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Original Article
Estimating recurrences prevented from using trastuzumab in HER-2/neu–positive adjuvant breast cancer in the United States
Version of Record online: 23 AUG 2010
DOI: 10.1002/cncr.25347
Copyright © 2010 American Cancer Society
Volume 116, Issue 24, pages 5575–5583, 15 December 2010
Additional Information
How to Cite
Danese, M. D., Lalla, D., Brammer, M., Doan, Q. and Knopf, K. (2010), Estimating recurrences prevented from using trastuzumab in HER-2/neu–positive adjuvant breast cancer in the United States. Cancer, 116: 5575–5583. doi: 10.1002/cncr.25347
Publication History
- Issue online: 3 DEC 2010
- Version of Record online: 23 AUG 2010
- Manuscript Accepted: 1 MAR 2010
- Manuscript Revised: 16 FEB 2010
- Manuscript Received: 23 NOV 2009
- Abstract
- Article
- References
- Cited By
- breast cancer;
- trastuzumab;
- prevention;
- recurrence;
- epidemiology
Breast cancer recurrence is associated with significant morbidity, mortality, and cost. Patients with early stage HER2+ tumors are at increased risk of recurrence. The use of trastuzumab for these patients has been shown to reduce recurrences and improve overall survival.
A Monte Carlo simulation was conducted based on Surveillance, Epidemiology, and End Results incidence rates for 2005, United States Census data for 2005, and the results of key trials of the adjuvant use of trastuzumab. Patients included in this analysis had incident, HER2+, stage I to III breast cancer. The number of recurrences that could be prevented with trastuzumab, the cardiac adverse events that might occur, and the associated cost savings were estimated.
Approximately 31,200 women had HER2+ breast cancer in 2005, of whom 7298 would have had a recurrence over the subsequent 5 years despite standard of care adjuvant treatment. If trastuzumab were added to their regimen, 2791 women might have avoided recurrence, and 948 may have had an asymptomatic or symptomatic cardiac adverse event, for a ratio of expected recurrences to cardiac adverse events of 3.2 (95% confidence interval, 1.5-5.9). In economic terms, avoidance of future breast cancer recurrences was associated with lifetime reduction in future direct and indirect costs on the order of $240 million to $1.7 billion.
On the basis of the simulation results, targeting HER2+ tumors with trastuzumab in the adjuvant setting should prevent a significant number of women from recurrence events, with important outcomes for patients, physicians, payers, and society. Cancer 2010. © 2010 American Cancer Society.
Recurrences of breast cancer are associated with significant morbidity, mortality, and cost.1 Women with HER2+ tumors are at higher risk of recurrence than other women, suggesting that the clinical and economic burden is even higher in this subgroup of cancer patients.2-4 Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, Calif) has been shown in multiple studies to reduce recurrences in women with stage I to III HER+ breast cancer who have been appropriately diagnosed and treated.5-7 In addition to demonstrated clinical efficacy, several cost-effectiveness analyses of trastuzumab in the adjuvant setting have found its use to represent an economically attractive value proposition, according to commonly accepted standards.8-12 Taken together, these reports address the important issues of safety, efficacy, and value, however, none of them evaluates the impact on the US population of introducing this new therapeutic option in terms of either the recurrences prevented or the potential associated cost savings.
The purpose of this research was to estimate the annual number of patients in whom recurrence events (local recurrences, distant recurrences, contralateral tumors, and deaths) might be prevented. Typically, the concept of extrapolating results to a population has been focused on understanding risk factors for disease and the effect that eliminating the risk might have on the population. This concept of measuring attributable risk or etiologic fraction has been well documented, albeit the subject of some debate because of the variety of measures and interpretations.13
In this research, we are evaluating the benefit of a beneficial exposure (treatment), rather than the risk, and we are doing so using Monte Carlo simulation techniques rather than the results of any single study.14 Furthermore, we address not only the primary benefit of treatment, but also the primary risk, cardiac adverse events. Finally, we explore the economic impact of prevented recurrence events to society.
HER2+ Breast Cancer Incidence
The Monte Carlo model uses data from the Surveillance, Epidemiology, and End Results (SEER) program as the basis for the simulation, with crude rates and confidence intervals obtained using SEERStat software version 184.108.40.206 Women aged 30 years and older with stage I to III breast cancer were included from the 17 available registries for 2005. The results were stratified by age (30-49, 50-69, and 70+), estrogen receptor (ER) status, progesterone receptor (PR) status, and nodal involvement (0 nodes vs > 0 nodes).
We assumed that patients with missing ER, PR, or nodal status would not be HER2 tested and are excluded from our rate estimates (7%-9% of patients, depending on age). Excluding these patients also minimizes the number of patients who either were diagnosed at autopsy or died very quickly after diagnosis and could not be tested. Furthermore, the model excludes both recurrent patients and incident metastatic patients.
HER2 status
Because HER2 status is not available in SEER, the number of HER2+ patients was estimated as a proportion of the total population within each of the 4 mutually exclusive strata defined by ER and PR status. This was done by applying estimates of the association between HER2 status and both ER and PR status based on a review of the literature. We applied the results from a single, large, population-based study using immunohistochemistry (IHC) for our base case.16 We then applied rates of fluorescence in situ hybridization positivity for the proportion of patients who were 2+ using IHC to reflect current recommendations for HER2 testing.17, 18 Because this is a critical aspect of the simulation, we compared the estimates of HER2+ by each of the ER and PR strata from our base case to those from other studies for validation purposes and found little variation (sensitivity analyses not reported).19-23
Population estimates of HER2+ breast cancer
The resulting incidence rates were applied to the 2005 US female population counts to estimate the number of HER2+ breast cancer cases.24 The estimated HER2+ patient counts were stratified by nodal status, and age according to their distributions in SEER (ie, they did not vary by HER2 status). A recent study suggested that most, but not all, patients (98%) who should be tested for HER2 status are receiving testing, and this is also incorporated into the model.25
Efficacy of Treatment, Recurrence, and Cardiac Adverse Events
Efficacy of treatment
The efficacy rate for trastuzumab was based on 2 studies that compared doxorubicin and cyclophosphamide followed by a taxane versus the same regimen plus 52 weeks of trastuzumab.5, 6 These results are consistent with other reports on the efficacy of trastuzumab in the adjuvant setting.7, 26 The relative risk of recurrence with trastuzumab was considered to be constant across subgroups, and to persist for 5 years.27 After 5 years, no recurrences were assumed to be prevented.
