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The half-life of the superallowed Fermi β+ emitter 18Ne has been determined via two high-precision β counting experiments at TRIUMF's Isotope Separator and Accelerator facility. Using two different 4π continuous-flow gas-proportional counters, two independent measurements were made, yielding a weighted average of T1/2=1.66400+0.00057-0.00048 s, which is consistent with but approximately 2 times more precise than a previous high-precision measurement based on γ-ray counting. The present work achieves ±0.034% precision for the 18Ne half-life and will enable the inclusion of 18Ne among the set of precisely measured superallowed Fermi β-decay ft values once improved measurements are made for its Q value and superallowed branching ratio. As a test of systematic uncertainties, the half-life of 23Ne was measured and the world average has been improved, by a factor of 1.7, to 37.148±0.032 s. [ABSTRACT FROM AUTHOR]

The nuclear structure of 124Xe has been investigated via measurements of the β+/EC decay of 124Cs with the 8&#960γ-ray spectrometer at the TRIUMF-ISAC facility. The data collected have enabled branching ratio measurements of weak, low-energy transitions from highly excited states, and the 2+→0+ in-band transitions have been observed. Combining these results with those from a previous Coulomb excitation study, B(E2;23+3→02+)=78(13) W.u. and B(E2;24+→03+)=53(12) W.u. were determined. The 03+ state, in particular, is interpreted as the main fragment of the proton-pairing vibrational band identified in a previous 122Te(³He,n)124Xe measurement, and has quadrupole collectivity equal to, within uncertainty, that of the ground-state band. [ABSTRACT FROM AUTHOR]

At low stellar temperatures the energy release due to the CN cycle is regulated by its slowest reaction 14N(p,γ)15O, the rate of which strongly depends on the subthreshold resonance at Ec.m. = -504 keV, which corresponds to the 6.79 MeV state in 15O. By using the Doppler-shift attenuation method and the ³He(16O,α)15O reaction to populate the state, we obtained an upper limit on the lifetime of this state of τ < 1.8 fs [68.3% confidence level (C.L.)]. In addition we measured the lifetimes of the 6.18 and 6.86 MeV states to be τ < 2.5 and τ = 13.3-1.2+0.9 fs, respectively (68.3% C.L.), in good agreement with the literature. [ABSTRACT FROM AUTHOR]

A high-precision branching-ratio measurement for the superallowed β+ decay of 74Rb was performed at the TRIUMF Isotope Separator and Accelerator (ISAC) radioactive ion-beam facility. The scintillating electron-positron tagging array (SCEPTAR), composed of 10 thin plastic scintillators, was used to detect the emitted β particles; the 8Π spectrometer, an array of 20 Compton-suppressed HPGe detectors, was used for detecting γ rays that were emitted following Gamow-Teller and nonanalog Fermi β+ decays of 74Rb; and the Pentagonal Array of Conversion Electron Spectrometers (PACES), an array of 5 Si(Li) detectors, was employed for measuring β-delayed conversion electrons. Twenty-three excited states were identified in 74Kr following 8.241(4)×108 detected 74Rb β decays. A total of 58 γ-ray and electron transitions were placed in the decay scheme, allowing the superallowed branching ratio to be determined as B0=99.545(31)%. Combined with previous half-life and Q-value measurements, the superallowed branching ratio measured in this work leads to a superallowed ft value of 3082.8(65) s. Comparisons between this superallowed ft value and the world-average-corrected Ft value, as well as the nonanalog Fermi branching ratios determined in this work, provide guidance for theoretical models of the isospin-symmetry-breaking corrections in this mass region. [ABSTRACT FROM AUTHOR]

