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Pormelia sulcata Taylor was used as a model to examine the effects of elevated CO

Fosfomycin has been shown to have a wide spectrum of activity against multidrug-resistant gram-negative bacteria; however, breakpoints have been established only for Escherichia coli or Enterobacterales per the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), respectively. Lack of additional organism breakpoints limits clinical use of this agent and has prompted extrapolation of these interpretive categories to other organisms like Pseudomonas aeruginosa without supporting evidence. Further complicating the utility of fosfomycin is the specified method for minimal inhibitory concentration determination, namely agar dilution, which is not widely available and is both labor- and time-intensive. We therefore sought to determine the susceptibility of a large international collection of P. aeruginosa isolates (n = 198) to fosfomycin, and to compare testing agreement rates across four methods: agar dilution, broth microdilution, disk diffusion, and Etest. Results were interpreted according to CLSI E. coli breakpoints with 49.0-85.8% considered susceptible, dependent upon the testing method used. Epidemiological cutoff values were calculated and determined to be 256 μg/mL or 512 μg/mL for agar dilution and broth microdilution, respectively. Agreement rates were analyzed using both agar dilution and broth microdilution with a resulting high essential agreement rate of 91.3% between the two susceptibility testing methods. These results indicate that broth microdilution may be a reliable method for fosfomycin susceptibility testing against P. aeruginosa and stress the need for P. aeruginosa-specific breakpoints.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 and has quickly become a worldwide pandemic. In response, many diagnostic manufacturers have developed molecular assays for SARS-CoV-2 under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) pathway. This study compared three of these assays, the Hologic Panther Fusion SARS-CoV-2 assay (Fusion), the Hologic Aptima SARS-CoV-2 assay (Aptima), and the BioFire Defense COVID-19 test (BioFire), to determine analytical and clinical performance as well as workflow., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in December 2019 and has quickly become a worldwide pandemic. In response, many diagnostic manufacturers have developed molecular assays for SARS-CoV-2 under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) pathway. This study compared three of these assays, the Hologic Panther Fusion SARS-CoV-2 assay (Fusion), the Hologic Aptima SARS-CoV-2 assay (Aptima), and the BioFire Defense COVID-19 test (BioFire), to determine analytical and clinical performance as well as workflow. All three assays showed similar limits of detection (LODs) using inactivated virus, with 100% detection, ranging from 500 to 1,000 genome equivalents/ml, whereas use of a quantified RNA transcript standard showed the same trend but had values ranging from 62.5 to 125 copies/ml, confirming variability in absolute quantification of reference standards. The clinical correlation found that the Fusion and BioFire assays had a positive percent agreement (PPA) of 98.7%, followed by the Aptima assay at 94.7%, compared to the consensus result. All three assays exhibited 100% negative percent agreement (NPA). Analysis of discordant results revealed that all four samples missed by the Aptima assay had cycle threshold (Ct) values of >37 by the Fusion assay. In conclusion, while all three assays showed similar relative LODs, we showed differences in absolute LODs depending on which standard was employed. In addition, the Fusion and BioFire assays showed better clinical performance, while the Aptima assay showed a modest decrease in overall PPA. These findings should be kept in mind when making platform testing decisions.

Background Theoretically, the estrogen deprivation induced by aromatase inhibitors (AIs) might cause ischemic heart disease, but empiric studies have shown mixed results. We aimed to compare AIs and tamoxifen with regard to cardiovascular events among older breast cancer patients outside of clinical trials. We hypothesized that AIs increase the risk of myocardial infarction. Methods We identified women age ≥67 years diagnosed with breast cancer from June 30, 2006 to June 1, 2008 in the surveillance, epidemiology, and end results (SEER)-Medicare database, treated with either tamoxifen or an AI, and followed through December 31, 2012. To compare myocardial infarction (MI) risk for the treatment groups of AIs vs tamoxifen, we developed and assigned stabilized probability of treatment weights and used the Fine and Gray model for time to MI with death not related to MI as a competing risk. Results Of the cohort of 5648 women, 4690 were treated with AIs and 958 with tamoxifen; a total of 251 patients developed MI, and 22 patients died of MI during the study period while 476 died of other causes. The hazard for MI was not significantly different between AI vs tamoxifen groups (HR = 1.01, 95% CI 0.72-1.42), after adjusting for the following known MI risk factors at the start of adjuvant therapy: diabetes, ischemic heart disease, congestive heart failure, MI, and peripheral vascular disease. Conclusions In this SEER-Medicare-based population study, there were no significant differences in the risk of MI between AI and tamoxifen users after adjustment for known risk factors.

Background Fosfomycin combination therapy is a potential approach for treatment of multidrug-resistant (MDR) PA infections despite a lack of approved susceptibility breakpoints for this organism. While DD testing is commonly used for fosfomycin, growth of discrete inner colonies (IC) within the zone of inhibition has been observed for multiple organisms following DD. Criteria recommended by CLSI and EUCAST are contradictory for interpreting these inner colonies. We therefore sought to determine the frequency of inner colonies and MIC differences between PA parent-inner colony pairs from an international isolate collection. Methods A convenience collection of 198 clinical PA isolates from three U.S institutions (n = 82), two Australian institutions (n = 72), and the CDC & FDA Antibiotic Resistance Isolate Bank (n = 44) were included. Fosfomycin MIC values were determined in duplicate on separate days by DD and broth microdilution (BMD) testing. For parent isolates with discrete IC observed during DD, IC isolates were subcultured and MIC values were determined and then compared to their corresponding parent isolates. MIC values were interpreted using CLSI Escherichia coli (EC) breakpoints (susceptible: MIC ≤ 64 μg/mL, intermediate: MIC = 128, resistant: MIC ≥ 256 μg/mL). Results Parent isolate BMD MIC values ranged from < 4 to > 256 μg/mL while IC isolate BMD MIC values ranged from 128 to > 1024 μg/mL. MIC50/90 values were 128/256 μg/mL and > 1024/ > 1024 μg/mL for the parent and IC isolates, respectively. A high frequency of 45% (89/198) of parent isolates displayed discrete IC which also demonstrated a higher frequency of resistance (97.8%) compared to the parent isolates (23.7%). Conclusion IC MIC values were higher overall compared to parent MIC values, with an average fold difference of ~18 between the parent-inner colony pairs. The frequency of IC found in this study (45%) is considerably higher than previously observed in EC clinical isolates. These data highlight the need to further investigate the importance of these IC and warrant caution for extrapolation of EC breakpoints for fosfomycin susceptibility testing against PA. Disclosures All Authors: No reported disclosures