Recurrence events
Recurrence events were defined as local recurrences, distant recurrences, contralateral tumors, and deaths. Overall recurrence rates from the placebo group were stratified by nodal status and pooled across studies. The rate for the trastuzumab group was estimated by applying the pooled hazard ratio to the placebo recurrence rates. The rate of recurrence was assumed to be constant over the 5-year risk period.13 Survival after recurrence was not modeled.
Cardiovascular events
Two studies (National Surgical Adjuvant Breast and Bowel Project B-31 and North Central Cancer Treatment Group N9831) estimated virtually identical proportions of patients experiencing a cardiac event (primarily defined as asymptomatic ejection fraction decline below a threshold or frank congestive heart failure including symptoms of dyspnea with normal activity) based on patients with a maximum of 3 years of follow-up.28-30 Because the B-31 data were recently updated through 5 years and are very similar to the 3-year results, we elected to use the B-31 5-year cardiac data, because it matched the time frame we used to estimate recurrences.30, 31 Whereas the intent-to-treat trial analysis included patients who never received Herceptin because of anthracycline-related cardiac complications, the National Surgical Adjuvant Breast and Bowel Project B-31 analysis of cardiac adverse events excluded them. Therefore, these patients (approximately 7.5%) were also removed from the group considered to be at risk of trastuzumab-associated cardiac adverse events for consistency, and they did not benefit from trastuzumab therapy.28
Costs of Recurrence Events
We searched the literature to estimate the costs attributable to breast cancer recurrence including direct (medical and nonmedical) and indirect (loss income, productivity, and caregiving) costs from a societal perspective. The reference year for the analysis is 2008. Direct medical costs for recurrence events (except death) were adapted from a paper by Stokes et al1; we extracted the 12-month incremental cost of recurrence for women with each event compared with women with no recurrence. These costs were inflated to 2008 dollars using the medical portion of the consumer price index.31 In the study by Stokes et al, most of the recurrence events and costs, particularly for distant recurrence, were incurred in the first year. Therefore, we used the 12-month incremental cost as a proxy for the cost of the recurrence events. In this evaluation, costs of follow-up, including the cost of adverse events, were excluded.
We took 2 approaches to valuing the indirect costs of breast cancer recurrence: 1 excluding the cost of lost years of life, and the other including it. When excluding the cost of early death, we identified published estimates of patient time cost,32 early retirement,33 and lost time from work34 (we could not identify caregiver burden costs associated with recurrence). We assumed that patient time costs were similar for initial and recurrent cancer. Where necessary, we valued hours using national hourly labor rates.35 Finally, we incorporated published variability estimates in all costs to allow for variations in our inputs that reflect both uncertainty and variability.
When including death, we used the societal cost of lost productivity (including caregiver costs) from breast cancer death published by Bradley et al.36 In this study, the lost years of life, and their value in terms of productivity losses, decreases with age. To be conservative, we applied the lowest cost applicable to each of our 3 age groups (eg, the cost from Bradley et al for age 45-49 was used for our 30-49 age group). Furthermore, because not all cancer recurrences lead to death, and because life expectancy after breast cancer diagnosis can take 15 years to return to normal,37, 38 we only applied this cost to the proportion of recurrent patients who were expected to die within 5 years of diagnosis (79%).1 See Table 1 for key data inputs to the model.
|Model Input
|Input (SD or CI)
|Incidence of stage I to III breast cancer in women by age, ER, PR, and nodal status (2005)
|24 stratum-specific estimates
|Efficacy of trastuzumab (hazard ratio)
|0.53 (0.40-0.72)
|Joint analysis,5 BCIRG6
|Proportion HER2+ by ER and PR
|Francis 2007,16 Yaziji 2004,17 Owens 200418
|ER+ and PR+
|0.13 (0.12-0.14)
|ER− and PR+
|0.24 (0.21-0.27)
|ER+ and PR−
|0.25 (0.18-0.32)
|ER− and PR−
|0.35 (0.33-0.38)
|Recurrence rates per patient-year at risk (no trastuzumab)
|Francis 2007,16 Yaziji 2004,17 Owens 200418
|Node negative
|0.041 (0.030-0.056)
|Node positive
|0.083 (0.075-0.091)
|Direct cost of recurrence (2008 $)
|$30,400 ($27,300 to $33,400)
|Adapted from Stokes 20081
|Indirect cost of recurrence (2008 $ in millions)
|Bradley 2008,36 Stokes 20081
|Age, 30-49 years
|$1.43 ($0.68 to $2.66)
|Age, 50-69 years
|$0.40 ($0.16 to $0.81)
|Age, ≥70 years
|$0.09 ($0.07 to $0.11)
Scenario Analyses
Several possible exclusions were considered as part of the scenario analyses. These included the presence of underlying cardiovascular disease based on published prevalence estimates, and the presence of lymph node-negative, small tumors (<1 cm), as suggested by National Comprehensive Cancer Network guidelines.39, 40
More specifically, we defined 3 scenarios selected to represent low and high estimates, with the base case selected to represent something in between. The base case excluded women who would not be tested for HER2, excluded half of women with small (<1 cm) lymph node-negative tumors defined by the National Comprehensive Cancer Network guidelines, and included all recurrence-related events defined in the trials (including second primary and contralateral tumors, and death).
The low estimate made the following changes from the base case: excluded women with severe underlying cardiovascular disease at baseline, excluded all women with small (<1 cm) lymph node-negative tumors defined by the National Comprehensive Cancer Network guidelines, and only included recurrence events (ie, no deaths or contralateral tumors). The high estimate made the following changes from the base case: assumed all patients would be tested for HER2, and included all lymph node-negative patients regardless of tumor size.
Finally, the duration of time over which recurrences were prevented was adjusted to evaluate the importance of this assumption on the final results.
