The Patient-Centered Dental Home: A Framework for Quality Measurement, Improvement, and Integration.

OBJECTIVE: This study completed the development of a standardized patient-centered dental home (PCDH) framework to align and integrate with the patient-centered medical home. This study identified measure concepts and specific measures and standards to complete the 4-level measurement framework to implement and evaluate a PCDH. This study built on prior model development, which identified the PCDH definition and characteristics and the components nested within those characteristics. METHODS: An environmental scan identified existing oral health care quality measure concepts, measures, and standards for rating by the project's National Advisory Committee (NAC). A modified Delphi process, adapted from the RAND appropriateness method, was used to obtain structured feedback from the NAC. NAC members rated measure concepts on importance and, subsequently, specific measures and standards on feasibility, validity, and actionability using a 1 to 9 rating scale. Criteria for model inclusion were based on median ratings and rating dispersion. Open-ended comments were elicited to inform model inclusion as well as identify additional concepts. RESULTS: We identified more than 500 existing oral health care measures and standards. A structured process was used to identify a subset that best aligned with a PCDH for rating by the NAC. Four Delphi rounds were completed, with 2 rounds to rate measure concepts and 2 rounds to rate measures and standards. NAC quantitative ratings and qualitative comments resulted in a total of 61 measure concepts and 47 measures and standards retained for inclusion in the framework. CONCLUSIONS: The NAC ratings of measure concepts, and specific measures and standards nested within those concepts, completed the 4-level PCDH measurement framework. The resulting framework allows for the development and implementation of core measure sets to identify and evaluate a PCDH, facilitating quality improvement and dental-medical integration. KNOWLEDGE TRANSFER STATEMENT: Clinicians, payers, health care systems, and policy makers can use the results of this study to guide and assess implementation of the various components of a patient-centered dental home and to support dental-medical integration.

Human and Environmental Dangers Posed by Ongoing Global Tropospheric Aerosolized Particulates for Weather Modification.

BACKGROUND: U.S. military perception of nuclear warfare led to countless unethical nuclear experiments performed on unsuspecting individuals without their informed consent. As evidenced here, subsequent perception of weather warfare has led to exposing millions of unsuspecting individuals to toxic coal fly ash with no public disclosure, no informed consent, and no health warnings. METHODS: Three methods were used: (1) comparison of eight elements analyzed in rainwater samples, thought to have leached from aerosolized coal fly ash, with corresponding coal fly ash laboratory leachate; (2) comparison of 14 elements analyzed in air filter dust with corresponding elements in coal fly ash; and (3) comparison of 23 elements analyzed in fibrous mesh found after snow melted with corresponding elements in coal fly ash. RESULTS: The rainwater element ratios show that the aerial particulate matter has essentially the same water-leach characteristics as coal fly ash. The air filter dust element ratios occur in the same range of compositions as coal fly ash, as do element ratios in fibrous mesh found on grass after snow melted. The fibrous mesh provides an inferred direct connection with the aerosolizing jet aircraft via coal fly ash association with the jet combustion environment. CONCLUSION: Strong evidence for the correctness of the hypothesis: coal fly ash is likely the aerosolized particulate emplaced in the troposphere for geoengineering, weather modification, and/or climate alteration purposes. The documented public health associations for ≤2.5 µm particulate pollution are also applicable to aerosolized coal fly ash. The ability of coal fly ash to release aluminum in a chemically mobile form upon exposure to water or body moisture has potentially grave human and environmental consequences over a broad spectrum, including implications for neurological diseases and biota debilitation. The ability of coal fly ash to release heavy metals and radioactive elements upon exposure to body moisture has potentially grave human health implications including cancer, cardiovascular disease, diabetes, respiratory diseases, reduced male fertility, and stroke. The fibrous mesh data admit the possibility of environmentally disastrous formation of methylmercury and ozone-depleting chlorinated-fluorinated hydrocarbons in jet exhaust. Geophysical implications include atmospheric warming and rainfall retardation.

Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health.