13 Background: Early detection of lung cancer provides the best opportunity for long-term survival. In 2021 US Preventive Services Task Force (USPSTF) expanded the 2013 risk-based Low-dose CT (LDCT) screening criteria, in part to reduce unintended race and gender disparities in lung cancer detection. We evaluated the impact of the updated USPSTF criteria in a cohort of patients from an incidental lung nodule program (ILNP). Methods: We implemented an ILNP in a community healthcare system in the mid-south US. Patients with lung lesions on routinely-performed radiologic studies were triaged using evidence-based guidelines. We prospectively tracked patient demographics, clinical characteristics, procedures, complications, and health outcomes. We classified all patients in the ILNP cohort based on USPSTF 2013 and 2021 screening criteria. Statistical analysis used the chi-square test. Results: The ILNP cohort included 14,642 patients from 2015-2021. This cohort was 56% female, 65% White, 29% Black, with a median age of 64 years. Overall 1,581 (10.8%) met 2013 and 2,051 (14.0%) met 2021 USPSTF criteria. 1.9% of subjects eligible by 2013 criteria were diagnosed with lung cancer compared to 2.2% by 2021 criteria. 470 additional patients met screening criteria when we expanded from USPSTF 2013 to 2021. As expected, these patients were younger and less likely to have Medicare insurance. These additional eligible patients were significantly more likely to be female (58% v 49%, p = 0.0011) or Black (28% vs. 18%, p < 0.0001) compared to those eligible by 2013 criteria. 44 of the 470 (9%) were diagnosed with cancer: 36% adenocarcinoma, 18% squamous, and 11% small cell, 11% non-lung primary, 9% non-small cell lung cancer NOS, and 15% other or unknown histology. The median tumor size was 3 cm with an interquartile range from 1.7 to 4.2 cm. The clinical stage distribution was 34% I, 4.5% II, 15.9% III, and 31.8% IV. Conclusions: In this selective community-based cohort, USPSTF 2021 criteria identified a higher percentage of subjects with lung cancer and were more inclusive of women and minorities compared to USPSTF 2013 criteria.

Although users of aromatase inhibitors have higher total fracture risk in some randomized trials, little is known about their risk outside of clinical trials or in older higher-risk cohorts. In a population-based retrospective cohort study, we identified all older US Medicare D prescription drug insurance plan-enrolled women who had initial breast cancer surgery in 2006–2008 and began hormonal therapy (an aromatase inhibitor (AI) or tamoxifen) within the subsequent year. Total nonvertebral and hip fractures through 2012 were identified using a validated algorithm. The association of fracture outcomes with hormonal therapy type was assessed using competing risk regression models that accounted for differences in measured baseline covariates. Treatment assignment bias was reduced using inverse probability of treatment weighting computed from propensity scores. Among 23,378 women taking hormonal therapy (23.2% aged 80 or over), there were 3000 total and 436 hip fractures. Although AI users were younger and had lower comorbidity, after propensity score weighting, these and other covariates were balanced. Total nonvertebral risk was higher for users of AIs compared with tamoxifen, HR 1.11 (1.02–1.21), but the small increase in risk for hip fracture was not statistically significant, HR 1.04 (0.84–1.30). Although total nonvertebral fracture risk was higher among AI users, differences in hip fractures were not significant in a large population-based cohort of older women. Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.

Purpose: Aromatase Inhibitors (AIs) are the current standard of care for post-menopausal adjuvant endocrine breast cancer therapy either following or in place of tamoxifen. While their short-term side effect profile was favorable in most studies, findings were mixed regarding cardiotoxicity, and cardiac outcome definitions were not consistent across studies. Given the five or more year duration of adjuvant endocrine therapy, risk of cardiotoxicity in older patients with pre-existing comorbidities remains a particular concern. We examined Myocardial Infarction (MI) as the cardiac outcome in subjects who received AIs vs. tamoxifen in a cohort of Medicare-based breast cancer survivors. Patients and Methods: We identified women age ≥ 67 years diagnosed with breast cancer from 6/30/2006 to 6/01/2008 in the Surveillance, Epidemiology, and End Results-Medicare (SEER) database , with the following eligibility criteria: stage I-III breast cancer, continuous enrollment in Medicare Parts A and B for 24 months prior to the diagnosis and Part D enrollment for one month after the breast cancer diagnosis to the end of follow up (12/31/2012), adjuvant endocrine therapy (tamoxifen or AI fill) within 12 months after diagnosis. The main study outcome was the time to first diagnosis of MI after initiation of AIs or tamoxifen. MI was defined precisely by ICD9 and ICD10 codes relating both to incidence and death from MI. We developed and assigned stabilized inverse proportion weights to balance the groups, and performed a Fine and Gray hazards model for the outcomes of MI and death for the treatment groups of AIs vs tamoxifen. Results: Of the cohort of 5,648 women, 4,690 were treated with AIs and 958 with tamoxifen; a total of 251 patients developed and/or died of MI during the study period while 476 died of other causes. The Fine and Gray Model results in a hazard ratio (HR) were not significantly different from one for weighted AI vs Tamoxifen groups [HR=1.01, C.I. 0.72-1.42]. Covariates which significantly affected the risk of MI were previous diabetes, prior other heart disease, prior congestive heart failure, prior MI, and prior peripheral vascular disease. Other covariates included in the weighted model, were age, American Joint Committee on Cancer (AJCC) cancer stage, chemo, Estrogen and progesterone receptor status, low income subsidy, marital status, prior hypertension, prior stroke, per capita income, race, radiation, SEER region, and urbanization. Conclusions: The occurrence of MI is very low in this cohort (4.4%), reassuring the clinicians that the older adults with comorbidities may not be at a higher risk of MI with adjuvant endocrine therapy. However, the confidence interval for the hazard ratio of AIs vs Tamoxifen is very wide, indicating that a larger sample may be needed for the power of the study to be conclusive. Citation Format: Kamaraju S, Smith E, Shi Y, Laud P, Neuner J. Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD4-07.

Background: One of the benefits of neoadjuvant approach to the treatment of breast cancer is early microscopic disease control, which should translate to improved survival. However, clinical trials have not yet shown a survival benefit for neoadjuvant approach in even high risk patients, such as triple negative cases. Few studies have been performed outside of clinical trials. Purpose: The objective of our study was to compare the overall survival of Stage I-III triple negative breast cancer patients who received neoadjuvant vs adjuvant chemotherapy within the NCDB, a prospectively collected, large, nationwide, hospital-based cancer outcomes database which contains information for more than 1,500 Commission on Cancer-accredited cancer programs in the U.S. Patient and Method: We identified a cohort of women, aged > 18 year-old at diagnosis, with clinical stage I-III triple negative breast cancer diagnosed in 2010-2011, who received either neoadjuvant chemotherapy only or adjuvant chemotherapy only. Patients with incomplete or missing vital status, receptors status and treatment information were excluded. Demographic (age at diagnosis, race, ethnicity, comorbidities, insurance, median income, urbanicity), tumor (clinical stage, histology, grade) and treatment (breast surgery, surgical margin, radiation) factors were examined. Stabilized inverse proportion weights were developed and assigned to balance the neoadjuvant and adjuvant groups on all demographic, tumor and treatment covariates. Unadjusted and adjusted overall survival was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: Among the 15,483 women with triple negative breast cancer, 4,335 (28%) received neoadjuvant chemotherapy and 11,148 (72%) received adjuvant chemotherapy. Most of the demographic, tumor and treatment factors were similarly distributed among neoadjuvant and adjuvant groups except age at diagnosis and clinical stage. Compared to patients received adjuvant chemotherapy, patients received neoadjuvant chemotherapy were more likely to be younger (45% vs. 31% < 50 year-old, p Conclusion: In this NCDB study, the overall survival of triple negative breast cancer patients received neoadjuvant chemotherapy was inferior to those received adjuvant chemotherapy, even after adjusting for demographic, tumor and treatment factors. However, information regarding the chemotherapy regimen used and whether a full course of chemotherapy was delivered (2 factors that affect disease response and outcome) was not available. Patient and tumor factors at the time of disease presentation that are important in determining which triple negative patients will benefit from neoadjuvant approach remain to be defined. Citation Format: Cheng YC, Smith E, Yen T. Overall survival of patients with non-metastatic triple negative breast cancer who received neoadjuvant vs adjuvant chemotherapy: Cohort analysis of National cancer data base (NCDB) 2010 - 2011 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-09.