Probabilistic model inputs were included as distributions (mean and variance) to reflect both variability and uncertainty. Normal distributions were used for continuous variables, with binomial distributions used for dichotomous events, and log-normal distributions used for cost data. Relative risks were sampled from a normal distribution on the log scale and transformed back.
When >1 data source was available, variance estimates were created using meta-analysis techniques and weighted according to the inverse of the variance of each estimate.41 Breast cancer incidence rate standard errors were based on estimates provided by SEERStat software. All other estimates were based on values in the literature, with the exception of the costs of productivity losses from Bradley et al,36 which were not reported. The standard deviations for these costs were estimated as proportions of the mean using a proxy. The proxy we selected was the ratio of the mean cost to its standard deviation in our simulation of the cost of recurrence, which excluded the cost of lost years of life (11% to 43% depending on age).
The model was run as a Monte Carlo simulation in Microsoft Excel using the @Risk 5.0 add-in (Palisade Corp., Ithaca, NY). For each iteration of the model, new values from each input distribution were randomly selected, and the results were recalculated automatically. Results taken across multiple iterations were used to estimate the results. Convergence was evaluated by comparing the stability of the key results across different numbers of iterations from 1000 to 10,000. On the basis of the stability of the trial runs, all simulations were run using 5000 iterations and reported as the mean and middle 95% of the empirical distribution, which is referred to as a confidence interval (CI).
The data inputs derived from the literature and used in the model are provided in Table 1. According to the base case estimates, 31,171 women had HER2+ breast cancer in 2005, of whom 29,159 might possibly have been treated given our assumptions. Of these women, 7298 would have had a recurrence over the following 5 years despite current treatment standards. Of these women who recurred without trastuzumab, 2791 would have avoided recurrence with the addition of trastuzumab (see Figs. 1 and 2). Trastuzumab use also would have been associated with an increase of 948 cardiac adverse events, the definition of which includes both symptomatic heart failure and asymptomatic reductions in left ventricular ejection fraction (see Fig. 3). On the basis of these figures, the ratio of expected recurrences to cardiac adverse events is 3.2 (95% CI, 1.5-5.9). This ratio was notably higher for the youngest cohort of women compared with the older 2 cohorts pooled together (7.2 vs 2.7). See Table 2 for ratios and 95% CI by age group.
|Age, 30-49 Years, No. (95% CI)
|Age, 50-69 Years, No. (95% CI)
|Age, ≥70 Years, No. (95% CI)
|Total recurrences prevented
|692 (394-974)
|1348 (763-1901)
|751 (422-1074)
|Cardiac adverse events
|111 (24-202)
|529 (267-809)
|308 (153-470)
|Recurrence prevented to cardiac event ratio
|7.2 (2.6-22.2)
|2.8 (1.3-5.5)
|2.7 (1.2-5.3)
|Economic, excluding lost productivity (death)
|Recurrence cost per patient (excluding death; thousands)
|$77 ($47-$152)
|$107 ($59-$227)
|$35 ($30-$46)
|Total cost (excluding death; millions)
|$53 ($24-$114)
|$144 ($61-$330)
|$27 ($14-$40)
|Economic, including lost productivity (death)
|Recurrence cost per patient (including death; thousands)
|$1,458 ($706-$2,694)
|$427 ($194-$844)
|$119 ($102-$139)
|Total cost (including death; millions)
|$1,009 ($399-$2,008)
|$575 ($217-$1,233)
|$89 ($50-$132)
The cost of recurrence was estimated both overall (Figs. 4 and 5) and separately for each age group (Table 2). The cost of recurrence was substantially lower when the cost of death was excluded. Furthermore, the costs varied across age groups. In the analyses excluding cost of death, because there were no early retirement estimates for women aged 30 to 49 years, the cost was higher for women aged 50 to 69 years. The overall cost was estimated to be $240 million. When death was included, the total recurrence cost was largest in the 30- to 49-year-old age group. In economic terms, avoidance of breast cancer recurrence was associated with savings on the order of $1.7 billion. More than half of this was from events prevented in the 30- to 49-year-old age group.
The base case was adjusted to reflect more conservative and more aggressive assumptions regarding the potential patients who would benefit from therapy. In the low case, the recurrences prevented were fewer (2267; 95% CI, 1288-3188). In the high case, the values were larger (3087; 95% CI, 1748-4356). Finally, when the time horizon was reduced to 4 years, the number of recurrences prevented was smaller (2340; 95% CI, 1331-3285). When the time horizon was extended to 6 years, the results were notably larger (3198; 95% CI, 1802-4502). The corresponding cost estimates for these different scenarios were proportional to the number of recurrences (data not shown).
In the United States, approximately 31,200 women will be newly diagnosed with stage I to III, HER2+ breast cancer each year, based on 2005 data. In the absence of trastuzumab, about 7300 of these women would have a recurrence event even with optimal chemo- and hormonal therapy. Of these, about 2800 women might have been prevented from a recurrence event if trastuzumab had been added to standard adjuvant treatment. This analysis uses 2005 as a proxy; most other years would be expected to be similar, because changes in incidence are relatively slow and would take some time to change these results substantively. Viewed a different way, over the next 25 years, HER2-targeted therapies would have the potential to prevent >55,000 cases of recurrent disease, assuming no substantive changes in the incidence of HER2+ disease. Given the potential for shortages in physician supply in oncology, fewer recurrences will help to move potentially scarce future resources to other patients.42, 43
The corollary to findings is that there are still many ways to improve outcomes, because there are approximately 4500 women who will have recurrences within 5 years despite optimal adjuvant therapy. This translates to approximately 90,000 women over the next 25 years for whom additional improvements in HER2 treatment are needed. Also, as with any therapy, there are risks to treatment. Cardiac adverse events represent the most significant complication associated with trastuzumab, although many of them are reversible to some degree. However, the 3:1 recurrence-to-cardiac event ratio suggests a high benefit-to-risk ratio given the potential improvement of the associated decline in cardiac functioning.