The half-life of the superallowed Fermi β+ emitter l4O has been determined via simultaneous direct β and γ counting experiments at TRIUMF's Isotope Separator and Accelerator (ISAC) facility. A γ-ray counting measurement was performed by detecting the 2312.6-keV γ rays emitted from an excited state of the daughter l4N following the implantation of samples at the center of the 8π γ-ray spectrometer, a spherical array of 20 high-purity germanium (HPGe) detectors. A simultaneous β counting experiment was performed using a fast plastic scintillator positioned behind the implantation site with a solid angle coverage of ~20%. The results, T1/2(β) = 70.610 ± 0.030 s and T1/2(γ) = 70.632 ± 0.094 s, form a consistent set and, together with eight previous measurements, establish anew average for the l40 half-life of T1/2 = 70.619 ± 0.011 s with a reduced X² of 0.99. [ABSTRACT FROM AUTHOR]

Based on results from a measurement of weak decay branches observed following the ß- decay of 94Y and on lifetime data from a study of 94Zr by inelastic neutron scattering, collective structure is deduced in the closed-subshell nucleus 94Zr. These results establish shape coexistence in 94Zr. The role of subshells for nuclear collectivity is suggested to be important. [ABSTRACT FROM AUTHOR]

A study of the ß+-electron capture decay of 110In into levels of 110Cd is combined with a reanalysis of data from a previous study of 110Cd with the (n, n'y) reaction with monoenergetic neutrons. The y y coincidences from the 110In decay leads to many new assignments of y rays observed in the (n, n'y) reaction, permitting the observation of weak low-energy transitions, and setting stringent upper limits on unobserved decay branches. The uncertainties on many of the lifetimes from the (n, n'y) reaction are significantly reduced, and limits are established for the lifetimes of levels too long for a direct measurement. The absence of enhanced transitions between the previously assigned phonon states and the deformed intruder states strongly suggests that mixing between the configurations is generally weak, refuting the strong-mixing scenario as an explanation of the decay pattern of the excited 0+ states in 110Cd. The decay pattern of the nonintruder states is suggestive of a y-soft rotor, or O(6) nucleus, rather than a vibrational, or U(5), pattern. The existence of a four-particle-six-hole proton excitation in 110Cd is also suggested. [ABSTRACT FROM AUTHOR]

The highly-efficient and segmented TIGRESS y-ray spectrometer at TRIUMF has been used to perform a reorientation-effect Coulomb-excitation study of the 2+ state at 3.368 MeV in l0Be. This is the first Coulomb-excitation measurement that enables one to obtain information on diagonal matrix elements for such a high-lying first excited state from y-ray data. With the availability of accurate lifetime data, a value of --0.110 ± 0.087 eb is determined for the 〈2+1||Ê2||2+1|〉 diagonal matrix element, which assuming the rotor model, leads to a negative spectroscopic quadrupole moment of Qs(2+1) = --0.083 ± 0.066 eb. This result is in agreement with both no-core shell-model calculations performed in this work with the CD-Bonn 2000 two-nucleon potential and large shell-model spaces, and Green's function Monte Carlo predictions with two- plus three-nucleon potentials. [ABSTRACT FROM AUTHOR]

A high-precision branching-ratio measurement for the superallowed ß+ emitter 26Alm was performed at the TRIUMF-ISAC radioactive ion beam facility. An upper limit of <12 ppm at 90% confidence level was found for the second forbidden yS+ decay of 26Alm to the 2 state at 1809 keV in 26Mg. An inclusive upper limit of 15 ppm at 90% confidence level was found when considering all possible nonanalog jö+/EC decay branches of 26 Alm, resulting in a superallowed branching ratio of 100.0000+0-0.0015 %. [ABSTRACT FROM AUTHOR]

A high precision lifetime measurement of the 21+ state in 94Sr was performed at TRIUMF's ISAC-II facility by coupling the recoil distance method implemented via the TIGRESS integrated plunger with unsafe Coulomb excitation in inverse kinematics. Due to limited statistics imposed by the use of a radioactive 94Sr beam, a likelihood ratio χ² method was derived and used to compare experimental data to Geant4 simulations. The B(E2; 21+ → 01+) value extracted from the lifetime measurement of 7.80-0.4+00.50 (stat.) ± 0.07 (sys.) ps is approximately 25% larger than previously reported while the relative error has been reduced by a factor of approximately 8. A baseline deformation has been established for Sr isotopes with N ≤ 58 which is a necessary condition for the quantum phase transition interpretation of the onset of deformation in this region. A comparison to existing theoretical models is presented. [ABSTRACT FROM AUTHOR]