Background FOF has been used in the treatment of multidrug-resistant (MDR) KP infections despite established susceptibility breakpoints. At present, agar dilution (AD) is considered the reference method for FOF while broth microdilution (BMD) is specifically recommended against despite its convenience over AD. We therefore sought to assess FOF activity against KP, along with essential and categorical agreement between AD and BMD methods to determine if BMD could be used as a reliable testing method. Methods Minimal inhibitory concentration (MIC) values were determined for a convenience collection of 69 KP isolates (59.4% MDR) from three US institutions. MIC testing was conducted in duplicate on separate days using AD and BMD methods; essential and categorical agreement were calculated using AD as the reference method. Fourteen isolates were also analyzed using high-inoculum AD (105.3-5.9 CFU/mL) similar to the BMD method. MIC values were categorized using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria for Escherichia coli (≤ 64 mg/L, susceptible). ECVs were determined according to CLSI methodology. Results MIC values varied between methods, withMIC50/MIC90 values being 32/256 mg/L for AD and 128/256 mg/L for BMD. Using E. coli criteria, susceptible/intermediate/resistant rates were 82.6/2.9/14.5% (AD) and 44.9/21.7/33.3% (BMD). Essential agreement was 44.9% and categorical agreement was 60.8%. When using high-inoculum AD, MIC values were on average three-fold higher compared to standard-inoculum AD, with 10 of the 14 (71.4%) isolates brought into essential agreement with BMD. Calculated ECVs were 128 mg/L for standard-inoculum AD and 1024 mg/L for BMD. Conclusion Our collection of KP displayed high MIC values to FOF, in addition to substantial discrepancies between AD and BMD methods. Essential agreement increased with the use of high-inoculum AD testing, which better correlated with BMD results. ECV for BMD was three dilutions higher than that for standard-AD ECV. Based on these results, we recommend further investigation of BMD for FOF testing using a larger isolate collection, along with optimization of currently recommended testing methods. In light of these results, KP-specific breakpoints should also be examined. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

Purpose: There is variability in sensitivity to bitter tastes. Taste 2 Receptor (TAS2R)38 binds to bitter tastants including phenylthiocarbamide (PTC). Many foods with putative cancer preventive activity have bitter tastes. We examined the relationship between PTC sensitivity or TAS2R38 diplotype, food intake, and cancer risk in the UK Women’s Cohort Study. Methods: PTC taste phenotype (n = 5500) and TAS238 diplotype (n = 750) were determined in a subset of the cohort. Food intake was determined using a 217-item food-frequency questionnaire. Cancer incidence was obtained from the National Health Service Central Register. Hazard ratios (HR) were estimated using multivariable Cox proportional hazard models. Results: PTC tasters [HR 1.30, 95% confidence interval (CI) 1.04, 1.62], but not supertasters (HR 0.98, CI 0.76, 1.44), had increased cancer risk compared to nontasters. An interaction was found between phenotype and age for supertasters (p = 0.019) but not tasters (p = 0.54). Among women > 60 years, tasters (HR 1.40, CI 1.03, 1.90) and supertasters (HR 1.58, CI 1.06, 2.36) had increased cancer risk compared to nontasters, but no such association was observed among women ≤ 60 years (tasters HR 1.16, CI 0.84, 1.62; supertasters HR 0.54, CI 0.31, 0.94). We found no association between TAS2R38 diplotype and cancer risk. We observed no major differences in bitter fruit and vegetable intake. Conclusion: These results suggest that the relationship between PTC taster phenotype and cancer risk may be mediated by factors other than fruit and vegetable intake.

Purpose To investigate the role of out-of-pocket cost supports through the Medicare Part D Low-Income Subsidy on disparities in breast cancer hormonal therapy persistence and adherence by race or ethnicity. Methods A nationwide cohort of women age ≥ 65 years with a breast cancer operation between 2006 and 2007 and at least one prescription filled for oral breast cancer hormonal therapy was identified from all Medicare D enrollees. The association of race or ethnicity with nonpersistence (90 consecutive days with no claims for a hormonal therapy prescription) and nonadherence (medication possession rate < 80%) was examined. Survival analyses were used to account for potential differences in age, comorbidity, or intensity of other treatments. Results Among the 25,111 women in the study sample, 77% of the Hispanic and 70% of the black women received a subsidy compared with 21% of the white women. By 2 years, 69% of black and 70% of Hispanic patients were persistent compared with 61% of white patients. In adjusted analyses, patients in all three unsubsidized race or ethnicity groups had greater discontinuation than subsidized groups (white patients: hazard ratio [HR], 1.83; 95% CI, 1.70 to 1.95; black patients: HR, 2.09; 95% CI, 1.73 to 2.51; Hispanic patients: HR, 3.00; 95% CI, 2.37 to 3.89). Racial or ethnic persistence disparities that were present for unsubsidized patients were not present or reversed among subsidized patients. All three subsidized race or ethnicity groups also had higher adherence than all three unsubsidized groups, although with the smallest difference occurring in black women. Conclusion Receipt of a prescription subsidy was associated with substantially improved persistence to breast cancer hormonal therapy among white, black, and Hispanic women and lack of racial or ethnic disparities in persistence. Given high subsidy enrollment among black and Hispanic women, policies targeted at low-income patients have the potential to also substantially reduce racial and ethnic disparities.