Furthermore, there is some evidence that newer regimens may have lower rates of cardiac adverse events than seen in studies B-31 and N9831.6, 7, 27 In particular, in the Breast Cancer International Research Group study evaluated the efficacy and safety of 52 weeks of Herceptin administered as a component of both an anthracycline-based (doxorubicin/cyclophosphamide/taxane/trastuzumab) and a non– anthracycline-based (cyclophosphamide/taxane/trastuzumab) adjuvant regimen in comparison to doxorubicin/cyclophosphamide/taxane for women with early stage HER2+ lymph node-positive or lymph node-negative cancer. Because the Breast Cancer International Research Group study has shown that cyclophosphamide/taxane/trastuzumab and doxorubicin/cyclophosphamide/taxane/trastuzumab are not statistically significantly different in terms of overall survival at 5 years, these simulation results may reflect a conservative estimate of the cardiac adverse event risk from adjuvant therapy.44
We also used this model to explore economic consequences. Avoidance of breast cancer recurrence can lead to substantial economic savings. Depending on whether the productivity gains (ie, the economic value) from lost years of life are included, this estimate ranges from $240 million to $1.7 billion over the lifetimes of each 1-year cohort of patients. It should be cautioned that appropriately valuing the indirect cost of cancer is not a simple undertaking.45, 46 The cost of cancer is very broad and includes some difficult-to-measure aspects; therefore, the inference from our analyses should not be that these numbers represent the definitive estimate of the value of preventing recurrences. Rather, what is clear from exploring the cost data is that there are significant costs of breast cancer recurrence, most of which accrue from lost years of life. Accordingly, this is the actual value of treatments that can prevent recurrences, particularly those that are associated with high mortality risk, such as HER2+ breast cancer.2-4
Because our purpose was to estimate the number of recurrences and to explore their long-term economic implications, we did not address the cost of treatment. However, at least 3 cost-effectiveness analyses have done so.9, 11, 12 Assuming no missed doses or dose reductions, and including costs for time missed from work, Kurian et al12 estimated, per patient, that 1 year of trastuzumab and cardiac monitoring would cost $72,285 in 2008 dollars, and would yield approximately 1.4 quality-adjusted life-years (QALYs). This would translate to approximately $2.1 billion in total costs and 41,000 QALYs for the women treated in each year. Although these numbers are not directly relevant to our study, they should provide some context for the estimates presented.
As with any model, there are limitations based on the data and assumptions used to construct the base case analyses. In general, we tried to remain conservative (underestimate) where possible. The efficacy of trastuzumab was based on an intent-to-treat analysis. However, crossover from placebo to trastuzumab occurred in 12% of patients, which suggests that trastuzumab efficacy may be underestimated. Also, trastuzumab may reduce recurrences for >5 years, but this is not considered in the model except for the sensitivity analyses. Although the base case does not assume that every woman would be treated, and we conducted scenario analyses to explore alternative base case definitions, it may be that the base case does not capture the current state of treatment. Finally, effectiveness in the real world, may be very different from trial experience, both because healthier patients may have been selected for the trials, and because patients may not adhere as well outside of the trials.
In terms of the economic impact, which excluded the value of lost years of life, we did not include estimates of caregiver costs, and we did not value early retirement in our youngest age group. In the estimate that included lost years of life, we applied no costs to the subset of patients who recurred but did not die within 5 years. This is likely to be conservative, because even long-term survivors are likely to incur some costs, as evidenced by research showing that cancer survivorship is associated with risk of unemployment.47 Furthermore, because we assigned the lowest relevant value for productivity losses in each age group, these are likely to be underestimated.
Although we incorporated uncertainty in our inputs into the model, because our model represents 1 year, we did not address potential changes in the population dynamics. The relationship between HER2 status and ER and PR status may be different by age, or may change over time. For example, there is some indication that recent decreases in breast cancer incidence have been observed in proportionally greater numbers in strongly hormone receptor-positive patients and this trend may not be as strong in the HER2+ population.48, 49 Furthermore, although this model is based on current trial results, there is likely to be improvement in outcomes over time as the treatment of HER2+ tumors evolves. As the SEER program begins to capture HER2 status, and other changes take place over time, this model can be updated to provide more accurate information on the societal implications of treatment.
In terms of interpreting the economic measures, it should be noted that the model does not address any costs of adjuvant treatment, including the costs of treating cardiac (or any other) adverse events. Because of this, these economic results should not be considered to be a net gain for society. Rather, the estimate represents the value of preventing recurrences as a consequence of treatment, regardless of the cost of treatment. From the societal perspective, these savings, realized in a subset of HER2+ patients, could be envisioned as helping to offset costs in the larger population, including screening, diagnosis, testing, treatment, and adverse events. It should be emphasized, however, that because of the nature of the costs considered in this model, the value of preventing recurrences does not directly result in tangible savings that can be immediately invested in the healthcare system.
Regardless of the limitations of this simulation model, the policy implications are clear. The burden of HER2+ disease can be significantly ameliorated with existing targeted therapies. Although this is important, there is also room for more improvement. Consequently, targeting HER2+ tumors in the adjuvant setting could prevent a significant number of women from recurrence events, with important clinical, humanistic, and economic consequences for patients, physicians, payers, and society.
This research was funded by Genentech. Drs. Brammer and Lalla are employees of Genentech.
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- 47Cancer survivors and unemployment: a meta-analysis and meta-regression. JAMA. 2009; 301: 753-762., , , ,
- 48Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008; 100: 1672-1694., , , et al.
- 49Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007; 99: 1152-1161., , ,


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Prestonsburg Carports
Catapult Steel Buildings, LLC
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Olympia Steel Buildings
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Showing1-9 of 9results


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Home > News > University of Minnesota receives $10 million
September 25th, 2006
University of Minnesota receives $10 million
The University of Minnesota Institute of Technology announced today that it has received an anonymous $10 million bequest. The deferred gift will be used to set up a permanent endowment to fund graduate student fellowships in the Institute of Technology, the university's college of engineering, physical sciences and mathematics.
University of Minnesota
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Hey horse lovers, challenge your child's imagination with lovely animal coloring games in Horse Coloringpony horses, horse games, horse pictures, horse images
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Visit our other Wisconsin Historical Society websites!
Refine or narrow your results by clicking any term in the gray boxes below.
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Date: 1931-7-02
County: Dane
City: Madison
Date: 1873 ca.