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the β^{+}/electron-capture decay of ^{110,112}In and the β^{-} decay of ^{112}Ag, very weak decay branches from nonyrast states are observed. The transition rates determined from the measured branching ratios and level lifetimes obtained with the Doppler-shift attenuation method following inelastic neutron scattering reveal collective enhancements that are suggestive of a series of rotational bands. In ^{110}Cd, a γ band built on the shape-coexisting intruder configuration is suggested. For ^{112}Cd, the 2^{+} and 3^{+} intruder γ-band members are suggested, the 0&#95;{3}^{+} band is extended to spin 4^{+}, and the 0&#95;{4}^{+} band is identified. The results are interpreted using beyond-mean-field calculations employing the symmetry conserving configuration mixing method with the Gogny D1S energy density functional and with the suggestion that the Cd isotopes exhibit multiple shape coexistence.

The high incidence of injury in Rugby Union is well documented, particularly at elite levels of competition. This article describes the incidence and nature of all injuries sustained by elite Western Australian junior Rugby Union players during the 26 weeks up to and including the 1997 National Championship campaign. Informed consent was gained for each participant (n = 44) prior to completion of an extensive baseline questionnaire. Exposure and injury data were collected at each training session and game. The injury incidence rate over the 26 week period was 13.26/1000 player hours. Injury data were analysed by phase of play, position, severity and if occurred at games or training. The incidence of injury was significantly associated with the position played (chi2 = 67.49, p value = 0.008) and the phase of play in which the injury occurred (chi2 = 8.07, p value = 0.042). Tackling was the most dangerous phase of play (52% of injuries) and the most common site of injury was the lower limb (37%). Most injuries occurred during games (56%) and the flanker was the position most at risk of injury (12%). Further research is needed to identify the aetiology of injury at all levels of competition and to use these findings to develop effective injury prevention strategies in this sport. Position-specific risk factors should also be investigated, as should the mechanism of injury associated with tackling which is the phase of play in which significantly more injuries occur in rugby.

As we look at the literature from the 1970s and the present, it seems we have come full circle with regard to our understanding of objectives, competencies and outcomes. Our guidelines for writing them have become very complex. During the past few decades, health professions educators often have lost sight of the original intent and focused on the process of developing and writing objectives and competency statements. The process is now so complex that it is almost impossible to write a simple, understandable objective or competency statement. Perhaps that is why the "outcome" term was born. Outcome statements are really fairly broad competency statements. If we focus on the real purpose of objectives and make them simple, they become easier to evaluate. In the next article, we will explore methods for evaluating competence in the clinical setting.

Indomethacin has been shown clinically to inhibit growth of SCCHN (Panje, 1981). This inhibition appears to be due to augmentation of cellular immunity. The inhibitory effect of indomethacin may act by limiting tumor associated prostaglandin E2 production, thereby allowing return of costimulatory cytokines by antigen presenting cells. This would have the net result of relief from host unresponsiveness and promotion of B-cell and CTL differentiation, allowing the individual to mount an effective response. The enhancement of tumor infiltrating lymphocytes in SCCHN seen with indomethacin administration could presumably be further augmented when given in combination with cytokine therapy. Future investigation may allow the biochemical staging of an individuals' tumor to determine the optimal combination of cytokine therapy and prostaglandin inhibition through selective use of NSAID's. The effect of NSAID manipulation of prostaglandin and leukotriene metabolism on prevention of metastatic disease in SCCHN has yet to be studied. Given that a preselected, potentially responsive subset of immunocytes exists within the tumor tissue and lymph nodes, the development of the LAK phenomenon in TIL's and tumor draining lymph nodes from surgical specimens is a viable and exceedingly interesting area for future investigations in autologous LAK immunotherapy. The potential exists to harvest a preselected population of tumor infiltrating (Boscia, 1988) or tumor draining immunocytes (McKinnon, 1990). These can then potentially be returned to a state of antigen responsiveness with a combination of cytokine exposure (e.g. rIL-2) and systemic cytokine therapy. With subsequent inhibition of tumor associated prostaglandin synthesis by the systemic administration of prostaglandin synthesis inhibitors, it may be possible to successfully alter the host response to tumor.