Objectives: Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with early-stage, estrogen receptor–positive breast cancer. We designed our study to determine whether women initiating adjuvant therapy with an AI underwent baseline bone mineral density testing, as well as what factors predicted adherence with testing guidelines. Methods: Medicare Parts A, B, and D claims were used to identify a cohort of women aged 67 years and older with incident breast cancer in 2006 and 2007 who started AI therapy. Medicare claims provided information about bone density testing, as well as demographic and other treatment data through 2012. We also ascertained which patients were treated with bisphosphonates and studied the relationship of bisphosphonate therapy with bone density testing. Results: Approximately two-thirds of patients had baseline bone density testing. Older age, comorbidity, low income, and black race were associated with lower rates of baseline bone density testing. Testing rates decreased substantially with increasing age from 73% for women aged 67 to 70 years to 51% for those 85 years of age and older (adjusted odds ratio for not being tested, 2.48 [Cl, 2.17–2.82]). The proportion of women who had neither bone density testing nor bisphosphonate therapy increased with age as well. Conclusions: Despite the importance of age as a risk factor for fractures, older women starting treatment with AIs for treatment of breast cancer are less likely to undergo recommended bone density assessment.

Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

The photosynthetic responses of a range of trebouxioid lichens were investigated to determine whether variations in net assimilation rates shown by populations of the same species collected from different habitats could be correlated with adjustments in carbon-concentrating mechanism (CCM) activity. The activity of a CCM was inferred from the high affinity for CO2 [i.e. low CO2 compensation point (Γ); low external CO2 concentration at which half-maximal assimilation rates are reached (K 0.5 CO2)], the release of a pool of accumulated dissolved inorganic carbon (Ci) during light/dark transient measurements of CO2 exchange and values for carbon isotope discrimination intermediate between those characteristic of C3 and C4 terrestrial plants. Higher net and gross assimilation rates were expressed by lichens collected from shaded woodland habitats. The higher rates were not accounted for by variations in chlorophyll content. Lichens with high assimilation rates also showed an increased affinity for CO2 as demonstrated by low CO2 compensation points and K 0.5 values and the magnitude of the Ci pool accumulated upon illumination and released after darkening of the thalli. However, there was no correlation between assimilation rates and organic matter or instantaneous carbon isotope discrimination measurements, with the latter remaining roughly consistent whatever the provenance or species of the lichen material. The data are discussed with reference to significant environmental factors which are likely to control photosynthesis in the habitats studied.

In discrete choice experiments, survey participants are often asked to consider stated cost, to themselves, as a source of funding of an environmental project. An open question remains whether participants would consider an additional source of funding, such as public or federal support. We examine the impact of federal funding availability on the marginal utility of management attributes and on respondents’ private willingness to pay (WTP) for watershed management plans. Our results suggest that availability of public funding does not significantly alter the preferred tradeoffs among management attributes for active management plans, but alters the utility difference, and therefore the WTP, between an active plan and the status quo alternative. A latent class model further suggests that classes with relatively similar preferences may nonetheless show heterogeneity in how availability of public funds affects WTP for management plans against the status quo, depending on individuals’ sociodemographic profiles and environmental attitudes. Public funding affects WTP through both crowding-in and crowding-out effects. Our results suggest that private responses to public funds may be more complex than previous studies on public goods have suggested, as public funds may neither attract contributions nor crowd out private support uniformly.

Background FOF has been used clinically for the treatment of PA infections in the absence of established interpretive criteria. A recent study identified a low frequency of nonsusceptible inner colony mutants during disk diffusion (DD) testing of Escherichia coli; however, the frequency of this phenomenon in PA isolates is not well characterized. We sought to determine FOF activity against an international collection of PA isolates and the frequency of inner colony mutants observed during Etest and DD testing. Methods Minimal inhibitory concentration (MIC) values were determined for a convenience collection of 109 PA ([70/94] 64.2% MDR) isolates from 4 institutions in the United States and Australia. MIC testing was conducted in duplicate on separate days utilizing agar dilution (AD), broth microdilution (BMD), DD, and Etest as recommended per Clinical and Laboratory Standards Institute (CLSI). CLSI E.coli interpretive criteria (≤ 64 mg/L susceptible) were used for MIC interpretations. The proportion of isolates containing inner colonies was determined using DD and Etest. Inner colony mutants were subcultured and retested using BMD with comparison to the parent isolate MICs. Results FOF MICs varied widely and ranged from 1024 mg/L with MIC50/MIC90 values of 64/256 (AD), 64/512 (Etest), and 64/256 (BMD) mg/L. Using E. coli criteria, susceptible/resistant rates were: 60.5/17.4% for AD; 60.5/22.0% for Etest; 86.2/7.3% for DD; and 53.2/17.4% for BMD. Inner colonies were frequently observed in 38.5% and 35.8% of DD and Etest inhibition zones, respectively. After repeat testing, mutant MIC values ranged from 64 to > 1024 mg/L and a majority (85.9%) had MIC values ≥ 512 mg/L. Conclusion Observed MIC values of this (64% MDR) collection varied widely with MIC50/90 values commonly at or above the E. coli susceptibility breakpoint. Inner colony mutants were frequently observed and highly resistant. Whole-genome sequencing is currently underway for a subset of parent/mutant pairs to determine whether specific genetic alterations are attributed to the increased MICs. Based on these results, caution should be warranted in extrapolating E. coli breakpoints to other organisms, and treatment of PA with FOF should be further evaluated. Disclosures Elizabeth B. Hirsch, PharmD, Merck: Grant/Research Support, Research Grant; Nabriva Therapeutics: Advisory Board; Paratek Pharmaceuticals: Advisory Board.

Background: Endocrine therapies, particularly aromatase inhibitors, substantially reduce breast cancer mortality in clinical trials. High rates of cost-related nonadherence to these long-term oral medications, however, have reduced their population-wide impact. While the 2006 Medicare Part D introduction promised to improve this situation, most Part D enrollees’ out-of pocket aromatase inhibitor costs actually remained high and rose steadily over subsequent years. We examined the effect of a natural experiment which lowered these costs—anastrozole patent expiration—upon endocrine therapy adherence among a nationwide sample of breast cancer patients. Methods:Our sample included all female Medicare beneficiaries aged > = 66 identified (using a validated Medicare claims algorithm) as having incident breast cancer surgery in 2006-07 who also had one or more Part D claim for an aromatase inhibitor or tamoxifen between 7/1-12/30/2008. Part D claims were used to calculate adherence, defined as medication possession ratio (MPR)>80%, and medication out-of-pocket costs. A binary outcome regression model with a logit link was estimated using generalized estimating equations to study the effect of FDA approval of generic anastrozole (7/1/2010) upon adherence. The model was also adjusted for patient sociodemographic and health characteristics (age, race, comorbidities), time since surgery, low-income subsidy (LIS) (which lowers copays and eliminates the Medicare D “donut hole”) and temporal trend. Results: The mean out-of-pocket medication cost for the 22,203 cohort members (85% white, 47% age > = 75, 31% low income subsidy recipients, 45% anastrozole users) was $205 in the first quarter of 2009. Cohort members’ adherence to endocrine therapies dropped 15.8% from 72% in the first quarter to 61% in the last quarter during the pre-generic year (2009). In contrast, adherence was reduced by less than half that amount (-6.3%) between the same time periods in 2010 once anastrozole went generic. In adjusted models, both generic anastrozole availability and receipt of a low income subsidy were strongly associated with greater adherence to hormonal therapy (table). White race, younger age, and lower comorbidity all had smaller but statistically significant associations with greater adherence. There were no significant interactions between variables. Adherence to Adjuvant Endocrine Therapy with Availability of Generic AnastrozoleFactorOdds Ratio95 CIP valueGeneric Anastrozole2.642.38 to 2.94.001Low Income Subsidy1.961.76 to 2.20.001also adjusted for year, quarter of year, comorbidity, race, age Conclusions and Implications: The introduction of generic anastrozole was associated with a substantial and clinically significant improvement in endocrine therapy adherence among Medicare Part D enrollees. Such results have generally not been observed in studies of generic medications for chronic diseases, and may partly reflect increasing out-of-pocket demands by insurers. These findings, along with our findings of better adherence among low income subsidy recipients, highlight the importance of regulatory and subsidy policies for patients requiring long-term cancer medications. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-01.