Description: Main Street, with its dirt, ruts, cows (and presumably manure), but wide enough for easy hitching of wagons and teams.
Date: date unknown
Description: View across field towards the Kipp Company building.
Date: 1912-12
Description: Sanborn Map of Sun Prairie. The map highlights the public and parochial schools, the exhange, and church buildings, etc.
Date: 1954-11-25
Description: Farm equipment department at the new Sears store, located at 1101 East Washington Avenue.
Date: 1931-7-07
Date: 1915 ca.
Description: Exterior of University of Wisconsin-Madison College of Agriculture Hiram Smith Hall or Dairy Hall. On the left is a large chimney.
Date: 1908 before
Description: Exterior view of landscaped stairway entrance to the University of Wisconsin-Madison College of Agriculture.
Date: 2010
Description: A man drives a tractor on John Nolen Drive along Lake Mendota with the Wisconsin State Capitol in the distance. He is on his was to a Red Power venue held...
Date: after
Description: Exterior view of the University of Wisconsin Stock Pavilion at the College of Agriculture.
Date: 1905 ca.
Description: A man stands with a horse near a small barn. A buggy and wagon are parked nearby. There are two small sheds or outhouses near a garden plot and a haystack...
Date: 1979
Description: Two people take a break at an unidentified Rennebohm Drug Store restaurant: the woman enjoys a cup of coffee, her companion works on a crossword puzzle.
Date: 1957-02-05
Description: Three members of the Homemaker's Chorus who sang during the annual University of Wisconsin's Farm and Home Week. From left to right are Mrs. Henry Peters a...
Date: 1960-05-22 ca.
Description: View of a newly planted field on a hillside. The edge of the field is shaded by a tree-lined ridge.
Date: 1921-2-17
Date: 1964-05-30 ca.
Description: Landscape view from field of a rolling countryside. A small cheese factory resides on a slope, with a tree, a windmill, two cars and a tractor near an outb...
Date: 1945-05-15
Description: Governor Goodland signing a bill (probably, Ch 131, Laws of 1945 relaxing the state's food sanitation law and easing animal slaughter on family farms) with...
Date: 1948-04-09
Description: Farmall Tractor photographed outside the Kupfer Foundry and Iron Works, 101 Waubesa Street. Photograph taken for R.L. Kulzick advertising agency.
Description: Winter scene with a path through snow at University of Wisconsin-Madison College of Agriculture. Two buildings are on either side of the path. The horse ba...
Date: 1873
Description: A map of the township of Primrose from the "Atlas of Dane County."
If you didn't find the material you searched for, our Library Reference Staff can help.
Call our reference desk at 608-264-6535 or email us at:
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application architecture leader jobs near Stamford, CT
Refine your searchClear Filters
Date Added
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AVP, IT Mobile Project Manager (L11)
Synchrony Financial - Stamford, CT
Project Manager/ Scrum Master for front end native development teams and web services teamsWork with business teams to shape native app business requirements...
Solution Architect
Boehringer Ingelheim - Ridgefield, CT
Experience in application architecture, application development, database. Define and implement a application architecture road map....
IT Security Architect
ONIT, Inc. - Westport, CT
Practices and methods of IT strategy, enterprise architecture and security architecture. Information Systems Security Architecture Professional....
SharePoint Technology Architect
Advanced Programming Group - Stamford, CT
Work closely with IT and business leaders to implemented SharePoint solutions. Lead SharePoint architecture and design activitiesMock ups and proof-of-concepts...
Enterprise Architect
Dealertrack - Lake Success, NY
Bring Enterprise Architecture knowledge into architecture and engineering teams while exposing project and solution related architectural issues to the...
SAP Solution Architect(FICO)
INDSOFT - Wilton, CT
Support Design and Architecture for Finance and Procurement solutions. MBA or Master's Degree Overall 10+ years of Information technology experience 8+ years of...
SharePoint Architect
Econosoft - Stamford, CT
Lead SharePoint architecture and design activitieso Mock ups and proof-of-concepts targeting new enterprise SharePoint implementations.o Monitor and size...
IT Director
Chateaux Software - Greenwich, CT
Managing the deployment, maintenance, upgrade, security, and support of all IT systemsResearching and staying up to date on new technology, and how it could be...
Director Systems Intelligence Center of Excellence
Xylem, Inc. - Port Chester, NY
Develop materials to market Systems Intelligence innovation, infrastructure, architecture, roadmap, applications, processes, security and reliability....
FICO Solution Architect
Indsoft, Inc. - Wilton, CT
This individual will Support Design and Architecture for Finance and Procurement solutions. The Solution Architect is the key contributor in defining solution...