The widespread, intentional and increasingly frequent chemical emplacement in the troposphere has gone unidentified and unremarked in the scientific literature for years. The author presents evidence that toxic coal combustion fly ash is the most likely aerosolized particulate sprayed by tanker-jets for geoengineering, weather-modification and climate-modification purposes and describes some of the multifold consequences on public health. Two methods are employed: (1) Comparison of 8 elements analyzed in rainwater, leached from aerosolized particulates, with corresponding elements leached into water from coal fly ash in published laboratory experiments, and (2) Comparison of 14 elements analyzed in dust collected outdoors on a high-efficiency particulate air (HEPA) filter with corresponding elements analyzed in un-leached coal fly ash material. The results show: (1) the assemblage of elements in rainwater and in the corresponding experimental leachate are essentially identical. At a 99% confidence interval, they have identical means (T-test) and identical variances (F-test); and (2) the assemblage of elements in the HEPA dust and in the corresponding average un-leached coal fly ash are likewise essentially identical. The consequences on public health are profound, including exposure to a variety of toxic heavy metals, radioactive elements, and neurologically-implicated chemically mobile aluminum released by body moisture in situ after inhalation or through transdermal induction.

Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes.

Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80 % of human breast cancers. Its near-universal expression in breast cancer as well as its exquisite tissue specificity makes it an attractive target for a breast cancer prevention vaccine, and we recently initiated a phase 1 clinical trial of a MAM-A DNA vaccine. Previously, we have identified multiple MAM-A CD8 T cell epitopes using a reverse immunology candidate epitope approach based on predicted binding, but to date no attempt has been made to identify epitopes using an unbiased approach. In this study, we used human T cells primed in vitro with autologous dendritic cells expressing MAM-A to systematically identify MAM-A CD8 T cell epitopes. Using this unbiased approach, we identified three novel HLA-A2-restricted MAM-A epitopes. CD8 T cells specific for these epitopes are able to recognize and lyse human breast cancer cells in a MAM-A-specific, HLA-A2-dependent fashion. HLA-A2(+)/MAM-A(+) breast cancer patients have an increased prevalence of CD8 T cells specific for these novel MAM-A epitopes, and vaccination with a MAM-A DNA vaccine significantly increases the number of these CD8 T cells. The identification and translational validation of novel MAM-A epitopes has important implications for the ongoing clinical development of vaccine strategies targeting MAM-A. The novel MAM-A epitopes represent attractive targets for epitope-based vaccination strategies, and can also be used to monitor immune responses. Taken together these studies provide additional support for MAM-A as an important therapeutic target for the prevention and treatment of breast cancer.

Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study.

The feasibility of symptom-limited cardiopulmonary exercise testing (CPET) prior to allo-SCT was assessed in addition to the prognostic value of CPET-derived measures. CPET was performed prospectively on 21 patients with hematologic malignancies, with assessments of peak (for example, peak oxygen consumption, VO2peak) and submaximal (for example, ventilatory threshold (VT)) measures of cardiopulmonary function. No serious adverse events were observed during CPET procedures, with 95% of patients achieving criteria for a peak test. Mean VO2peak was 24.7±6.4 mL kg(-1 )min(-1) (range: 10.9-35.5), equivalent to 29%±17% below that of age-matched healthy controls. All patients proceeded with the conditioning regimen followed by allo-SCT. Median follow-up was 25 months. During this period, 11 (52.4%) patients died (n=6, relapsed disease; n=5, non-relapse mortality (NRM)); 9 patients (43%) developed pulmonary toxicity. In univariate analyses, both peak and submaximal markers of cardiopulmonary function were predictors of OS, pulmonary toxicity and NRM. For OS, the HR for VO2peak and VT were 0.89 (95% CI, 0.8-0.99, P=0.04) and 0.84 (95% CI, 0.71-0.98, P=0.03), respectively. In conclusion, CPET is safe and feasible prior to allo-SCT. Patients have marked impairments in cardiopulmonary function prior to allo-SCT. CPET-derived metrics may complement conventional measures to improve risk stratification.

Hematology and serum chemistry values of sooty mangabeys (Cercocebus atys): comparison with rhesus monkeys.