Urban particulate matter (UPM) contributes to lung cancer incidence. UPM has been shown to be genotoxic to mammalian cells and to induce mutations in the Ames assay. Here, we have studied the induction of mutations generated by direct acting mutagenic components of UPM, using the supF forward mutation assay. Plasmid pSP189 was exposed to UPM in aqueous solution in the presence of sucrose buffer, to reduce strand breaks. The mutation frequency induced by 1 microg/microl UPM was 4.99 mutants per 10(4) colonies. This was reduced to 0.84 and 1.48 mutants per 10(4) colonies by addition of mannitol (1 mM) or EDTA (1 mM), respectively. A large percentage of mutant plasmids contained frameshift mutations (57%), and 31% of mutant plasmids contained multiple mutations. Of the base substitution mutations, 88% were at GC pairs, with twice as many transversions as transitions. The types of mutations induced, the reduction of mutagenicity by the inclusion of the free radical scavenger, mannitol, or the metal chelator, EDTA, and the sequence context of the induced mutations all support the conclusion that the majority of mutations were induced by reactive oxygen species generated by metal ions present in the UPM. Most mutation studies with UPM have focused on organic carcinogens present on UPM. Our results highlight the potential contribution of metal ions to the mutagenicity of UPM.

Production of parasite-specific antibodies is an important component of immunity to blood stage malaria infection, as shown by several previous studies in rodent models. However, no study has addressed the induction of humoral immunity by different parasites in a genetically homogeneous host population. Here, levels of parasite-specific immunoglobulin isotypes were measured during primary infections of Plasmodium chabaudi and of Plasmodium yoelii in inbred NIH mice inoculated with cloned lines of either avirulent or virulent erythrocytic parasites. Non-lethal infections were characterized by early and late significant upregulation of IgG2a and IgG1, respectively. In contrast, for lethal infections, a slower, reduced IgG2a response correlated with a rapidly fatal outcome prior to any significant synthesis of IgG1. It is proposed that the sequential upregulated synthesis of parasite-specific IgG2a (cytophilic) and IgG1 (non-cytophilic) is associated with protective immunity to blood stage malaria infections in mice. This may provide an immunological framework for examining humoral immunity to malaria in humans.

There are over twenty oral antineoplastics currently approved in the United States and dozens more on the horizon (1). Adjuvant tamoxifen therapy for hormone receptor–positive breast cancer was one of the earliest developed long-term oncologic therapies. When taken for five to 10 years, it reduces long-term breast cancer mortality by one-third to one-half (2–4). The newer aromatase inhibitors anastrozole, letrozole, and exemestane reduce cancer recurrence by an additional 50% (5) but also need to be taken either alone or after tamoxifen for at least five total years of endocrine therapy (5). Unfortunately, many breast cancer patients prescribed long-term oral therapies have trouble adhering to them (6). One-third to one-half of patients prescribed adjuvant endocrine therapy (ET) outside of clinical trials either discontinue or adhere poorly to their medication within the first three years of therapy (7–15). Endocrine therapy nonadherence has clinically important effects. In one large breast cancer cohort, poor adherence to tamoxifen or aromatase inhibitors as measured by prescription fills was associated with a reduction in survival of 4% to 8% (16). There is increasing evidence that patient out-of-pocket costs play an important role in endocrine therapy nonadherence (17,18). The aromatase inhibitors (AIs) are substantially more costly than the generic tamoxifen, and many insurers are requiring that patients pay higher out-of-pocket costs for more expensive medications (17,18). In one recent study, 27% of patients in 2005 to 2008 with commercial insurance paid over $30 monthly out-of-pocket for their adjuvant aromatase inhibitor; adherence in this high-copay group was 18% to 28% lower than for patients paying $10 or less (17). In July 2010, an opportunity for reversal of these trends arose with the patent expiration of anastrozole. In contrast to some generic medications that face little competition when first released, thirteen generic manufacturers had generic anastrozole approved by the month after patent expiration, offering the potential for competition by cost. Shortly thereafter (April 2011), generic letrozole and exemestane were also released. Medicare D pharmaceutical program enrollees comprise an ideal national, population-based cohort in which to examine the adherence effects of this natural experiment. The Medicare D program required that all antineoplastic agents be on plan formularies. Furthermore, it provided a low-income subsidy (LIS) program to a substantial number of Medicare D enrollees, providing premium, deductible, and copayment support (including during the coverage gap or “donut hole” period) for enrollees with household incomes up to 150% of the federal poverty line. LIS recipients who experienced small or no effects upon out-of-pocket costs as generics became available thus could be compared with those without such supports, who experienced substantial changes in costs (18). The purpose of this study was to examine the effect of the introduction of generic versions of aromatase inhibitors on adherence to endocrine therapy among a nationally representative sample of elderly women with incident breast cancer using a quasi-experimental pre-post study design. We hypothesized that the well-documented rate of decline in adherence over time would be substantially attenuated after generic AIs became available. We further hypothesized that the effects would be larger for those not enrolled in the low-income subsidy program for pharmaceutical coverage.