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Palo Alto About us: Syapse is a growing team of smart, passionate people committed to transforming the practice of medicine. Today, with the help of Syapse, doctors are harnessing complex clinical and genomic data to improve and extend the lives of cancer patients. Built on a5/16/2016 Palo Alto, CA Save This Job
DEPARTMENT Information Services CITY Los Angeles, CA TYPE Full-Time What you?ll do As the Director of Enterprise Applications, you will govern Belkin?s entire portfolio of applications and IT services; which includes all global financial, order processing, product lifecycle5/16/2016 Los Angeles, CA Save This Job
Palo Alto About us: Syapse is a growing team of smart, passionate people committed to transforming the practice of medicine. Today, with the help of Syapse, doctors are harnessing complex clinical and genomic data to improve and extend the lives of cancer patients. Built on a5/16/2016 Palo Alto, CA Save This Job
Sales New York or Remote/any location , United States Apply Description The National Sales Director will expand and increase Phreesia?s presence and use in large, multi-specialty practices and Integrated Delivery Networks throughout the US. This individual is expected to5/15/2016 New York, NY Save This Job
We?re looking for an exceptionally hands-on Account Director who is passionate about advertising, well versed in digital media buying and hungry to build a ground-up business with us. Responsibilities Build and maintain a robust sales pipeline Consultative enterprise selling to5/11/2016 New York, NY Save This Job
This position is located in Columbus, OH. About Us: Major League Gaming (MLG) (www.majorleaguegaming.com) is the world's largest eSports organization with millions of LIVE viewers, fans and competitors around the globe. MLG enables gamers to compete, improve their skills, and5/10/2016 Columbus, OH Save This Job
Location:Boston, MA Job Code:703 # of Openings:1 Description DataXu?s vision is to make marketing better using data science. The world?s top brands and agencies partner with DataXu to better understand and engage their customers across all available media formats, devices,5/8/2016 Boston, MA Save This Job
Responsibilities / Opportunity The role of Director, Advertising Sales in the Midwest will be responsible for meeting / exceeding advertising revenue quota, identifying new business opportunities, cultivating long-term strategic partnerships and increasing marketplace5/3/2016 Chicago, IL Save This Job
Responsibilities / Opportunity The Director, HCP Advertising Sales will be responsible for meeting / exceeding advertising revenue quota, identifying new business opportunities, cultivating long-term strategic partnerships and increasing marketplace visibility/stature within5/3/2016 New York, NY Save This Job
WEST COAST AND NEW YORKSALESFULL APPLY TO THIS JOB ABOUT AHALOGY Ahalogy is The Marketer?s Solution for Pinterest - the only SaaS company that delivers Pinterest optimization for brands. We provide a turnkey solution for marketers to ?win? on Pinterest through our proprietary4/30/2016 New York, NY Save This Job
NEW YORK, NYPRODUCT FULL-TIME Hi! Thanks for checking us out. It?s a pleasure to meet you... Offerpop's Visual UGC Marketing SaaS platform empowers brands to encourage and leverage user generated content at every stage of the buyer journey, improving marketing performance.4/26/2016 New York, NY Save This Job
Type Full-time Company Anark is the leading provider of engineering and manufacturing software for manufacturers embracing the power and efficiency of PLM driven 3D Model Based Enterprise (MBE) and Visual Communication applications. Anark helps market leaders such as General4/25/2016 Boulder, CO Save This Job
Chicago Who We Are Opternative is a healthcare technology company building something bigger than a great application; our team has created the online eye exam that science never thought possible. Opternative is looking for more than just skilled and talented individuals. We are4/24/2016 Chicago, IL Save This Job
Sales Washington, D.C., DC Venafi is a rapidly growing cyber security organization which helps our customers prevent trust based attacks. Venafi is widely recognized as the leader in managing, securing and protecting cryptographic keys and digital certificates that every4/24/2016 Washington, DC Save This Job
Job Description Director, Business Development - (01742) Description Summary: Gemalto Identity and Data Protection (IDP)?s technology partners are a critical component of how we go to market to reach enterprise customers. The Business Development Manager is responsible for4/24/2016 CA Save This Job
All times are in India Standard Time. ID 2015-2056 Job Location US-PA-Plymouth Meeting Posted Date 12/4/2015 More information about this job: Overview: Accolade is the leading technology-enabled consumer healthcare engagement services company for large employers, payers and4/23/2016 Plymouth Meeting, PA Save This Job
Req No.2016-2027Job LocationsSouth San FranciscoDepartmentAccounting/Finance MORE INFORMATION ABOUT THIS JOB Collaborative, assertive, flexible, passionate, driven, inspired. These aren?t just nice words, they?re the start of every great Fluidigm career. We are a growing5/22/2016 South San Francisco, CA Save This Job
Location: Santa Clara, CA Type: Full Time or Short-Term Contract Apply Virsec is looking for a Director of Product Management. Want to be on the front lines of advancing a powerful new cyber defense technology? Do you see yourself in a role that will help reshape the world of5/17/2016 Santa Clara, CA Save This Job
DescriptionWe are looking for a Director/Sr. Director of Marketing Strategy & New Opportunities to help GREE become the most player centric gaming company in the world. If you are someone who can see the potential in games before they even start, gets fired up to channel userSan Francisco, CA Save This Job
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Force India draw a blank in BahrainSahara Force India finished without points in the Formula One Bahrain Grand Prix with Nico Hulkenberg and Sergio Perez crossing the line in a disappointing 15th and 16th place here today. Contacts in the early part of the 57-lap race pushed ... Business Standard, 2 months ago
Motor racing-Force India waiting on 2017 rules in EU complaint - Sify, 4 weeks ago
Perez gives Force India 4th podium finish - Rediff.com, 1 month ago
523 images for bahrain formula
Bahrain GP: Mercedes' Rosberg wins second consecutive race; Raikkonen, Hamilton complete podium
Mercedes driver Nico Rosberg became the eighth man in Formula One history to win five consecutive races with a victory at the Bahrain Grand Prix The post Bahrain GP: Mercedes' Rosberg wins second consecutive race; Raikkonen, Hamilton complete podium ...First Post.com, 2 months ago Nico Rosberg romps untroubled to fifth win in a row at Bahrain F1 Grand Prix| Reuters First Post.com, 2 months ago Bahrain Grand Prix: Rosberg romps to fifth win in a row Rediff.com, 2 months ago Rosberg rules, Vettel fails to start The Telegraph, 2 months ago
Bahrain GP: Hamilton reprimanded for reversing in pitlane