BACKGROUND: The sooty mangabey is a vulnerable West African species that naturally harbors simian immunodeficiency virus (SIV) without pathological symptoms. We present normative hematology and serum chemistry values for this species. METHODS: Hematology analytes from 136 females and 96 males and serum chemistry analytes from 57 females and 26 males were studied. RESULTS: Values of several analytes fell outside published reference ranges in the rhesus monkey, a laboratory standard for Old World primates. Erythrocyte-related parameters were higher in mangabeys than in rhesus monkeys, while platelet counts were lower. Mangabeys also had higher gamma-glutamyltransferase levels and lower urea nitrogen levels. Males had higher erythrocyte-associated values than females. Albumin, globulin, albumin/globulin ratio, calcium, and creatinine changed with age in patterns similar to those reported for the rhesus monkey. CONCLUSIONS: The unique blood profile of the mangabey should be taken into account in clinical and experimental studies of this species.

Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients.

BACKGROUND: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries. METHODS: We analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase II clinical trials evaluating bevacizumab regimens for recurrent glioblastoma. Of note, the five trials contained similar eligibility, treatment and assessment criteria, and achieved comparable outcome. RESULTS: The median overall survival (OS) and OS at 6 months for patients who continued bevacizumab therapy (n=55) were 5.9 months (95% confidence interval (CI): 4.4, 7.6) and 49.2% (95% CI: 35.2, 61.8), compared with 4.0 months (95% CI: 2.1, 5.4) and 29.5% (95% CI: 17.0, 43.2) for patients treated with a non-bevacizumab regimen (n=44; P=0.014). Bevacizumab continuation was an independent predictor of improved OS (hazard ratio=0.64; P=0.04). CONCLUSION: The results of our retrospective pooled analysis suggest that bevacizumab continuation beyond initial progression modestly improves survival compared with available non-bevacizumab therapy for recurrent glioblastoma patients require evaluation in an appropriately randomised, prospective trial.

Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).

The genomic response of the ipsilateral and contralateral cortex to stroke in aged rats.

Aged rats recover poorly after unilateral stroke, whereas young rats recover readily possibly with the help from the contralateral, healthy hemisphere. In this study we asked whether anomalous, age-related changes in the transcriptional activity in the brains of aged rats could be one underlying factor contributing to reduced functional recovery. We analysed gene expression in the periinfarct and contralateral areas of 3-month- and 18-month-old Sprague Dawley rats. Our experimental end-points were cDNA arrays containing genes related to hypoxia signalling, DNA damage and apoptosis, cellular response to injury, axonal damage and re-growth, cell lineage differentiation, dendritogenesis and neurogenesis. The major transcriptional events observed were: (i) Early up-regulation of DNA damage and down-regulation of anti-apoptosis-related genes in the periinfarct region of aged rats after stroke; (ii) Impaired neurogenesis in the periinfarct area, especially in aged rats; (iii) Impaired neurogenesis in the contralateral (unlesioned) hemisphere of both young and aged rats at all times after stroke and (iv) Marked up-regulation, in aged rats, of genes associated with inflammation and scar formation. These results were confirmed with quantitative real-time PCR. We conclude that reduced transcriptional activity in the healthy, contralateral hemisphere of aged rats in conjunction with an early up-regulation of DNA damage-related genes and pro-apoptotic genes and down-regulation of axono- and neurogenesis in the periinfarct area are likely to account for poor neurorehabilitation after stroke in old rats.

Phase II trial of irinotecan/gemcitabine as second-line therapy for relapsed and refractory small-cell lung cancer: Cancer and Leukemia Group B Study 39902.