The role of carbonic anhydrase in the carbon-concentrating-mechanism of bryophytes of the class Anthocerotae was investigated by comparing the gas-exchange characteristics of material which had been incubated in the membrane-permeable Carbonic Anhydrase inhibitor ethoxyzolamide, with those of untreated material and material which had been incubated in buffer solution. In Phaeoceros laevis (Anthocerotae), incubation in ethoxyzolamide caused a depression in the rate of gross assimilation and a decrease in CO2 affinity beyond that which could be attributed to increased diffusion limitation. A range of liverworts and mosses, in which a carbon- concentrating-mechanism is absent, were also investigated. These showed no depression of rates of gross assimilation after incubation in ethoxyzolamide relative to those of untreated material. The CO2 compensation point and CO 2 uptake characteristics of Phaeoceros laevis were significantly affected by incubation in ethoxyzolamide. Values of CO2 compensation point for Phaeoceros laevis rose from 2.5 Pa, after incubation in buffer, to 20 Pa after incubation in ethoxyzolamide. The CO2 compensation point for the liverworts Pellia epiphylla and Marchantia polymnorpha was not significantly affected by incubation in ethoxyzolamide. Measurements of the release of CO2 at the end of a short (15 min) period of illumination revealed that, after suppression of carbonic anhydrase activity, the rapid release of a CO2 pool occurred in Phaeoceros laevis but not in the liverworts. There were also significant differences between values for fractionation measured in units per mil (%oo), measured instantaneously, for Phaeoceros laevis incubated in ethoxyzolamide, compared with fractionation values for this species after incubation in buffer. Incubation in ethoxyzolamide caused fractionation values to rise from 12.4-22.7%o, indicating that the carbon-concentrating-mechanism of this species had been inactivated. Incubation in ethoxyzolamide had no effect on fractionation values for the liverworts. The convexity of the light saturation curves of liverworts and Phaeoceros laevis was also investigated, but there were no differences between groups before or after the two treatments. The data indicate an important role for carbonic anhydrase in the functioning of the carbon-concentrating-mechanism in the Anthocerotae.

Malaria is the world's major parasitic disease, for which effective control measures are urgently needed. One of the difficulties hindering successful vaccine design against Plasmodium is an incomplete knowledge of antigens eliciting protective immunity, the precise types of immune response for which to aim, and how these can be induced. A greater appreciation of the mechanisms of protective immunity, on the one hand, and of immunopathology, on the other, should provide critical clues to how manipulation of the immune system may best be achieved. We are studying the regulation of the balance between T helper 1 (Th1) and T helper 2 (Th2) CD4+ T lymphocytes in immunity to asexual blood stages of malaria responsible for the pathogenicity of the disease. Protective immunity to the experimental murine malarias Plasmodium chabaudi and Plasmodium yoelii involves both Th1 and Th2 cells, which provide protection by different mechanisms at different times of infection characterised by higher and lower parasite densities, respectively. This model therefore facilitates a clearer understanding of the Th1/Th2 equilibrium that appears central to immunoregulation of all host/pathogen relationships. It also permits a detailed dissection in vivo of the mechanisms of antimalarial immunity. Here, we discuss the present state of malaria vaccine development and our current research to understand the factors involved in the modulation of vaccine-potentiated immunity.

Nitric oxide (NO) is cytotoxic and cytostatic to blood stage malaria parasites in vitro, but the precise mechanism(s) by which it mediates an effect in vivo is not known. In particular, whether or not control of acute parasitemia depends on the presence of NO is unclear. We have shown previously that blocking NO synthesis at the time of its induction may cause an increase in peak primary parasitemia during infection of mice with Plasmodium chabaudi, suggesting that NO may be parasiticidal in vivo. However, as recent data indicate that NO suppresses Th1 cell proliferation in vitro by downregulating IL-2 production, we have investigated whether this immunoregulatory function of NO affects its capacity for anti-malarial activity. Treatment of P. chabaudi-infected mice with the iNOS inhibitor aminoguanidine hemisulfate (AG) starting just prior to the peak of primary parasitemia caused a significant elevation and extension of the acute infection and led to a partial but significant abrogation of the suppression of spleen cell proliferation to both mitogen and specific antigen observed when NO synthesis was not blocked. In the absence of NO, levels of IL-2, but not of IFN-gamma, TNF-alpha, or of any Th2-regulated cytokines examined, increased significantly. However, when AG treatment was brought forward to the early ascending phase of primary parasitemia, significantly increased levels of IFN-gamma and TNF-alpha, as well as of IL-2, were observed over those for infected control mice similarly treated with phosphate-buffered saline. Moreover, despite the absence of NO, parasitemias of AG-treated mice were not significantly elevated. The effect of AG therefore appeared to be dependent upon the timing of its administration in vivo. We propose that during malaria infections, there is a dynamic balance between the regulatory and anti-parasitic roles of NO. While the immunosuppressive function of NO leads to a downregulation in vivo of production of IL-2, and indirectly of IFN-gamma and TNF-alpha, this perceived weakening of the host cell-mediated immune response is in part masked by the protective anti-malarial effects of NO itself.

summary Pormelia sulcata Taylor was used as a model to examine the effects of elevated CO2 and/or O3 on green algal lichens. Thalli were exposed for 30 d in duplicate controlled-environment chambers to two atmospheric concentrations of CO2 (‘ambient’ [350μmol mol−1] and ‘elevated’ [700μmol mol−1] 24 h d−1) and two O3 regimes (‘non-polluted’ air [CF, < 5 nmol mol−1] and ‘polluted’ air [15 nmol mol−1overnight rising to a midday maximum of 75 nmol mol−1]), in a factorial design. Elevated CO2, or elevated O3 depressed the light saturated rate of CO2, assimilation Asat) measured at ambient CO2, by 30% and 18%, respectively. However, despite this effect ultrastructure) studies revealed increased lipid storage in cells of the photobiont in response to CO2-enrichment. Simultaneous exposure to elevated O3 reduced CO2-induced lipid accumulation and reduced Asat in an additive manner. Gold-antibody labelling revealed that the decline in photosynthetic capacity induced by elevated CO2and/or O3 was accompanied by a parallel decrease in the concentration of Rubiscoa in the algal pyrenoid (r= 0.93). Interestingly, differences in the amount of Rubisco protein were not correlated with changes in pyrenoid volume. Measurements of in vivo chlorophyll-fluorescence induction kinetics showed that the decline in Asat induced by elevated CO2, and/or O2, was not associated with significant changes in the photochemical efficiency of photosystem (PS) II. Although the experimental conditions inevitably imposed some stress on the thalli, revealed as a significant decline in the efficiency of PS II photochemistry, and enhanced starch accumulation in the photobiont over the fornication period, the study shows that the green-algal lichen symbiosis might be influenced by future changes in atmospheric composition. Photosynthetic capacity, measured at ambient CO2, was found to be reduced after a controlled 30 d exposure to elevated CO2, and/or O3 and this effect was associated with a parallel decline in the amount of Rubisco in the pyrenoid of algal chloroplasts.

LANGUAL, a computer-based food-description language, uses standardized vocabulary to describe specific characteristics of foods and food products. Each food product in a database is described by a set of descriptors from the following factors: product type; food source; part of plant or animal; physical state, shape, or form; extent of heat treatment; cooking method; treatment applied; preservation method; packing medium; container or wrapping; food contact surface; consumer group/dietary use/label claim; geographic places and regions; and adjunct characteristics. The purpose of LANGUAL is to allow rapid, accurate retrieval of food names from food-related databases relative to descriptive terms for these factors. The major advantages of LANGUAL are the speed and specificity of the retrievals and the flexibility of the system relative to change and updating.