Formula One champion Lewis Hamilton was reprimanded at the Bahrain Grand Prix on Saturday for reversing his Mercedes in the pitlane moments after qualifying on pole position ahead of team mate Nico Rosberg. Stewards said in a statement that the Briton had escaped a more severe sanction "due to the fact that no clear instruction was given to the driver on where he should park the car after qualifying". Hamilton told reporters he had slowed down, well inside the speed limit, before he entered the ...Rediff.com, 2 months ago F1 2016: Hamilton smashes lap record and takes Bahrain GP pole First Post.com, 2 months ago Formula One's Hamilton smashes record to grab Bahrain pole Reuters, 2 months ago Hamilton beats Rosberg to Bahrain pole position Rediff.com, 2 months ago
Formula One: Ferrari end final Bahrain GP practice on top
Vettel lapped the Sakhir Circuit in a best time of one minute 31.683 seconds, 0.040 faster than team mate Kimi Raikkonen on the supersoft tyres. It was the first time this season that any driver from outside the Mercedes pairing of Nico Rosberg and triple ...India Today, 2 months ago
Nico Rosberg wins Bahrain Grand Prix
Nico Rosberg claimed his second win of the new Formula One season after capitalising on a first-corner collision involving Lewis Hamilton. Rosberg, winner of the season opener in Australia a fortnight ago, got the better of a slow-starting Hamilton to snatch ...MSN India, 2 months ago Nico Rosberg wins manic race at Chinese GP Business Standard, 2 months ago
Hamilton looks to challenge teammate Rosberg in 'favourite' Shanghai
IMAGE: Mercedes F1 driver Lewis Hamilton poses for a drivers portrait before the Australian Formula One Grand Prix in Melbourne on Thursday. Photograph: Jason Reed/Reuters. Lewis Hamilton has had more success in Shanghai than any other Formula One driver, which makes Sunday's Chinese Grand Prix the ideal location for the triple world champion to end Mercedes teammate Nico Rosberg's winning streak. While Rosberg has started the season with a perfect 50 points from two races, and a run of five ...Rediff.com, 2 months ago Mercedes' F1 driver Rosberg's name features in Panama Papers Rediff.com, 2 months ago Chinese Grand Prix: Hamilton hit with five-place grid penalty Rediff.com, 2 months ago Rosberg keeps his sizzling run going in desert Deccan Herald, 2 months ago
Vettel blasts 'circus' nature of F1's new qualifying format
Image: Ferrari's Formula One driver Sebastian Vettel. Photograph: Laszlo Balogh/Reuters. Four-time world champion Sebastian Vettel has joined the bandwagon of drivers opposing the newly proposed aggregate qualifying format of the Formula One. According to the latest qualifying format, a driver's two best laps in each of the three knockout sessions will be combined in order to determine the grid position. Meanwhile, the 90-second qualifying format that saw the drivers get eliminated one ...Rediff.com, 2 months ago Vettel out before the start in Bahrain Rediff.com, 2 months ago F1 to return to 2015 qualifying format Rediff.com, 2 months ago 'Ferrari haven't shown what they are able to do yet' Rediff.com, 2 months ago
Green light with a rider
Fernando Alonso has been provisionally cleared to compete in Sunday's Chinese Formula One Grand Prix after being ruled out of the previous race in Bahrain due to injuries sustained in a crash in Australia last month. The governing International Automobile ...The Telegraph, 2 months ago I feel 100 percent, says Alonso after clearance to race at Chinese Grand Prix Rediff.com, 2 months ago Alonso taking nothing for granted before China medical Rediff.com, 2 months ago
F1 has learnt a lesson: Claire
Formula One learned a lesson from the qualifying fiasco that overshadowed the opening races of the season in Australia and Bahrain, Williams deputy team principal Claire Williams said on Monday. "I think that we have learned that we need to take more time to ...The Telegraph, 2 months ago
Formula One bosses disagree on qualifying, compromise proposed
'We haven't reached the conclusions on how we want to continue yet' IMAGE: F1 supremo Bernie Ecclestone, Red Bull Racing Team Principal Christian Horner, and FIA President Jean Todt walk out after their meeting ahead of the Bahrain Formula One Grand Prix. Photograph: Clive Mason/Getty Images. Formula One teams and stakeholders failed to agree a fix for the sport's failed new qualifying format at the Bahrain Grand Prix on Sunday and agreed instead to go away and consider a ...Rediff.com, 2 months ago
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Toronto Raptors' DeMar DeRozan (10) grabs a rebound against Cleveland Cavaliers' Tyler Zeller and teammate Amir Johnson (15) in a game Tuesday in Cleveland. (AP Photo/Mark Duncan)
Cleveland Cavaliers guard Kyrie Irving (2), forward Alonzo Gee (33), center Tyler Zeller (40) and shooting guard Dion Waiters (3) react as forward Tristan Thompson, not shown, misses two free throws in the fourth quarter against the Boston Celtics in Boston, Wednesday. The Celtics won 103-91. (AP Photo/Elise Amendola)
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DETROIT: Rajai Davis ended Friday night's game in Detroit with a running, juggling, game-winning catch in center field that resulted in a double play and plenty of confusion for both teams.


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UK-based Seabrook Crisps Ltd has invested £1.5m in developing four new flavours of crisp, each with 90 per cent less salt.
The new product, called Goodbye salt, Hello flavour, will be available in Jacket potato with Mediterranean tomato & herbs; Jacket potato with tomato ketchup; Jacket potato with caramelised onion and Jacket potato with creamy butter flavours.
The range is expected to be on the shelves of major retailers by February 1.
John Tague, the expanding company's managing director, told Telegraph & Argus: "We start manufacturing on January 19. The first deliveries to customers should arrive by January 24.
"We are looking to sell 100 million bags in the first year, so it's good news for manufacturers who supply our bags, cartons, oil, flavours and potatoes, and the transport company that will be delivering it all."
A further £750,000 will be spent in targeted advertising in print media, particularly big-selling women's magazines.
"Our market research is telling us there is a whole load of consumers who want to eat crisps but with less salt.
"Majority purchasers of the new brand, which we think is unique, are likely to be female because most females do the weekly shop. So, initially, we will be targeting women and then go out to men over the next 12 months," John added.
The brains behind the new snacks is Seabrook chairman and chief executive Ken Brook-Chrispin.
He said: "The passion and commitment for accomplishing what is, quite frankly, a massive milestone in our industry, was our response to consumer demand for a reduced salt crisp with great taste.
"I'll admit, it has been no mean feat for us. We have undertaken huge amounts of development and research to finally create crisps which live up to our reputation for making the ultimate, tasty crinkle-cut crisps, while enabling the nation to continue its obsession with the humble potato snack and reduce its salt intake."
"Goodbye salt, Hello flavour represents a significant investment of more than £1.5 million. We have high hopes for this unique range in maintaining Seabrook as Britain's fastest-growing crisp brand."