BACKGROUND: This phase II study evaluated the efficacy and safety of the irinotecan/gemcitabine combination in patients with relapsed/refractory small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with measurable tumor who had received one previous chemotherapy or chemotherapy/radiation regimen were eligible. Gemcitabine 1000 mg/m(2) was administered i.v. over 30 min followed immediately by irinotecan 100 mg/m(2) i.v. over 90 min, both on days 1 and 8 every 21 days. Patients were stratified based on response to initial treatment [i.e. primary sensitive disease with progression >or=3 months (group A), or refractory disease (group B)]. RESULTS: Seventy-three patients were enrolled but one never received treatment and one ineligible patient did not have SCLC. Median patient ages of the remaining patients were 61 and 63 years in groups A (n = 35) and B (n = 36), respectively, with performance status of 0 or 1 in 85% of 71 patients. Primary grade 3/4 toxic effects in groups A versus B were neutropenia (36% versus 43%), thrombocytopenia (36% versus 26%), nausea (12% versus 11%), vomiting (0 versus 11%), diarrhea (12% versus 9%), and pulmonary (12% versus 12%). Two patients had fatal events including pneumonitis (n = 1) and acute respiratory distress syndrome (n = 1). Responses occurred in 11 group A [two complete responses and nine partial responses (PRs)] and four group B (all PRs) patients, for response rates of 31% [95% confidence interval (CI) 17%, 49%) and 11% (95% CI 3%, 26%), respectively. Median survival and progression-free survival times were 7.1 (95% CI 6, 10.5) versus 3.5 (95% CI 3.1, 5.7) months, and 3.1 (95% CI 1.6, 5.3) versus 1.6 (95% CI 1.4, 2.8) months for group A versus B. CONCLUSION: The irinotecan/gemcitabine combination is active and well tolerated as second-line therapy in SCLC patients. Additional studies are warranted as second-line therapy in patients who progressed 90 days or more after first-line therapy. However, the observed efficacy results in refractory SCLC patients indicate that this regimen should not be further explored in this population.

Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation.

Elevated intratumoral interstitial fluid pressure (IFP) and tumour hypoxia are independent predictive factors for poor survival and poor treatment response in cancer patients. However, the relationship between IFP and tumour hypoxia has not yet been clearly established. Preclinical studies have shown that lowering IFP improves treatment response to cytotoxic therapy. Interstitial fluid pressure can be reduced by inhibition of phosphorylated platelet-derived growth factor receptor-beta (p-PDGFR-beta), a tyrosine kinase receptor frequently overexpressed in cancer stroma, and/or by inhibition of VEGF, a growth factor commonly overexpressed in tumours overexpressing p-PDGFR-beta. We hypothesised that Imatinib, a specific PDGFR-beta inhibitor will, in addition to p-PDGFR-beta inhibition, downregulate VEGF, decrease IFP and improve tumour oxygenation. A549 human lung adenocarcinoma xenografts overexpressing PDGFR-beta were grown in nude mice. Tumour-bearing animals were randomised to control and treatment groups (Imatinib 50 mg kg(-1) via gavage for 4 days). Interstitial fluid pressure was measured in both groups before and after treatment. EF5, a hypoxia marker, was administered 3 h before being killed. Tumours were sectioned and stained for p-PDGFR-beta, VEGF and EF5 binding. Stained sections were viewed with a fluorescence microscope and image analysis was performed. Imatinib treatment resulted in significant reduction of p-PDGFR-beta, VEGF and IFP. Tumour oxygenation was also significantly improved. This study shows that p-PDGFR-beta-overexpressing tumours can be effectively treated with Imatinib to decrease tumour IFP. Importantly, this is the first study demonstrating that Imatinib treatment improves tumour oxygenation and downregulates tumour VEGF expression.

Age influences the expression of GAP-43 in the rat hippocampus following seizure.