In a split sample design, we examine the impact of federal funding availability on Willingness to Pay (WTP) for watershed management program attributes and tradeoffs in a choice experiment. We also evaluate how presenting respondents with different sets of choice attributes, in alternative survey designs, affects the estimation of preference functions. We also compared preferences for watershed management attributes across sub-watersheds. These issues were evaluated using the Blackstone River Watershed Public Preference Survey, in Rhode Island, USA. Our results indicate that neither federal support nor geographically distinct sub-watersheds had significant impact on tradeoffs elicited among management attributes. However, survey design may induce respondents to show distinct preferences for watershed management. We examined these issues using a multinomial logit model in comparison with a Latent Class Model (LCM) to account for heterogeneity in preferences.

White Carneau pigeons have previously been shown to be genetically susceptible to the development of spontaneous atherogenesis. The severity of development of atheromatous lesions is considerably greater than a more resistant breed of Show Racer pigeons. Analysis of levels of total hydroxyproline and isodesmosine in the thoracic aorta and celiac bifurcation of prelesion, six-week-old White Carneau and Show Racer pigeons, revealed an increased accumulation of total collagen and cross-linked elastin in the White Carneau arterial tissue. Using dot blot hybridization, measurements of steady state levels of several mRNAs in total RNA extracted from pigeon aortic tissue were also determined. While the increased deposition of extracellular matrix proteins was paralleled by a significantly greater recovery of mRNAs coding for pro alpha 1(1) collagen and elastin, in RNA extracted from White Carneau aortal tissue, increased recovery of mRNAs coding for an intracellular protein, gamma-actin were also observed in White Carneau aortal tissue. No differences in steady state levels of mRNAs coding for pro alpha 1(1) collagen and elastin were observed in RNA extracted from pigeon liver, suggesting a tissue specific increase in the mRNAs coding for these connective tissue proteins in aorta. A markedly reduced cell population however, was responsible for this overall increase in biosynthetic activity in White Carneau pigeon aortic tissue. This was demonstrated by a reduced cell count and by the recovery of reduced levels of total DNA in the thoracic aorta and celiac bifurcation of the White Carneau pigeon. The cell population in White Carneau aortic tissue exhibits therefore a markedly different phenotype with respect to a capacity for the biosynthesis of extracellular and intracellular proteins.

It has proven difficult to identify those spiders which cause necrotic lesions. In an effort to design a simple, inexpensive screening method for identifying spiders with necrotizing venoms, we have examined the venom gland homogenates of a variety of spider species for their ability to cause red blood cell lysis. Those venoms which were positive were further examined for the presence of sphingomyelinase D, and their ability to evoke necrotic lesions in the skin of rabbits. Sphingomyelinase D is known to be the causative agent of necrosis and red blood cell lysis in the venom of the brown recluse spider (Loxosceles reclusa), and our assumption was that this would be the same agent in other spider venoms as well. This did not prove to be the case. Of 45 species examined, only the venom of L. reclusa and Cheiracanthium mildei lysed sheep red blood cells. Unlike L. reclusa venom, however, C. mildei venom did not possess sphingomyelinase D nor did it cause necrotic lesions in the skin of rabbits. We present evidence suggesting that a phospholipase A2 is the hemolytic agent in C. mildei venom.

The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CVof less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.

2 Background: Breast cancer outcomes are worse among black than white women, but the role of income and out-of-pocket costs (OOPCs) in these disparities is understudied. The Medicare D program provided medication insurance for older women and also included a low-income subsidy (LIS) which eliminated or reduced OOPCs among women with low assets and limited income (based on federal poverty level). We examined differences in adherence to HT by race/ethnicity among a Medicare D population, hypothesizing that LIS might reduce racial disparities in HT adherence. Methods: With data collected from a national sample of women enrolled in Medicare Parts A, B, and D, we identified Medicare Part D enrollees ≥65 years diagnosed with breast cancer who underwent mastectomy or breast conserving surgery in 2006-07 and received either tamoxifen or an AI (anastrozole, letrozole, or exemestane) within one year of surgery. Nonadherence rates (medication possession rate of >0.80) were calculated by race and LIS status for each year after first fill up through December 2011. The association of race with HT adherence was examined in unadjusted Chi-square analyses and in regression models adjusted for age, comorbidity, chemotherapy use, and zip code level- income and education. All models utilized GEE to account for within-patient clustering. Results: Among a sample of 23,299 women (50.6% age 65-74, 40.9% age 75-84), 27.2% received LIS. LIS (but not AI use) varied substantially by race, so that 20.6% of white women and 69.7% of black women received the subsidy. In the first year of therapy, differences in adherence by race were statistically significant, but small (64.2% for white, 63.2% for black and 66.7% for Hispanic). Adherence dropped during years 2-3 of the study, but reductions were much smaller among LIS recipients. Results were confirmed in adjusted models. Conclusions: Enrollment in the Medicare D LIS was high among black and Hispanic breast cancer patients, and disparities in adherence to breast cancer HT among these women were small and remained so over three years. Our study offers important information about the role of medication subsidies and SES in adherence, and suggests their potential to reduce the breast cancer outcomes gap by race.

6642 Background: Because of the adverse effects of AI’s on bone mineral density (BMD) and fracture risk, current guidelines recommend baseline BMD testing when initiating adjuvant AI’s. Methods: We used a validated breast cancer algorithm of Medicare claims to identify older US female breast cancer patients starting adjuvant AI therapy and to examine baseline BMD testing rates. The cohort included all US non-HMO Medicare D-enrolled women age ≥67 years who initiated AI therapy within one year after a 2006-2007 initial breast cancer surgery. Women receiving IV bisphosphonates consistent with metastatic breast cancer treatment (interval

