (P = 0.001). This study shows that an alternating regimen of PVB/BEP is not superior to BEP and that it is more myelo- and neurotoxic.

5137 Background: Our aim was to develop and validate clinically applicable predictive factors for a >30% PSA decline 3 months following chemotherapy initiation, and to assess the performance of a risk-group based classification in predicting PSA declines and overall survival (OS) in men receiving chemotherapy for mCRPC. Methods: In TAX327, 1006 men with mCRPC were randomized to receive docetaxel (D) in two schedules, or mitoxantrone (M), each with prednisone: 989 provided data on PSA decline at 3 months. Predictive factors for a >30% 3-month decline in PSA levels were identified using multivariate logistic regression in D treated men (n = 656) and validated in M treated men (n = 333). Risk factors were combined to form risk groups to predict PSA declines, OS, tumor, and pain responses. Prostate Cancer Working Group (PCWG2) disease states were evaluated for these outcomes in docetaxel treated men. Results: In multivariate analysis, four independent risk factors predicted for absence of >30% decline in 3-month PSA: significant baseline pain (OR 0.63 p = 0.02), visceral metastases (OR 0.66, p = 0.03), anemia (hemoglobin 30% PSA decline in 78, 66, and 58 percent of men (p < 0.001). In the validation M cohort, similar trends for PSA declines and OS were noted across risk groups (OS 22.5, 16.0, 11.8 mo, p < 0.001). PCWG2 subtypes (node only, bone metastatic, and visceral disease), were also highly prognostic and predictive but did not predict OS as well as the TAX327 risk groups (c-index 0.56). Conclusions: Risk groups have been identified and internally validated that predict PSA decline and OS in men with mCRPC. This classification may facilitate evaluation of new regimens of systemic therapy that warrant definitive testing in comparison to docetaxel and prednisone in phase III trials. Prospective validation of these risk groups is needed. [Table: see text]

The Heavy-Section Steel Technology (HSST) Program at the Oak Ridge National Laboratory under the sponsorship of the Nuclear Regulatory Commission is conducting analytical and experimental studies aimed at understanding the circumstances that would initiate the growth of an existing crack in a reactor pressure vessel (RPV) and the conditions leading to arrest of a propagating crack. Objectives of these studies are to determine (1) if the material will exhibit crack-arrest behavior when the driving force on a crack exceeds the ASME limit, (2) the relationship between K{sub Ia} and temperature, and (3) the interaction of fracture modes (arrest, stable crack growth, unstable crack growth, and tensile instability) when arrest occurs at high temperatures. In meeting these objectives, crack-arrest data are being developed over an expanded temperature range through tests involving large thermally shocked cylinders, pressurized thermally shocked vessels, and wide-plate specimens. The wide-plate specimens provide the opportunity for a significant number of data points to be obtained at relatively affordable costs. These tests are designed to provide fracture-toughness measurements approaching or above the onset of the Charpy upper-shelf regime in a rising toughness region and with an increasing driving force. This document discusses test methodology and results. 23 refs., 92 figs., 25 tabs.

Two 152-mm-thick wide-plate crack-arrest tests (WP-2 series) are discussed in this report. Each test used a 1 {times} 1 {times} 0.15 m thick single-edge-notch specimen (a/w = 0.2), fabricated from a low-upper-shelf base material, that was subjected to a linear thermal gradient along the plane of crack propagation. The tests were conducted at the National Institute of Standards and Technology and were designed to provide fracture-toughness measurements at temperatures approaching or above the onset of the Charpy upper-shelf regime in a rising toughness region and with an increasing driving force. Results obtained from these tests have produced crack-arrest toughness values well above the limit recognized by the current ASME guidelines (220 MPa {center dot} {radical}m) with arrests occurring at 44 to 102{degrees}C above the material DW{sub NDT} (60{degrees}C). The fracture data support (1) the use of fracture mechanics concepts to analyze cleavage run-arrest events, (2) the treatment of cleavage run-arrest and ductile fracture modes as separate events, and (3) the fact that cleavage arrest occurs above the ASME limit. 124 refs., 83 figs., 18 tabs.

5005 Background: The TAX-327 study compared 3 weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 patients (pts) with metastatic hormone resistant prostate cancer (mHRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, PSA and quality of life for D3 when compared with M (Tannock et al, NEJM 2004;351:1502–12). Here we present the updated survival analysis. Methods: Investigators were asked to provide date of death or last follow up for all patients alive in August 2003. Results: By December 2007 data on 276 additional deaths were obtained (total 833 deaths, see Table ). The survival benefit of D3 as compared with M has persisted with extended follow up while D1 continues to show no significant survival advantage. More patients (17.9% and 16.7%) survived =3 years in the D3 and D1 arms compared to M (13.7%). Similar trends in survival between treatment arms were seen for pts above and below 65 years of age, for those with and without pain at baseline, and for those with baseline PSA above and below median value of 115ng/ml. Conclusions: The present analysis confirms previous findings that survival is significantly longer with D3 than with M. Survival update is ongoing. [Table: see text] No significant financial relationships to disclose.