BACKGROUND: Normal aging is associated with impairments in learning and memory and motor function. One viable hypothesis is that these changes reflect an age-related decrease in brain plasticity. OBJECTIVE: The aim of the present study was to identify age-related changes in the time course of expression of the axonal growth associated protein 43 (GAP-43) in a rat model of brain plasticity. METHODS: We examined by Northern blotting, in situ hybridization, and immunohistochemistry the effects of age on the time course of the expression GAP-43 following pentylenetetrazole-induced seizure in the hippocampus of 3-, 18-, and 28-month-old rats. RESULTS: In this model of brain plasticity, young rats displayed a decrease in GAP-43 mRNA levels in CA1, CA3, and polymorphic regions, lasting from 10 h to 3 days after seizure. This was followed by recovery, with peak expression between days 10 and 20. The baseline levels of GAP-43 mRNA decreased with age, especially in the CA3 region. Despite lower baseline levels, middle-aged rats showed the same pattern of upregulation of GAP-43 mRNA expression as the young animals. Old rats showed only minimal upregulation, however, and this occurred only in the polymorphic layer. The level GAP-43 protein itself was higher in old control rats than in the other two control groups, a condition that was transiently reversed by seizure activity. CONCLUSIONS: Middle-aged rats are still capable of a sustained, though diminished, response to seizure activity, while old rats lose this ability. Disruption of the temporal and anatomical coordination of expression of GAP-43 may contribute to the general decline in brain plasticity with age.

Executive function is less sensitive to estradiol than spatial memory: performance on an analog of the card sorting test in ovariectomized aged rhesus monkeys.

Functions supported by the frontal lobes are particularly sensitive to the detrimental effects of aging. Recent studies on postmenopausal women find that estrogen replacement therapy benefits performance on tasks dependent on the frontal lobes. To determine whether estrogen has a similar influence in a rhesus monkey model of menopause, we tested five aged, long-term ovariectomized rhesus monkeys in a modified version of the Wisconsin Card Sort test which had been adapted to the nonhuman primate. In this test, monkeys had to select 3-D objects based either on color (blue, red, yellow) or shape (block, tube, cup) and had to be able to switch their response as a function of reinforcement contingencies. The monkeys were treated with placebo and ethinyl estradiol (EE2, 450 ng/kg/day) in alternation with each successive test. Contrary to our hypothesis, estradiol treatment did not affect performance. Because previous studies in the same monkeys [Neurobiol. Aging 23 (2002) 589] had shown that EE2 improves performance on a spatial memory task dependent on the hippocampus, but not on another task dependent upon the frontal lobes (the delayed response), we conclude that executive processes may be less sensitive to the effects of estradiol than hippocampal-dependent tasks.

Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity.

BACKGROUND: Combined modality therapy (CMT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC); however, insufficient data are available regarding prognostic factors in this disease setting. PATIENTS AND METHODS: Six hundred and ninety-four patients included in five trials conducted by the Cancer and Leukemia Group B evaluating CMT in stage III NSCLC were included in this analysis. The primary objective was to identify factors that were predictors of survival and selected radiation-related toxicities using Cox regression models and logistic regression analysis. RESULTS: The Cox model shows that performance status (PS) 1 [hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.06-1.45; P=0.009] and thoracic radiation therapy (TRT) only (HR 1.58; 95% CI 1.22-2.05; P=0.001) predicted for poorer survival, while baseline hemoglobin >/=12 g/dl predicted for improved survival (HR 0.67; 95% CI 0.55-0.81; P 5% weight loss (OR 2.9; 95% CI 1.3-6.6; P=0.008) and patients receiving concurrent chemoradiation (OR 7.3; 95% CI 3.4-15.6; P=0.0001). CONCLUSIONS: Baseline hemoglobin and PS, as well as the use of CMT, have the greatest effect on survival in unresectable stage III NSCLC. The use of concurrent chemoradiation increases the risk of esophagitis, which remains the primary radiation-related toxicity.

Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC.

