Multiple Shape Coexistence in

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the ß^{+}/electron-capture decay of ^{110,112}In and the ß^{-} 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_{3}^{+} band is extended to spin 4^{+}, and the 0_{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.

Collective structure in 94Zr and subshell effects in shape coexistence.

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.

Coronary risk assessment among intermediate risk patients using a clinical and biomarker based algorithm developed and validated in two population cohorts.

BACKGROUND: Many coronary heart disease (CHD) events occur in individuals classified as intermediate risk by commonly used assessment tools. Over half the individuals presenting with a severe cardiac event, such as myocardial infarction (MI), have at most one risk factor as included in the widely used Framingham risk assessment. Individuals classified as intermediate risk, who are actually at high risk, may not receive guideline recommended treatments. A clinically useful method for accurately predicting 5-year CHD risk among intermediate risk patients remains an unmet medical need. OBJECTIVE: This study sought to develop a CHD Risk Assessment (CHDRA) model that improves 5-year risk stratification among intermediate risk individuals. METHODS: Assay panels for biomarkers associated with atherosclerosis biology (inflammation, angiogenesis, apoptosis, chemotaxis, etc.) were optimized for measuring baseline serum samples from 1084 initially CHD-free Marshfield Clinic Personalized Medicine Research Project (PMRP) individuals. A multivariable Cox regression model was fit using the most powerful risk predictors within the clinical and protein variables identified by repeated cross-validation. The resulting CHDRA algorithm was validated in a Multiple-Ethnic Study of Atherosclerosis (MESA) case-cohort sample. RESULTS: A CHDRA algorithm of age, sex, diabetes, and family history of MI, combined with serum levels of seven biomarkers (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, and sFas) yielded a clinical net reclassification index of 42.7% (p < 0.001) for MESA patients with a recalibrated Framingham 5-year intermediate risk level. Across all patients, the model predicted acute coronary events (hazard ratio = 2.17, p < 0.001), and remained an independent predictor after Framingham risk factor adjustments. LIMITATIONS: These include the slightly different event definition with the MESA samples and inability to include PMRP fatal CHD events. CONCLUSIONS: A novel risk score of serum protein levels plus clinical risk factors, developed and validated in independent cohorts, demonstrated clinical utility for assessing the true risk of CHD events in intermediate risk patients. Improved accuracy in cardiovascular risk classification could lead to improved preventive care and fewer deaths.

High-precision measurement of the 19Ne half-life and implications for right-handed weak currents.

We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262±0.007 s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.

High-precision half-life measurement for the superallowed ß+ emitter ²6Al(m).

A high-precision half-life measurement for the superallowed ß+ emitter 26Al(m) was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T 1/2 6346.54 ± 0.46(stat) ± 0.60 (syst) ms, consistent with, but 2.5 times more precise than, the previous world average. The 26Al(m) half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed ß decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for (26)Al(m), 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi ß-decay studies used to test the conserved vector current hypothesis and determine the V(ud) element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

Functional characterization of the GDEP promoter and three enhancer elements in retinoblastoma and prostate cell lines.

GDEP (gene differentially expressed in prostate cancer aka. PCAN1), a newly discovered gene with remarkable tissue specificity, is a promising candidate for regulatory analysis because it exhibits a high level of expression that is limited to two tissues, the retina and the prostate. As these two tissues have different origins and disparate functions it is likely that the regulatory mechanisms responsible for expression are not shared in their entirety. In addition, both the retina and prostate are prime targets for gene therapy. To date there have been no functional studies of the GDEP promoter. Therefore to understand tissue-specific expression of GDEP we constructed promoter expression constructs. To further characterize functional regulatory regions within the GDEP gene, we investigated potential regulatory components for tissue-specific expression in the 40 kb intron of this gene. We have identified a 1.5 kb prostate-specific promoter from the proximal region of the GDEP gene. A smaller 0.5 kb promoter exhibited minimal activity in the retinoblastoma cell line Y79, but not in the prostate cells tested. In addition we have investigated three enhancer elements located in the 40 kb intron of the GDEP gene. We identified two enhancer elements that increase reporter gene expression in prostate cell line LNCaP and one additional enhancer element that increases expression in the Y79 cell line approximately 8-fold making it a strong retinal-specific enhancer.

Incidence of injury in elite junior Rugby Union: a prospective descriptive study.

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.

Competency, objectives and outcomes.

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.

Tumor infiltrating lymphocytes in squamous cell carcinoma of the head and neck: mechanisms of enhancement using prostaglandin synthetase inhibitors.

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.

Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck.

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.

The levels of IL-1 beta in human middle ear effusions.

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.