Potato Business @potatobusiness
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AHDB and CEJA Comment on Vote to Leave EU #Brexit https://t.co/seLg19CxXK https://t.co/CkwUByCsCM
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|Sep 14th 2016 - Sep 15th 2016
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Matt Borlenghi Celebrity Watchlist
Video ClipsSee all »
Matthew Borlenghi on what's sexy!00:33 — TV Guide's Michael Ausiello interviews Matthew Borlenghi of All My Children.|Matt Borlenghi|All My Children|Michael Ausiello|TV's Sexiest Stars
Kelly Ripa and Co-Stars Recall Her Time on 'All My Children'It s fitting that Kelly Ripa made her All My Children debut on Thanksgiving Day in 1990. After all, the fan-favorite actress ha (more…)
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Al is thrilled when his childhood love (Debra Engle) asks his help against a young tough who's targeting her convenience store. Matt Borlenghi. Jackie: Kimberly Paige. Ray Ray's Girlfriend: Skye Bassett. Jefferson: Ted McGinley. Marcy: Amanda Bearse. Al: E (more…)
As they await eviction from a Miami hotel, four retired mobsters try to scare off the other residents by making them an offer they can't refuse. Burt Reynolds, Richard Dreyfuss. Donatelli: Dan Hedaya. Donato: Seymour Cassel. Det. Neal: Carrie-Anne Moss. Fe (more…)
Alan Thicke plays a wealthy man, and Nicole Eggert is the woman who uses him after her boyfriend starts dating Kelly. Tom: Matt Borlenghi. Maria: Terri Ivens. George: Phill Lewis. Jackson: Chris Young. Kelly: Christina Applegate.
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The Last Ship9:00 pm | TNTI'll Watch194 Watching
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June 23, 2016
Tryout Candidates Named for U.S. Women' s Team
US Lacrosse has named 105 players that have been selected to try out for the 2016-17 U.S. Women?s National Team. Tryouts will be held from Aug. 5-7 at the national team training center at US Lacrosse headquarters in Sparks, Md.
June 21, 2016
Oregon's Dowd: 'Let the Players Decide the Game'
What is Katrina Dowd's plan for Oregon women's lacrosse? LM's Megan Schneider caught up with Ducks' new head coach for a Q&A.
June 17, 2016
The New Elite: Iris Williamson and Joey Coffy
Penn's Iris Williamson and Cornell's Joey Coffy busted all sorts of stereotypes while earning first team All-Ivy League honors this season.
June 16, 2016
Cummings, Treanor Renew Friendly Rivalry in UWLX
The friendly rivals last met only two weeks earlier when Taylor Cummings' Maryland team beat Kayla Treanor's Syracuse squad in the NCAA tournament semifinals. Now, they are writing a new chapter in their careers with the UWLX.
June 15, 2016
Oregon Hires Katrina Dowd as New Head Coach
With Pac-12 and NCAA championship aspirations, the Ducks made a big splash Wednesday, hiring North Carolina assistant Katrina Dowd as its new women's lacrosse coach.
June 13, 2016
Rules Committee Recommends Three Seconds to be Major Foul
Due to unintended consequences, the NCAA Women?s Lacrosse Rules Committee, chaired by Virginia coach Julie Myers, recommended three-second violations return to being major fouls for 2017. Plus, it recommends a free position experimental rule.
June 10, 2016
Six College Graduates Join UWLX Rosters After Final Four
Following the NCAA final four on Memorial Day weekend, six seniors joined UWLX rosters, including three-time Tewaaraton winner Taylor Cummings.
June 8, 2016
LM's Division I Women All Americans, Players of the Year
North Carolina, the 2016 Division I champion, leads Lacrosse Magazine's All-American Team with three selections, while coach Jenny Levy is named LM's Coach of the Year.
June 8, 2016
Straight Up: 2016 in Review
In this season's new LaxMagazine.com series, Brian Schneider and Sheehan Stanwick Burch take a look back on the best and the worst of the 2016 season.
June 7, 2016
UNC's Markison Makes Her Mark in NCAA Final
The biggest moment in North Carolina's 13-7 dethroning of Maryland in the NCAA championship game? You probably missed it. Devin Markison's family and teammates certainly did not.
June 6, 2016
Early Look: DI Women Top 20 for 2017
Can Maryland bounce back from graduating three-time Tewaaraton winner Taylor Cummings? How will Syracuse recover from losing eight starters? Should 2017 be the year of the Seawolves?
June 6, 2016
IWLCA Names 2016 Players of the Year by Position
Ellie DeGarmo (Princeton), Kayla Treanor (Syracuse), Alice Mercer and Taylor Cummings (Maryland) captured DI positional honors as the IWLCA named its Players of the Year for 2016.
June 3, 2016
Third Time's the Charm for All-Time Great Taylor Cummings
Maryland senior Taylor Cummings made history Thursday night, becoming the first-ever three-time recipient, male or female, of the Tewaaraton Award.


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Contact Information
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Sire pointing Prairie chickens in Kansas at two years old, backed by Lightning Joe.
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This review is from: Three (The Pankhearst Singles Club Book 3) (Kindle Edition)
Three very different stories about relationships. The first, The Big Toe, puts all the squirmingly embarrassing uncertainties of people trying to strike up a relationship into words. Thanks heavens that doesn't normally happen! Hilarious and so true!
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UPDATE: Done. The Minnesota Wild have signed Brett Clark to a prorated $900,000 contract. But don't expect the 36-year-old defenseman to see game action right away.
Links from around the rink for April 20
433dDoug Mittler
Links from around the rink for April 6
447dDoug Mittler
Links from around the rink for March 23
461dDoug Mittler
What's next: Minnesota Wild
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Captain America: Proud member of the Avengers, but heâs a man out of time, frozen for decades and unaccustomed to modern life. Can the Sentinel of Liberty learn to fight alongside heroes 60 years younger than himâ¦and why does Cap feel a strange connection to the man named Korvac? Ben McCool (Choker) brings you an epic tale ten centuries in the making!
"Justice League": Exploring How Superman Returns (Again)
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AMC Renews "Preacher" for Season 2
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In addition to the bags that Warner Bros. is offering at Comic-Con this year, they're also bringing back the hotel room keys that they did at last year's con. A total of 29,000 branded room keys, designed to promote DC Comic's digital comics application, Batman: Under the Red Hood, V, Smallville and Supernatural, will be distributed at 36 participating hotels throughout the San Diego area during the week of the Con. You can find more details here, and check out additional key artwork after the jump.
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