4557 Background: The TAX-327 study compared 3-weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 pts with mHRPC. Survival and symptom control were superior for treatment with D3+P as compared to M+P (Tannock et al, NEJM 2004;351;1502–12). Here we investigate QOL and its relation to pain, and effects of treatment on QOL in pts with minimal symptoms. Methods: Pts were assessable for pain response if Present Pain Intensity (PPI) ≥ 2 (range 0–5) or Analgesic Score (AS) ≥ 10. QOL was measured by the FACT-Prostate (FACT-P) self-report score (range 0–156, higher scores indicate better QOL). QOL response required a 16-point increase in FACT-P score maintained on 2 occasions; here deterioration of QOL was defined by a 16-point decrease from baseline in FACT-P score. Pts with minimal symptoms were defined at baseline by a FACT-P score > 128 or by PPI < 2 and AS < 10. Results: QOL was substantially impaired at baseline (FACT-P score ≤128) in 92% and 75% of pts who were and were not assessable for pain (p < 0.001). Correlation of FACT-P score with PPI and AS will be presented. QOL response and deterioration for all assessable pts, and for those with minimal symptoms are shown in the table (p-values compared with M+P). Time-dependent analysis of QOL and its relation to duration of treatment will be presented at the meeting. Conclusions: Most pts had impaired QOL at baseline regardless of pain. There was greater improvement in QOL following treatment with D+P compared to M+P for all pts and for pts with minimal symptoms. With the caveat that unequal withdrawal of pts might bias the data, there was greater probability of decline in QOL for pts receiving weekly docetaxel. [Table: see text] [Table: see text]

It is well known that the energy barrier for magnetization reversal, EB, varies quadratically with the magnetic field for the Stoner-Wohlfarth model. However, the enthalpy H (switching energy) required to reverse the magnetization is the sum of EB and the work Wf done by the Neel fluctuation field. The sum of these two terms gives an enthalpy of reversal. If the fluctuation field is uniaxial and parallel to the holding field, then the enthalpy barrier for switching is linear in the holding field. The linearity is consistent with certain experimental results. If the fluctuation field is anisotropic, then for the same size field, the probability of the particle’s switching will depend upon the direction of that field. The paper discusses the holding field variation of the energy barrier for different fluctuation field directions.

The difficulty in manufacturing Rockwell diamond indenters to the required geometric specifications has resulted in most commercially manufactured indenters to vary in shape from one to another. This difference in shape is thought to be a major contributor to the Rockwell C scale hardness measurement uncertainty. In this paper, a finite-element analysis (FEA) is used to simulate the Rockwell hardness measurement process. The influences of the indenter's geometry, including tip radius, cone angle, and form error on Rockwell hardness tests are analyzed by the FEA model, and further verified by experimental results. A new method is developed to directly input the Rockwell indenters' profiles into the FEA model for hardness performance prediction. The prediction results show good agreement with NIST experimental results.

Wide-plate crack-arrest tests are being performed at the National Bureau of Standards (Gaithersburg, MD) under the Heavy-Section Steel Technology (HSST) Program and are designed to provide fracture-toughness measurements at temperatures approaching or above the onset of the upper-shelf regime, in a rising toughness region and with increasing driving force. The test specimens are 1 × 1 × 0·1 m and possess a single-edge notch (crack) that initiates in cleavage propagation at low temperature and arrests in a region of increased fracture toughness. The toughness is achieved through a linear transverse temperature profile across the plate. Results obtained using a prototypical reactor pressure vessel steel (A533 grade B class 1 material) exhibit a significant increase in toughness at temperatures near and above the onset of Charpy upper shelf. Additionally, cleavage crack propagation and arrest at temperatures above the onset of Charpy upper shelf have been demonstrated.

Sixteen wide-plate crack-arrest tests have been completed, ten utilizing specimens fabricated from A533B Class 1 material and six fabricated from a low-upper-shelf base material. Each test utilized a single-edge notched specimen that was subjected to a linear thermal gradient along the plane of crack propagation. Test results exhibit an increase in crack-arrest toughness ( K Ia ) with temperature, with the rate of increase becoming greater as the temperature increases. When the wide-plate test results are compared with other large-specimen results, the data show a consistent trend in which the K Ia data extend above the limit provided in ASME Section XI.

The elastic energies of prismatic dislocation loops have been calculated as a continuous function of shape from equilateral triangle to hexagon. A smooth decrease in energy is found in this sequence; a relatively rapid change is associated with truncation of the triangle corners. The results are compared with previous calculations for other geometric shapes. The effect of a stacking fault in the loop plane is also considered.

The theory of disclinations contains the equation ∂iαij +ejmnθmn=0, where α and θ are the dislocation and disclination density tensors, respectively. This expression is interpreted to mean that dislocations can end on twist disclinations. A concrete example in a hexagonal crystal is discussed to illustrate this concept. It contains a 60° wedge disclination normal to the basal plane. By basic geometrical construction it is shown how a dislocation can be made to end on a jog in the wedge disclination. This jog is a small segment of twist disclination. Several ramifications of this concept are that disclinations can act as sources and sinks of dislocations, that dislocations change their Burgers vectors as they glide around disclinations, that a dislocation which crosses a disclination remains connected to it by a dislocation, that dislocations encircling a disclination must have a node, and that the local Burgers vector is not conserved on following a dislocation around a disclination.