Squamous cell carcinoma of the head and neck produces a prostaglandin, PGE2, a potent inhibitor of cellular immune responses. We tested the effects of prostaglandin synthetase inhibition on the infiltration of squamous cell carcinoma of the head and neck with host lymphocytes. Tumor tissue samples were obtained from six patients (age range, 51 to 72 years) who presented with squamous cell carcinoma of the head and neck before and after 14 days of treatment with indomethacin (50 mg administered orally three times a day). Tumor-infiltrating immune cells were assayed in frozen tissue samples by indirect immunofluorescence. An eightfold increase in CD2+ lymphocytes compared with pretreatment tissue was observed. The number of CD4 and CD8 lymphocytes increased similarly. CD57 lymphocytes increased 15-fold and CD11b cells increased 11-fold. No infiltrating B-cell populations were evident. Double-labeling studies revealed that the mononuclear cells were located outside blood vessel walls, indicating that they had infiltrated the tumor parenchyma. Our findings demonstrate that the administration of indomethacin is associated with the increased immune cell infiltration of squamous cell carcinoma of the head and neck. This suggests that inhibition of PGE2 synthesis as it occurs in the tumor and or systemically may contribute to the homing of mononuclear cells to the tumor. These data suggest a mechanism to account for the clinical response to indomethacin previously reported in squamous cell carcinoma.

Inflammatory mediators retained in middle ear effusion (MEE) during otitis media are important in influencing the clinical outcome of this disease. Interleukins, important immunomodulatory proteins, undoubtedly influence this inflammatory response. In our present study we analyzed 74 human middle ear effusion samples for interleukin-1 beta (IL-1 beta). Those effusions classified as purulent (POM) contained the highest levels, while those classified as serous (SOM) had the lowest. A statistically significant correlation between age and level of IL-1 beta was observed, namely, the younger group had higher levels of IL-1 beta than the older group in MOM and POM samples. The results of this study show that IL-1 beta is present in human middle ear effusion of otitis media and suggest that IL-1 beta may be an important mediator involved in the disease processes of otitis media.

Kinetics of 5-fluorouracil (FUra) and FUra metabolites in plasma and urine were investigated in 10 cancer patients following i.v. bolus administration of 500 mg/m2 FUra with 600 microCi of [6-3H]FUra. Biliary excretion was examined in two patients with external biliary catheters. Quantitation of unchanged drug and metabolites was assessed by a highly specific high-performance liquid chromatographic method. FUra plasma levels declined rapidly with an apparent elimination half-life of 12.9 +/- 7.3 min. Dihydrofluorouracil was detected within 5 min in most patients, demonstrating rapid catabolism and reached maximum peak levels of 23.7 +/- 9.9 microM at approximately 60 min. The apparent elimination half-life of dihydrofluorouracil (61.9 +/- 39.0 min) was consistently greater than that of the unchanged drug. The apparent elimination half-lives of the subsequent metabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine were prolonged with values of 238.9 +/- 175.4 min and 1976 +/- 358 min, respectively. Approximately 60-90% of the administered dose was excreted in urine within 24 h, primarily as alpha-fluoro-beta-alanine. Biliary excretion accounted for 2-3% of total administered radioactivity. The major fraction of this radioactivity eluted on high-performance liquid chromatography as a previously unrecognized FUra metabolite. Analysis of its structure is currently ongoing in our laboratory. In conclusion, this study provides the first comprehensive analysis of the formation and excretion of FUra metabolites in plasma, urine, and bile following i.v. bolus administration of FUra in humans.