The organic-matter carbon isotope discrimination (Δ) of lichens with a wide range of photobiont and/or cyanobiont associations was used to determine the presence or absence of a carbon-concentrating mechanism (CCM). Two groups were identified within the lichens with green algal photobionts. One group was characterised by low, more C4-like Δ values (Δ 18‰). Tri-partite lichens (lichens with a green alga as the primary photobiont and cyanobacteria within internal or external cephalodia) occurred in both groups. All lichens with cyanobacterial photobionts had low Δ values (Δ < 15‰). The activity of the CCM, organic-matter Δ values, on-line Δ values and gas-exchange characteristics correlated with the presence of a pyrenoid in the algal chloroplast. Consistent with previous findings, lichens with Trebouxia as the primary photobiont possessed an active CCM while those containing Coccomyxa did not. Organic Δ values for lichens with Stichococcus as the photobiont varied between 11 and 28‰. The lichen genera Endocarpon and Dermatocarpon (Stichococcus + pyrenoid) had C4-like organic Δ values (Δ = 11 to 16.5‰) whereas the genus Chaenotheca (Stichococcus — pyrenoid) was characterised by high C3-like Δ values (Δ = 22 to 28‰), unless it associated with Trebouxia (Δ = 16‰). Gas-exchange measurements demonstrated that Dermatocarpon had an affinity for CO2 comparable to those species which possessed the CCM, with K0.5 = 200–215 μ1 · 1−1, compensation point (Γ) = 45–48 μl · l−1, compared with K0.5 = 195 μ1 · 1−1, Γ = 44μ1 · 1−1 for Trebouxioid lichens. Furthermore, lichens with Stichococcus as their photobiont released a small pool (24.2 ± 1.9 to 34.2 ± 2.5 nmol · mg−1 Chl) of inorganic carbon similar to that released by Trebouxioid lichens [CCM present, dissolved inorganic carbon (DIC) pool size = 51.0 ± 2.8 nmol · mg−1 Chl]. Lichens with Trentepohlia as photobiont did not possess an active CCM, with high C3-like organic Δ values (Δ = 18‰ to 23‰). In particular, Roccella phycopsis had very high on-line Δ values (Δ = 30 to 33‰), a low affinity for CO2 (K0.5 = 400 μ1 · 1−1,Γ = 120 μ1 · −1) and a negligible DIC pool. These responses were comparable to those from lichens with Coccomyxa as the primary photobiont with Nostoc in cephalodia (organic Δ = 17 to 25‰, on-line Δ = 16 to 21‰, k0.5 = 388 μ1 · 1−1, Γ = 85 μ1 · 1−1, DIC pool size = 8.5 ± 2.4 nmol · mg−1 Chl). The relative importance of refixation of respiratory CO2 and variations in source isotope signature were considered to account for any variation between on-line and organic Δ. Organic Δ was also measured for species of Anthocerotae and Hepaticae which contain pyrenoids and/or Nostoc enclosed within the thallus. The results of this screening showed that the pyrenoid is correlated with low, more C4-like organic Δ values (Δ = 7 to 12‰ for members of the Anthocerotae with a pyrenoid compared with Δ = 17 to 28‰ for the Hepaticae with and without Nostoc in vesicles) and confirms that the pyrenoid plays a fundamental role in the functioning of the CCM in microalgal photobionts and some bryophytes.

A high frequency restriction fragment length polymorphism (RFLP) at the 3'-end of the pigeon pro alpha 2(1) collagen gene was detected using the restriction endonuclease EcoR1. The distribution of this allelic variant was analyzed in DNA isolated from White Carneau pigeons genetically susceptible to the development of spontaneous atherosclerosis. The atherogenic phenotype in individual pigeons was measured by the determination of total cholesterol and cholesterol ester levels in the celiac focus of the thoracic aorta of adult White Carneau pigeons. Aortic wall cholesterol levels correlated with an increase in lesion size. No correlation, however, was observed between allelic variants of the pigeon pro alpha 2(1) collagen gene and the atherogenic phenotype in White Carneau pigeons suggesting lack of linkage between this allelic marker and the genetic susceptibility to spontaneous atherogenesis. This is the first study of its kind in this animal model and serves to provide a basis for the further analysis of co-segregation of RFLPS in candidate genes to this polygenic phenotype.

A sample of 1,617 12- to 15-year-old boys was classified with respect to the presence or absence of learning disabilities (LD) and interviewed individually concerning family background, school attitude, and self-reported delinquent behavior. Two groups of boys were included in the sample: one of 633 who had been adjudicated delinquent by juvenile courts and a second of 984 who had no records of previous adjudication. The percentages of boys in the delinquent and nondelinquent groups who were classified as learning disabled were 36.5 and 18.9, respectively. In a hierarchical multiple regression analysis, a general self-reported delinquency (SRD) measure was regressed on LD classification, controlling for the effects of potentially confounding background variables. The results indicated that the presence of LD had a small but significant negative relationship with general SRD, fl = o.060. There was a strong positive relationship, however, between the presence of LD and the probability of adjudication (fl = .951) when adjudication status was regressed on LD classification in a logistic regression analysis. These results suggest that learning-disabled youths do not evidence more delinquent behavior than non-learning-disabled youths, but they are more likely to be found delinquent by juvenile courts. (Abstract Adapted from Source: Journal of Educational Psychology, 1981. Copyright © 1981 by the American Psychological Association) Learning Disability Low Intelligence Delinquency Causes Juvenile Delinquency Juvenile Offender Juvenile Male Male Offender Juvenile Development Intellectual Development Early Adolescence Late Adolescence Intelligence-Delinquency Link 09-99

Norfloxacin, a new oral quinolone antimicrobial agent, was shown to have considerably greater activity than nalidixic acid and cinoxacin against sensitive and resistant strains of Enterobacteriaceae. A clinical trial was carried out comparing norfloxacin with amoxycillin in two groups of 20 geriatric patients with complicated urinary tract infection. The cure rate was 95% with norfloxacin and 75% with amoxycillin. Failures of treatment were due to increased bacterial resistance in most cases. Norfloxacin was well tolerated by all patients and no changes were noted in the toxicological assessment. Norfloxacin is a valuable addition to the oral antimicrobial agents available for the treatment of urinary tract infection.

Three simultaneous azo dye coupling reactions and an indigogenic phosphate reaction were compared for their ability to detect chicken intestinal alkaline phosphatases separated in polyacrylamide disc gels. The diazoniums examined, Fast Red TR, Fast Blue RR and Nuclear Fast Red Salt, used sodium alpha-naphthyl acid phosphate as the substrate. Fast Red TR and Fast Blue RR were suitable for the detection of alkaline phosphatases whereas Nuclear Fast Red Salt and the indigogenic phosphate were not. This study shows the necessity for evaluating a stain under the actual experimental conditions.

N-Phthaloylglycylaminocthanol may be prepared in 24% yield by a modification of the Shechan carbodiimide synthesis of peptides of hydroxy amino acids (6). The amino alcohol is characterized as to melting point, solubility in various solvents, the ability to form a derivative with acetic anhydride, percentage of nitrogen, and infrared spectra. In acid solution this compound appears to undergo the aminoacyl shift characteristic of compounds containing an amide linkage and a free hydroxyl group. Attempts to isolated N-glycylaminoethanol by hydrolysis of the phthaloyl derivative with hydrazine hydrate have been unsuccessful. Impure N-phthaloylalanylaminoethanol and N-phthaloylglycylglycylaminoethanol were also synthesized by means of this procedure. Several other methods for synthesizing N-glycylaminoethanol are discussed.

Summary Poxvirus haemagglutinin has been separated into two components by ether/ethanol extraction and also by column chromatography after treatment with 2-chloroethanol. One component, lipid in nature, carried the haemagglutinating activity. The other, a protein termed the antibody blocking component, carried the virus specificity. By the use of techniques applied by others to the study of lipoprotein membranes, poxvirus haemagglutinin of high specificity was reconstituted from the two components. The reconstituted material reacted with antibody to haemagglutinin but not with antibody to a non-haemagglutinating poxvirus. Reconstitution did not take place when either of the two components was replaced by fractions prepared from uninfected tissues or from tissues infected with a non-haemagglutinating poxvirus. Mixed haemagglutinins could be prepared from fractions prepared from different tissues or from different haemagglutinating poxviruses.