BACKGROUND: To evaluate the activity and tolerability of gemcitabine plus irinotecan or docetaxel as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients with chemotherapy-naïve stage IIIB or IV NSCLC were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8, plus either irinotecan 100 mg/m2 or docetaxel 40 mg/m2 on days 1 and 8. Treatment was administered every 3 weeks. RESULTS: Of the 80 enrolled patients with stage IIIB or IV NSCLC, 78 were evaluable for activity and safety. Overall response rates, consisting of partial responses, were 12.8% [95% confidence interval (CI) 4% to 35%] for gemcitabine-irinotecan and 23.1% (95% CI 10% to 42%) for gemcitabine-docetaxel. Median overall survival was 7.95 months (95% CI 5.2-10.2) and 12.8 months (95% CI 7.9-17.1) for gemcitabine-irinotecan and gemcitabine-docetaxel, respectively. The corresponding estimated 1-year survivals were 23% and 51%, respectively. The 2-year survival rate in arm A (gemcitabine-irinotecan) is not currently estimable. The 2-year survival rate for arm B (gemcitabine-docetaxel) is 22% (95% CI 6% to 37%). Both combinations were well tolerated; the most common hematological toxicity was neutropenia, which occurred in 26% of patients in each treatment arm. CONCLUSIONS: These results suggest that gemcitabine plus docetaxel or irinotecan is well tolerated in patients with chemotherapy-naïve advanced NSCLC. The survival data with the combination gemcitabine-docetaxel are promising. Gemcitabine-docetaxel combination therapy may be particularly useful for patients who have experienced toxicities with a platinum regimen or in patients who may be more susceptible to platinum-related toxicity.

Estradiol selectively affects processing of conspecifics' faces in female rhesus monkeys.

Estrogen deficiency following ovariectomy or menopause increases the risk of developing diseases such as osteoporosis and may also lead to memory impairment. Although estrogen replacement therapy (ERT) alleviates many symptoms associated with estrogen loss, it is not clear whether it also benefits cognitive function. The effect of estrogens upon cognition can best be studied in an animal model of human menopause, in which estrogen levels can be experimentally manipulated. Six young ovariectomized female rhesus monkeys (6-9 years old) were tested on a battery of touchscreen-based cognitive tasks, including the Matching-to-Sample (MTS) task with mixed delays and the spatial, object, and face conditions of the Delayed Recognition Span Test (DRST). Monkeys were tested 5 days a week, one task per week, for a total of 8 months, while undergoing treatments with placebo and ethinyl estradiol (EE2) in alternating 28-days blocks. Blood samples were collected to verify EE2 levels. We also observed the monkeys by video monitor during test sessions and recorded locomotor activity and response topology. Performance on the face-DRST, a task that involved selecting the new face in an increasing array of rhesus monkey faces, was impaired by EE2 treatment, as compared to placebo. Other tasks were unaffected by EE2. There was no clear evidence of EE2 effects upon motor activity or anxiety. In order to test the reliability of our findings, we conducted an additional experiment in which the monkeys were again given the face-DRST with different categories of face stimuli for 4 months, while receiving placebo and EE2 in alternating 7-days blocks. They performed each task 4-5 days/week for 4 weeks with (1) the same rhesus monkey faces as in the first experiment, (2) human faces, (3) chimpanzee faces, and (4) novel rhesus monkey faces. Face-DRST performance did not vary as a function of treatment when human or chimpanzee faces were used as stimuli. In contrast, periods of EE2 treatment were associated with a lower performance for both sets of rhesus monkey faces. These findings suggest that EE2 treatment has a detrimental effect on processing faces of conspecifics by female rhesus monkeys. We speculate that estrogens may produce this effect by enhancing emotional reactivity to socially relevant stimuli.

Nuclear georeactor origin of oceanic basalt 3He/4He, evidence, and implications.

Nuclear georeactor numerical simulation results yield substantial (3)He and (4)He production and (3)He(4)He ratios relative to air (R(A)) that encompass the entire 2-SD (2sigma) confidence level range of tabulated measured (3)He(4)He ratios of basalts from along the global spreading ridge system. Georeactor-produced (3)He(4)He ratios are related to the extent of actinide fuel consumption at time of production and are high near the end of the georeactor lifetime. Georeactor numerical simulation results and the observed high (3)He(4)He ratios measured in Icelandic and Hawaiian oceanic basalts indicate that the demise of the georeactor is approaching. Within the present level of uncertainty, one cannot say precisely when georeactor demise will occur, whether in the next century, in a million years, or in a billion years from now.

The health-related quality of life and survival of small-cell lung cancer patients: results of a companion study to CALGB 9033.