Isolated rat hepatocytes in suspension were exposed to [3H]-5-fluorouracil for intervals over 2 h, following which the cells were removed from the media and sonicated, and the cytoplasm was sampled. High-performance liquid chromatography was used to separate 5-fluorouracil (FUra) from its known anabolites and catabolites, with subsequent quantitation of these metabolites by measurement of radioactivity. As the extracellular concentration of FUra was increased above 30 microM, the intracellular levels of FUra increased, with detection of a new peak of radioactivity distinct from any of the known anabolites or catabolites. This new metabolite, "G," increased in concentration as the extracellular concentration of FUra was raised above 1 mM. Inhibition of FUra catabolism by 2 mM thymine resulted in a further increase in intracellular FUra (approaching the extracellular FUra concentration) and was accompanied by a further increase in the intracellular concentration of "G," demonstrating that "G" was not formed via the catabolic pathway. The increase in intracellular FUra and "G" was not accompanied by an increase in intracellular anabolites, suggesting that "G" was formed via a novel metabolic pathway. "G" was retained within the hepatocytes, although it was not bound to intracellular macromolecules. "G" was converted to FUra in the presence of beta-D-glucuronidase; this reaction was inhibited with the addition of saccharo-1,4-beta-lactone, a specific inhibitor of the beta-D-glucuronidase. This data, together with evidence from hepatocyte homogenates in which formation of "G" was shown to be dependent on the concentration of uridine-5'-diphosphoglucuronic acid, demonstrates that "G" is a glucuronide of FUra. The formation of "G" suggests that FUra is metabolized via a previously unrecognized metabolic pathway.

The catabolism of 5-fluorouracil (FUra), which accounts for 90% of the elimination of this antimetabolite in vivo, has recently been characterized in freshly isolated rat hepatocytes in suspension using a highly specific high-performance liquid chromatographic methodology. The present study evaluates the effect of thymine and uracil, which are thought to be catabolized by the same enzymes as FUra, on the metabolism and transmembrane distribution of FUra in isolated rat hepatocytes. Following simulataneous exposure of cells for 5 min to 30 microM [6-3H]FUra and increasing concentrations of either thymine or uracil, dihydrofluorouracil (FUH2) levels decreased in a concentration-dependent manner, and the concentration determined for 50% inhibition of FUra catabolism was 8.0 +/- 0.3 (S.D.) and 67.8 +/- 15.6 microM for thymine and uracil, respectively. Analysis of intracellular and extracellular 3H from 1 min to 2 hr after simultaneous incubation of the hepatocytes with 30 microM FUra and thymine (or uracil) in a 1:7 molar ratio resulted in a decrease of intracellular and extracellular FUH2 and alpha-fluoro-beta-alanine (FBAL), while alpha-fluoro-beta-ureidopropionic acid (FUPA) was enhanced. Unmetabolized FUra (not detected in the absence of thymine or uracil) was detected intracellularly in the presence of thymine or uracil and was accompanied by the appearance of a novel metabolite, preliminarily identified as a glucuronide of the FUra base which reached intracellular levels of 44 +/- 9.76 and 27.45 +/- 1.35 microM in the presence of thymine or uracil, respectively, within 1 hr. This metabolite, which penetrates the cell membrane only slowly, accounted for approximately 60% of the intracellular 3H in the presence of 300 microM FUra and 2 mM thymine, whereas FUra catabolism was inhibited by more than 99% under these conditions. The formation of FUra anabolites was insignificant in the presence of thymine and uracil, and incorporation of FUra into RNA was not enhanced. The lack of anabolism of FUra in isolated hepatocytes exposed to either high initial concentrations of FUra or high intracellular FUra concentrations resulting from modulation (inhibition) of FUra catabolism is consistent with the clinical observation of minimal hepatotoxicity with FUra, despite exposure of the liver to high blood levels. These studies indicate that thymine is a more potent modulator of FUra catabolism in hepatocytes than is uracil. Further studies are needed to clarify the biological importance of the glucuronide of the base FUra which accumulates intracellularly as the concentration of FUra increases within the hepatocytes.