In this paper we use straight‐line models of observed extrinsic nodes to estimate extrinsic stacking‐fault energies. Using isotropic elasticity theory and neglecting interactions, we find simple expressions for the energy in terms of the inscribed radii of the nodes. We apply the results to observed extended nodes in a silver—8 at.% tin alloy and find a ratio of extrinsic to intrinsic stacking‐fault energy of about 3.

A calculation is made on the segregation of solute atoms at stacking faults in f.c.c. crystals under equilibrium conditions. The expression given by Dorm relating the concentrations of solute atoms in the faulted and unfaulted regions is rederived. A new expression is given for the equilibrium width of the stacking fault in terms of the solute concentration, which can be interpreted in terms of the balance of forces on each partial dislocation. On the assumption that the stacking fault energy is exactly the difference in the free energy of the f.c.c. and h.c.p. structures of the same composition and temperature, it is shown that the f.c.c. and h.c.p. phase boundary concentrations of the alloy may be related to the concentration dependence of the stacking fault energy. A numerical example for a hypothetical alloy illustrates the various aspects of the theory.

Kroupa's theory of a continuous distribution of dislocation loops is extended to include disclination loops. The relation of the loop densities to the plastic strain and bend-twist are derived. This provides the connection with the theory of the continuous distribution of dislocations and disclinations. Mura has recently introduced the new concepts of “plastic distortion” and “plastic rotation”, and they are indentified in this paper as the dislocation-and disclination-loop density tensors. The significance of these quantities for a finite loop is discussed. Die Kroupasche Theorie einer kontinuierlichen Verteilung von Versetzungsschleifen wird auf Disklinationsschleifen erweitert. Die Beziehungen der Schleifendichten zur plastischen Verformung und Verdrillung werden abgeleitet. Dies liefert die Verbindung mit der Theorie der kontinuierlichen Verteilung von Versetzungen und Disklinationen. Kurzlich wurden von Mura neue Vorstellungen einer „plastischen Verzerrung” und „plastischen Drehung” eingefuhrt, diese werden in der Arbeit als Tensoren der Versetzungs- und Disklinationsschleifendichten identifiziert. Die Bedeutung dieser Grosen fur eine endliche Schleife wird diskutiert.

A regenerative mechanism is proposed which can lead to unlimited multiplication of disclinations. This mechanism consists of a glissile segment of a disclination pinned by two sessile ``jogs'', and therefore is similar to a Frank‐Read source for dislocations. It is also possible to have a U‐mill, Z‐mill, and L‐mill for disclination multiplication. It is further shown that a single source can give rise to disclinations of opposite signs (and this allows rotation in both directions of that part of the crystal above the source, relative to the part below), depending upon the direction in which the source operates.

The Heavy-Section Steel Technology (HSST) Program at the Oak Ridge National Laboratory, under the sponsorship of the US Nuclear Regulatory Commission, is conducting analytical and experimental studies aimed at understanding the circumstances that would initiate the growth of an existing crack in a reactor pressure vessel and the conditions that would lead to arrest of a propagating crack. HSST wide-plate crack-arrest tests are being performed at the National Institute of Standards and Technology (NIST), Gaithersburg, Maryland, in a 27-MN-capacity testing machine. This report contains results for two tests that used A 533 grade B class 1 material. Each test used a 1 x 1 x 0.15 m thick single-edge notched plate (a/w = 0.2) that was subjected to a linear thermal gradient along the plane of crack propagation. The thermal gradient was applied to the specimen by cooling the notched edge and heating the other edge. By varying the crack-tip temperature and transverse temperature profile, the initiation load and depth of crack propagation were changed from test to test. During each test, strain and temperature measurements were obtained as functions of position and time. Load, crack-opening displacement, and acoustic-emission data were also obtained as functions of time. 24 refs., 91more » figs., 12 tabs.« less

Two 102-mm-thick wide-plate crack-arrest tests (WP-CE series) are discussed in this report. Each test used a 1 {times} 1 {times} 0.1 m thick single-edge notched specimen (a/w = 0.2) fabricated from A 533 grade B class 1 steel that was subjected to a linear thermal gradient along the plane of crack propagation. The tests were conducted at the National Institute of Standards and Technology and were designed to provide fracture-toughness measurements at temperatures approaching or above the onset of the Charpy upper-shelf regime in a rising toughness region and with an increasing driving force. Results obtained from these tests have produced crack-arrest toughness values well above the limit recognized by the current ASME guidelines (220 MPa{center dot}{radical}m) with arrests occurring at 58 to 95{degree}C above the material RT{sub NDT} ({minus}35{degree}C). The fracture data support (1) the use of fracture mechanics concepts to analyze cleavage run-arrest events, (2) the treatment of cleavage run-arrest and ductile fracture modes as separate events, and (3) the fact that cleavage arrest occurs above the ASME limit. 47 refs., 87 figs., 13 tabs.