The purposes of this study were 2-fold: to evaluate the impact of the schedule dependency of etoposide (3-day IV short course vs. a 21-day oral prolonged course) with cisplatin on the quality of life of small-cell lung cancer (SCLC) patients; and to examine the effect of baseline quality of life variables on long-term survival, after adjustment for known demographic and clinical prognostic factors. Participants were 70 patients enrolled in the cancer and leukemia group B (CALGB) protocol 9033. Quality of life was assessed at baseline, 6 and 12 weeks by: the EORTC QLQ-30, the Centers for epidemiology studies--Depression short form, the medical outcomes study (MOS) social support questionnaire, and a scale of sleep quality. Contrary to expectations, study results suggested no significant differences in the patients' life quality and treatment response based on whether they received etoposide in a 3-day IV vs. a 21-day oral regimen. The use of the baseline variables in predicting overall survival indicated that patients who were non-white and with liver involvement had decreased survival. Brain involvement, being male, and higher depressive symptoms were also found to be borderline significant in predicting decreased survival in this patient population.

A minimally invasive method for the determination of force in the interosseous ligament.

OBJECTIVE: The objective was to develop and utilize a minimally invasive testing system to determine the force in the interosseous ligament under axial compressive loads across the range of motion of the human forearm. DESIGN: Eleven fresh frozen human cadaveric forearms were used (51-72 years). BACKGROUND: Current studies investigating interosseous ligament forces altered the structure of the forearm by implanting load cells into the radius and ulna. This may affect load transfer through the forearm. Little information was available on interosseous ligament function over the entire flexion range of the elbow. METHODS: A robotic joint testing system was used to apply a 100 N compressive load to the forearm and measure the resulting displacement. Each forearm was tested with no disruption of the bones and soft tissues of the forearm. The principle of superposition was used to calculate the forces in the interosseous ligament and was indirectly validated using fluoroscopy. RESULTS: The force in the interosseous ligament ranged from a minimum of 8 N in neutral forearm rotation at full extension to a maximum of 43 N in supination at 30 degrees of flexion. The largest force was found in supination at all flexion angles. CONCLUSIONS: The interosseous ligament is an important structure in the stability of the forearm. The force in the interosseous ligament depends on the elbow flexion angle and forearm rotation. RELEVANCE: This study suggests that radial head fractures are best treated with the forearm in supination, since the interosseous ligament takes the largest load in this position. Complex injuries which have a poor prognosis, may require interosseous ligament reconstruction to improve clinical outcomes.

Stage distribution in patients with a small (< or = 3 cm) primary nonsmall cell lung carcinoma. Implication for lung carcinoma screening.

BACKGROUND: Recently, there has been increased interest in the use of computed tomography (CT) for lung carcinoma screening. For this technique to be effective, small tumors must be detected at an earlier stage than large lesions. However, to the authors's knowledge, the relationship between the size of small primary (< or = 3 cm) neoplasms and disease stage at presentation has never been established clearly. The current study was performed to determine whether smaller lesions indeed have an earlier stage distribution compared with larger tumors. METHODS: The Duke University Medical Center Tumor Registry identified 620 patients (261 women and 359 men, with a mean age of 67 years) who presented with pathologically proven primary nonsmall cell lung carcinomas measuring < or = 3 cm between 1980-1999. Surgical, pathologic, and imaging information was reviewed retrospectively to confirm the size of the lesion and the disease stage at the time of presentation. The distribution of tumor size within each stage and the distribution of disease stage according to tumor size were determined. RESULTS: Tumors occurring in patients with TNM Stage IIIB disease were slightly larger than those found in patients with either more advanced or less advanced disease. However, there was no apparent statistically significant relation between the stage distribution and the size of the primary lesion. CONCLUSIONS: The current study data did not find a statistically significant relation between the size of small primary lung tumors and the distribution of disease stage at the time of presentation. This finding suggests that the detection of small tumors using screening CT may not result in a shift to an earlier disease stage distribution. A reduction in mortality needs to be demonstrated by appropriate clinical trials prior to the initiation of mass CT screening programs.